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    Eleni Mylona

    Introduction: The aim of the present study was to investigate the distribution of both lymphatics and blood microvessels in invasive breast carcinomas and the clinicopathological and prognostic significance of their density and size... more
    Introduction: The aim of the present study was to investigate the distribution of both lymphatics and blood microvessels in invasive breast carcinomas and the clinicopathological and prognostic significance of their density and size related parameters as well as their correlation with the proliferative potential of the tumor and VEGF-C and -D expression. Methods: Both single and double immunohistochemistry were applied on a series of 146 paraffin-embedded breast tissue specimens to detect VEGF-C and -D as well as lymphatics and blood microvessels, respectively. Computer-assisted morphometry was performed to evaluate the blood and lymphatic vessel density (BVD and LVD respectively) as well as various vascular size related parameters. Results: Lymphatics were detected within the stroma at the tumor border, while blood vessels were located in both the interior of the tumor mass and peritumor stroma. BV major axis, minor axis and perimeter inversely correlated with ER (p=0.011, p=0.023 and p=0.008 respectively), while LV major axis, minor axis and the perimeter inversely correlated with tumor nuclear grade (p=0.045, p=0.037 and p=0.032 respectively) and topoisomerase IIalpha (p=0.015, p=0.024 and p=0.045 respectively). The same LV parameters were found to positively correlate with cancerous VEGF-C (p<0.0001, p=0.092 and p=0.012 respectively) and VEGF-D in the stromal fibroblasts surrounding neoplastic cells (p=0.011, p=0.041 and p=0.026 respectively). High BVD exerted an unfavorable impact on both disease-free (p=0.021) and overall survival (p=0.031) of the patients. High LVD correlated with poor disease-free and overall survival only in the subgroup of patients with ER-negative tumors (p=0.056 and p=0.0312 respectively). Conclusion: These findings, for the first time, correlate lymphatic size with tumors of limited proliferative potential and higher nuclear differentiation. Moreover, they suggest that VEGF-C and -D expression influence lymphatic size rather than being involved in the increase of lymphatic vessel number.
    Background: Vascular endothelial growth factor-C (VEGF-C) has been associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis and was reported to have an anti-apoptotic and proliferative role. Materials and... more
    Background: Vascular endothelial growth factor-C (VEGF-C) has been associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis and was reported to have an anti-apoptotic and proliferative role. Materials and methods: An immunohistochemical study was applied to 123 specimens of bladder urothelial carcinoma (BUC) to detect VEGF-C and investigate its clinicopathological and prognostic value. VEGF-C-immunostained BUC specimens (123) were statistically correlated with histological grade and stage, patient overall survival and immuno-expression of Ki-67 and bax proteins. Results: VEGF-C immunopositivity (27/123 BUCs, 22.0%) was inversely correlated with tumor stage and bax immunoexpression (p = 0.007 and p = 0.032, respectively). VEGF-C-positive BUCs tended to have better prognosis (univariate analysis). Conclusion: VEGF-C might be associated with an anti-apoptotic phenotype. Our controversial results regarding patient survival suggest that the role of VEGF-C in BUC progression and prognosis remains to be clarified.
    Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcriptional factor that regulates the transcription of various target genes. Our purpose is to investigate the clinicopathologic and prognostic... more
    Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcriptional factor that regulates the transcription of various target genes. Our purpose is to investigate the clinicopathologic and prognostic significance of PPARgamma expression in human urothelial bladder cancer (BUC). Immunohistochemistry was applied in 117 paraffin-embedded specimens of human BUC to detect the proteins PPARgamma and Ki67. The image analysis method was used for the evaluation of the immunohistochemical staining. PPARgamma protein was localized in the nuclei of the malignant cells. Its expression was inversely associated with the stage of BUCs (p&amp;lt;0.001), tumor grade (p=0.007) and the expression of the proliferation marker Ki67 (p=0.015) while it was found to exert a favorable effect on patients&amp;#39; overall survival (p=0.001). The findings of the present study suggest that in BUC, PPARgamma expression can identify patients with a better prognosis who suffer from more differentiated, non-invasive tumors, of a low proliferative potential.
    Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin... more
    Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin embedded tissue specimens from 111 sporadic, invasive breast carcinomas to detect the expression of the proteins BRCA1, ER, PR, erbB2, p53 and Ki67. BRCA1 protein was detected in the nuclei and the cytoplasm of the tumor cells. Nuclear BRCA1 immunoreactivity showed no relation with the classic clinicopathological markers and the expression of cerbB2, p53 and Ki67. Reduced expression of nuclear BRCA1 protein was found to exert an independent favorable impact on both the overall and relapse-free (RF) survival of the patients (p=0.019 and p=0.043, respectively). Cytoplasmic BRCA1 was associated with none of the classic histomorphological indices, except from the lymph node metastasis, with which its relation was found to be inverse (p=0.05), prolonging the RF survival of the patients (p=0.05). Our findings suggest that BRCA1 protein depicts different prognostic significance, according to its subcellular distribution. Nuclear detection of the protein was associated with a worse prognosis, while the cytoplasmic one was related to fewer recurrences as a result of fewer lymph node metastases.
    Objectives.Vascular endothelial growth factors A and B (VEGF-A and VEGF-B) play a major role in angiogenesis and activate VEGF receptor 1 (VEGFR-1). However, the clinicopathologic and clinical value of VEGF-B and VEGFR-1 in invasive... more
    Objectives.Vascular endothelial growth factors A and B (VEGF-A and VEGF-B) play a major role in angiogenesis and activate VEGF receptor 1 (VEGFR-1). However, the clinicopathologic and clinical value of VEGF-B and VEGFR-1 in invasive breast carcinoma remains unclear.
    Contains fulltext : 107754.pdf (publisher&#39;s version ) (Open Access)ABSTRACT: INTRODUCTION: Monosodium urate monohydrate (MSU) crystals synergize with various toll-like receptor (TLR) ligands to induce cytokine production via... more
    Contains fulltext : 107754.pdf (publisher&#39;s version ) (Open Access)ABSTRACT: INTRODUCTION: Monosodium urate monohydrate (MSU) crystals synergize with various toll-like receptor (TLR) ligands to induce cytokine production via activation of the NOD-like receptor (NLR) family, pyrin domain-containing 3 (NLPR3) inflammasome. This has been demonstrated in vitro using human cell lines or monocytes of healthy volunteers. In the present study, we have investigated the effect of MSU crystals and of their combination with TLR ligands in peripheral blood mononuclear cells (PBMC) of patients with gout. METHODS: PBMCs from 18 patients with primary gout and 12 healthy donors were exposed to MSU crystals in the presence or absence of saturated fatty acid C18:0 (free fatty acid, TLR2 ligand), palmitoyl-3-cystein (Pam3Cys, TLR1/2 ligand) and fibroblast stimulating factor-1 (FSL-1, TLR 2/6 ligand). Production of IL-1beta, IL-6, IL-8, IL-17 and tumor necrosis factor alpha (TNFalpha) was determined...
    &lt;b&gt;Copyright information:&lt;/b&gt;Taken from &quot;Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in invasive breast carcinoma: Relation to tumor phenotype and clinical outcome&quot;Breast Cancer... more
    &lt;b&gt;Copyright information:&lt;/b&gt;Taken from &quot;Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in invasive breast carcinoma: Relation to tumor phenotype and clinical outcome&quot;Breast Cancer Research 2006;8(5):R57-R57.Published online 10 Oct 2006PMCID:PMC1779495. The graphs show the effect of tissue inhibitor of metalloproteinases (TIMP)-3 expression on patient recurrence-free and disease-specific overall survival (log-rank test).
    &lt;b&gt;Copyright information:&lt;/b&gt;Taken from &quot;Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in invasive breast carcinoma: Relation to tumor phenotype and clinical outcome&quot;Breast Cancer... more
    &lt;b&gt;Copyright information:&lt;/b&gt;Taken from &quot;Expression of tissue inhibitor of matrix metalloproteinases (TIMP)-3 protein in invasive breast carcinoma: Relation to tumor phenotype and clinical outcome&quot;Breast Cancer Research 2006;8(5):R57-R57.Published online 10 Oct 2006PMCID:PMC1779495. The micrographs show tissue inhibitor of metalloproteinases (TIMP)-3 in the cytoplasm of a lobular carcinoma , both the cancer cells and peritumoral stroma of a ductal carcinoma , carcinoma and normal epithelium . Envision/horseradish peroxidase staining; original magnification ×200.
    Data on the clinical features and outcomes of COVID-19 patients from countries with low disease burden are rare. Greece, however, presented a low burden of COVID-19 disease during the first pandemic outbreak. This is a retrospective study... more
    Data on the clinical features and outcomes of COVID-19 patients from countries with low disease burden are rare. Greece, however, presented a low burden of COVID-19 disease during the first pandemic outbreak. This is a retrospective study of COVID-19 hospitalized patients in Greece. Clinical data were extracted from medical records using univariable and multivariable logistic regression analysis to assess the factors associated with ICU admission and in-hospital death. Eighty five patients were included in this study, 49 (57.7%) male with median (25th-75th) age 60 (49-72) years old. Sixty-one (72%) of them had at least one comorbidity with hypertension being the most common (45,6%). More than half (56%) had severe or critical disease, 20% required ICU care (14% received invasive ventilation) and 10.7% died. Solid tumor (p=0.021) and NEWS score (p=0.048), thrombocytopenia (p=0.036) or involvement of all lung fields in chest x-ray (p=0.002) on admission were independent risk factors o...
    Kisspeptins, which are derived from the gene KISS1, supress tumor progression. We intended to investigate the production of KISS1 and its receptor (KISSR) in gastric cancer. The expression of KISS1 and KISS1R in both normal and cancer... more
    Kisspeptins, which are derived from the gene KISS1, supress tumor progression. We intended to investigate the production of KISS1 and its receptor (KISSR) in gastric cancer. The expression of KISS1 and KISS1R in both normal and cancer tissue was examined with immunohistochemistry in tissue specimens of 40 cases of gastric adenocarcinoma. KISS1 expression in normal gastric mucosa was much higher than in malignant mucosa. KISS1 expression was higher in early stages (stage I or II) than in advanced stages (stage III or IV), in tumors with intestinal histological type than in those with diffuse histological type, in tumors without lymphovascular invasion than in those with and in cancers of older patients (≥70 years) than in younger patients. No significant differences were found regarding other clinicopathological parameters. There was no KISS1R expression in cancer tissues, while only low levels of KISS1R were detected in normal gastric epithelium. KISS1 expression is decreased during...
    Cells with distinct phenotypes and stem cell-like properties have been reported to exist in breast cancer. The aim of the present study was to investigate the clinicopathologic and prognostic significance of the CD44(+)/CD24(-/low) and... more
    Cells with distinct phenotypes and stem cell-like properties have been reported to exist in breast cancer. The aim of the present study was to investigate the clinicopathologic and prognostic significance of the CD44(+)/CD24(-/low) and CD44(-)/CD24(+) tumor phenotypes&amp;amp;amp;amp;amp;#39; prevalence. Double immunohistochemistry was applied on a series of 155 paraffin-embedded breast tissue specimens to detect CD44 and CD24. Evaluation of the phenotypes was performed by image analysis. The prevalence of CD44(+)/CD24(-/low) and CD44(-)/CD24(+) tumor cells was 58.7% and 82.6%, respectively. The dominance of the CD44(+)/CD24(-/low) tumor cells was inversely associated with lymph node metastasis (P = .019) and tended to inversely associate with the stage of the disease (P = .068). Moreover, the prevalence of CD44(+)/CD24(-/low) was found to exert no significant impact on patients&amp;amp;amp;amp;amp;#39; prognosis although it displayed a tendency toward an increase in disease-free survival (P = .074). On the other hand, th...
    Kisspeptins, the products of the KISS1 gene have tumor suppressing and antimetastatic properties. We aimed to study KISS1 and KISS1R expression in colorectal cancer. We analyzed KISS1 and KISS1R expression using immunohistochemistry and... more
    Kisspeptins, the products of the KISS1 gene have tumor suppressing and antimetastatic properties. We aimed to study KISS1 and KISS1R expression in colorectal cancer. We analyzed KISS1 and KISS1R expression using immunohistochemistry and image analysis in normal and malignant tissue samples from 111 patients with colorectal adenocarcinoma. KISS1 expression was much higher in the normal than in the malignant colonic mucosa. Regarding malignant tissues, KISS1 levels were higher in larger tumors, in stage III and IV cancers, in cancers with lymph node metastasis and in tumors located in the distal part of the large intestine. Patients with greater KISS1 levels had worse prognosis. No KISS1R expression was detected in normal or malignant tissues or in liver metastases. KISS1 expression is reduced during the malignant transformation of the colonic mucosa. However, larger and advanced colorectal cancers express more KISS1, without reaching the former normal levels, and increased KISS1 leve...
    Akt is a serine/threonine kinase which is fully activated when phosphorylated (pAkt). The aim of this study was to investigate the expression pattern of phosphorylated Akt at Threonine 308 [pAkt(Thr308)] in association with... more
    Akt is a serine/threonine kinase which is fully activated when phosphorylated (pAkt). The aim of this study was to investigate the expression pattern of phosphorylated Akt at Threonine 308 [pAkt(Thr308)] in association with clinicopathological parameters and various biological markers. Immunohistochemistry was performed on paraffin-embedded tissue specimens from 152 invasive breast carcinomas to detect the expression of the proteins pAkt(Thr308), estrogen (ER) and progesterone (PR) receptors, p53, Ki-67 and c-erbB-2. pAkt(Thr308) protein was immunodetected in the cytoplasm and the nuclei of the malignant cells. pAkt was found to be positively associated with the lobular histological type, while it was found to exert no impact on patients&#39; survival. pAkt(Thr308) immunopositivity was inversely related to Ki-67 and p53 (p=0.013 and p=0.020, respectively), while being positively associated with cerbB2 expression (p=0.005). This is the first study to show a frequent detection of pAkt...
    Cyclooxygenase-2 (COX-2), a critical enzyme in the conversion of arachidonic acid to prostaglandin E2, influences the biological behavior of human tumors, being involved in carcinogenesis, tumor progression, reduced apoptosis and... more
    Cyclooxygenase-2 (COX-2), a critical enzyme in the conversion of arachidonic acid to prostaglandin E2, influences the biological behavior of human tumors, being involved in carcinogenesis, tumor progression, reduced apoptosis and differentiation. The aim of the present study was to investigate the role of COX-2 protein expression in urothelial carcinoma (UC) of the urinary bladder in relation to clinicopathological data and indices of apoptotic potential. Immunohistochemistry was applied to 134 paraffin-embedded specimens of UC for the detection of COX-2, p53, bcl-2, caspase-3, bax protein, MLH1 and hTERT. Ninety-four UCs (70.1%) had an enhanced expression of COX-2. The COX-2 semi-quantitative expression was unrelated to tumor grade and local invasion, but it was positively linked with caspase-3 (CPP32) and bax protein semi-quantitative immunoreactivity (p = 0.007 and p = 0.026), as well as with the quantitative expression of MLH1 (p = 0.019). COX-2 was also found to be inversely co...
    The role of telomere in tumorigenesis is complex. While telomerase activation is suggested to be necessary for tumor growth, it may also help in diminishing genetic instability. The expressions of the telomerase reverse... more
    The role of telomere in tumorigenesis is complex. While telomerase activation is suggested to be necessary for tumor growth, it may also help in diminishing genetic instability. The expressions of the telomerase reverse transcriptase/hTERT and the telomerase associated protein-1/hTEP-1 were investigated in relation to clinicopathological parameters and various proliferative and apoptotic biological markers. The immunohistochemical method ABC/HRP was performed on paraffin sections of 132 patients with urothelial bladder carcinomas to detect the proteins hTERT, hTEP-1, Ki-67, bcl-2, p53 and caspase-3. The hTEP-1 protein was localized in the cytoplasm of cancerous cells (56.6%), while the hTERT protein was detected in the nuclei and the cytoplasm of cancerous cells (57.6% and 45.5%, respectively). hTEP-1 demonstrated an association with lower stage of the disease (p = 0.036), as well as both nuclear and cytoplasmic hTERT (p = 0.018 and p = 0.0001, respectively). Cytoplasmic hTERT showe...
    Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin... more
    Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin embedded tissue specimens from 111 sporadic, invasive breast carcinomas to detect the expression of the proteins BRCA1, ER, PR, erbB2, p53 and Ki67. BRCA1 protein was detected in the nuclei and the cytoplasm of the tumor cells. Nuclear BRCA1 immunoreactivity showed no relation with the classic clinicopathological markers and the expression of cerbB2, p53 and Ki67. Reduced expression of nuclear BRCA1 protein was found to exert an independent favorable impact on both the overall and relapse-free (RF) survival of the patients (p=0.019 and p=0.043, respectively). Cytoplasmic BRCA1 was associated with none of the classic histomorphological indices, except from the lymph node metastasis, with which its relation was found to be inverse (p=0.05), prolonging the RF survival of the patients (p=0.05). Our findings suggest that BRCA1 protein depicts different prognostic significance, according to its subcellular distribution. Nuclear detection of the protein was associated with a worse prognosis, while the cytoplasmic one was related to fewer recurrences as a result of fewer lymph node metastases.
    Aims:  To investigate the clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1‐MMP) and MMP‐9 proteins expression in invasive breast carcinoma and their relationship to tumour proliferation and... more
    Aims:  To investigate the clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1‐MMP) and MMP‐9 proteins expression in invasive breast carcinoma and their relationship to tumour proliferation and expression of c‐erbB2 and peroxisome proliferator‐activated receptor (PPAR) gamma.Methods:  Immunohistochemistry was carried out on 175 paraffin‐embedded breast tissue specimens to detect MT1‐MMP, MMP‐9, oestrogen receptor (ER), progesterone receptor, c‐erbB‐2, Ki67, topoisomerase IIα (topo IIα) and PPARγ protein expression.Results:  Both MT1‐MMP and MMP‐9 were expressed in the cytoplasm of the malignant cells and the peritumoral stroma. Cytoplasmic MT1‐MMP was more often observed in ER+ tumours (P = 0.022), of a lower nuclear grade (P = 0.020) and with reduced expression of Ki67 and topo IIα (P = 0.027 and P = 0.006, respectively). Moreover, cytoplasmic MT1‐MMP was positively associated with MMP‐9 (P = 0.010) and PPARγ (P &lt; 0.0001). Cytoplasmic ...
    Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcriptional factor that regulates the transcription of various target genes. Our purpose is to investigate the clinicopathologic and prognostic... more
    Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcriptional factor that regulates the transcription of various target genes. Our purpose is to investigate the clinicopathologic and prognostic significance of PPARgamma expression in human urothelial bladder cancer (BUC). Immunohistochemistry was applied in 117 paraffin-embedded specimens of human BUC to detect the proteins PPARgamma and Ki67. The image analysis method was used for the evaluation of the immunohistochemical staining. PPARgamma protein was localized in the nuclei of the malignant cells. Its expression was inversely associated with the stage of BUCs (p&amp;lt;0.001), tumor grade (p=0.007) and the expression of the proliferation marker Ki67 (p=0.015) while it was found to exert a favorable effect on patients&amp;#39; overall survival (p=0.001). The findings of the present study suggest that in BUC, PPARgamma expression can identify patients with a better prognosis who suffer from more differentiated, non-invasive tumors, of a low proliferative potential.
    uPA system plays an important role in cancer invasion and metastasis. The binding of uPA to its receptor, uPAR, is necessary for the activation of uPA system. We studied by immunohistochemistry the distribution pattern of uPAR on 173... more
    uPA system plays an important role in cancer invasion and metastasis. The binding of uPA to its receptor, uPAR, is necessary for the activation of uPA system. We studied by immunohistochemistry the distribution pattern of uPAR on 173 paraffin-embedded samples of invasive breast carcinomas in relation to clinicopathologic data and patients&amp;#39; survival. uPAR was detected in both the malignant and stromal cells in the 68.8 and 74.6% of the cases, respectively. uPAR of cancerous cells was more often observed in lobular carcinomas (P=0.012). Stromal expression of uPAR was inversely associated with ER of the tumor (P=0.044) and was found to be an independent prognosticator of patients&amp;#39; shortened relapse-free survival (P=0.018). These results suggest that stromal uPAR influences more directly tumor behaviour, being related to an aggressive tumor phenotype and patients&amp;#39; poor relapse-free survival.
    ObjectiveThe concept that intraarticular crystals of uric acid by themselves trigger episodes of painful gouty arthritis is inconsistent with the clinical reality. Patients with large deposits of monosodium urate monohydrate (MSU)... more
    ObjectiveThe concept that intraarticular crystals of uric acid by themselves trigger episodes of painful gouty arthritis is inconsistent with the clinical reality. Patients with large deposits of monosodium urate monohydrate (MSU) crystals (tophi) do not necessarily experience gouty attacks. In fact, it is the excessive consumption of food or alcohol that elicits the inflammation of the acute gout attack. The aim of this study was to identify the precise mechanism that initiates flares of gouty arthritis.MethodsHuman peripheral blood mononuclear cells (PBMCs) and murine macrophages were stimulated in vitro with MSU, free fatty acids (FFAs), or both in combination. Thereafter, production of interleukin‐1β (IL‐1β) and activation of caspase 1 were determined. Gouty arthritis was induced in mice with deficiencies in the genes for caspase 1, ASC, NALP3, or IL‐1β, and the lack of inflammasome activity during joint swelling or other joint pathologic features was investigated in these mice....
    Kisspeptins, the products of the KISS1 gene, are involved in cancer invasion, migration, metastasis and angiogenesis, while they induce apoptosis in various cancers. Herein, we studied KISS1 expression in colorectal cancer. We analyzed... more
    Kisspeptins, the products of the KISS1 gene, are involved in cancer invasion, migration, metastasis and angiogenesis, while they induce apoptosis in various cancers. Herein, we studied KISS1 expression in colorectal cancer. We analyzed KISS1 expression using immunohistochemistry and image analysis in normal and malignant tissue samples from 60 patients with colorectal adenocarcinoma. The results correlated with various clinicopathological parameters. The expression of KISS1 was much higher in normal than in malignant colonic mucosa. However, among malignant tissues, KISS1 expression was higher in larger tumors (&gt;4 cm) than in smaller ones (≤4 cm) and in stages III and IV than in stages I and II. In addition, it was higher in patients with lymph node metastases. Moreover, KISS1 levels in the normal mucosa and their difference from those in the malignant mucosa were higher in the right part of the large intestine than in the left one. KISS1 expression is reduced during the malignan...
    Mismatch repair (MMR) genes are involved in the recognition and repair of acquired DNA damage, which arises during cell division, thus playing an essential role in preserving genetic stability. Immunohistochemistry was applied to 130... more
    Mismatch repair (MMR) genes are involved in the recognition and repair of acquired DNA damage, which arises during cell division, thus playing an essential role in preserving genetic stability. Immunohistochemistry was applied to 130 specimens from urothelial carcinoma (UC) of the bladder to detect expression of MMR gene products hMSH2 and hMSH6, and to investigate its clinicopathological and prognostic value. hMSH2 and hMSH6 protein expression was exclusively detected in the nuclei of malignant cells. Of the 112 cases evaluable for hMSH2, 29 (25.9%) were negative and of the 130 UCs evaluable for hMSH6, 64 (49.2%) were negative, and were thus considered to depict MSI. Nuclear hMSH2 values were statistically lower in non‐invasive UCs (Ta‐T1) (p=0.013) and in carcinomas with decreased p53 staining (p=0.04). Lower hMSH6 values were more often met in well‐differentiated tumors (p&lt;0.0001) and in tumors with low expression of p53 (p=0.016), topoIIα and caspase 3 (p=0.017 and p=0.018, r...
    INTRODUCTION The aim of the present study was to investigate the distribution of both lymphatics and blood microvessels in invasive breast carcinomas and the clinicopathological and prognostic significance of their density and size... more
    INTRODUCTION The aim of the present study was to investigate the distribution of both lymphatics and blood microvessels in invasive breast carcinomas and the clinicopathological and prognostic significance of their density and size related parameters as well as their correlation with the proliferative potential of the tumor and VEGF-C and -D expression. METHODS Both single and double immunohistochemistry were applied on a series of 146 paraffin-embedded breast tissue specimens to detect VEGF-C and -D as well as lymphatics and blood microvessels, respectively. Computer-assisted morphometry was performed to evaluate the blood and lymphatic vessel density (BVD and LVD respectively) as well as various vascular size related parameters. RESULTS Lymphatics were detected within the stroma at the tumor border, while blood vessels were located in both the interior of the tumor mass and peritumor stroma. BV major axis, minor axis and perimeter inversely correlated with ER (p=0.011, p=0.023 and...
    Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The purpose of the present study was to investigate the involvement of COX-2 protein in breast cancer biological... more
    Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The purpose of the present study was to investigate the involvement of COX-2 protein in breast cancer biological behavior through its correlation with the well-known clinicopathological parameters and the expression of p53, c-erbB-2, topoisomerase IIalpha (topoIIalpha) and peroxisome proliferator-activated receptor (PPARgamma) proteins, as well as its effect on patients&amp;#39; survival. We performed immunohistochemistry to detect COX-2, estrogen receptor (ER), progesterone receptor (PR), p53, c-erbB-2, topoIIalpha and PPARgamma proteins in 175 cases of invasive breast carcinomas. The results were elaborated by statistic analysis. Cytoplasmic expression of COX-2 was detected in 66.9% of breast carcinoma samples and was inversely correlated with both nuclear and histological grade (p &amp;lt; 0.0001 and p = 0.039, respectively), whereas its association with PR was found to be positive (p = 0.016). COX-2 expression was inversely correlated with topoIIalpha and p53 (p = 0.033 and p = 0.002, respectively), whereas its association with PPARgamma was parallel (p &amp;lt; 0.0001). In addition, c-erbB-2 of tumor cells was inversely correlated with COX-2 in stromal cells of the tumor (p = 0.011). Neither univariate nor multivariate analysis demonstrated any association between COX-2 expression and patient overall or disease-free survival. The current data suggest that increased expression of COX-2 may be related to breast carcinomas with less aggressive phenotype. This suggestion is further supported by the positive correlation between COX-2 and PPARgamma, since the latter is considered to be indicative of a less malignant phenotype of tumor cells.
    To investigate the clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 proteins expression in invasive breast carcinoma and their relationship to tumour proliferation and... more
    To investigate the clinicopathological and prognostic significance of membrane type 1 matrix metalloproteinase (MT1-MMP) and MMP-9 proteins expression in invasive breast carcinoma and their relationship to tumour proliferation and expression of c-erbB2 and peroxisome proliferator-activated receptor (PPAR) gamma. Immunohistochemistry was carried out on 175 paraffin-embedded breast tissue specimens to detect MT1-MMP, MMP-9, oestrogen receptor (ER), progesterone receptor, c-erbB-2, Ki67, topoisomerase IIalpha (topo IIalpha) and PPARgamma protein expression. Both MT1-MMP and MMP-9 were expressed in the cytoplasm of the malignant cells and the peritumoral stroma. Cytoplasmic MT1-MMP was more often observed in ER+ tumours (P = 0.022), of a lower nuclear grade (P = 0.020) and with reduced expression of Ki67 and topo IIalpha (P = 0.027 and P = 0.006, respectively). Moreover, cytoplasmic MT1-MMP was positively associated with MMP-9 (P = 0.010) and PPARgamma (P &amp;lt; 0.0001). Cytoplasmic MMP-9 was inversely associated with Ki67 (P = 0.034) and topo IIalpha (P = 0.004), whereas its relationship with MT1-MMP (P = 0.034) and PPARgamma (P = 0.024) was found to be positive. Stromal MMP-9 was more often observed in c-erbB2+ tumours (P = 0.043) and had an unfavourable impact on overall and relapse-free survival in both univariate (P = 0.0157 and P = 0.0274, respectively) and multivariate analyses (P = 0.007 and P = 0.024, respectively). Cytoplasmic MT1-MMP and MMP-9 seem to be related to well-differentiated tumours, with a low proliferation potential, while stromal MMP-9 is associated with an aggressive tumour phenotype and is recognized as an independent poor prognostic indicator.
    The objective of this study is to systematically review the epidemiology and the clinical and viro- logic aspects of multicentric Castleman&#39;s disease in HIV-positive patients and to evaluate treatment strategies and outcome,... more
    The objective of this study is to systematically review the epidemiology and the clinical and viro- logic aspects of multicentric Castleman&#39;s disease in HIV-positive patients and to evaluate treatment strategies and outcome, especially in relation to HAART administration. The authors have conducted a systematic review of the English literature for all cases of newly diagnosed multicentric Castleman&#39;s disease in HIV-positive
    Kisspeptins, the products of the KISS1 gene have tumor suppressing and antimetastatic properties. We aimed to study KISS1 and KISS1R expression in colorectal cancer. We analyzed KISS1 and KISS1R expression using immunohistochemistry and... more
    Kisspeptins, the products of the KISS1 gene have tumor suppressing and antimetastatic properties. We aimed to study KISS1 and KISS1R expression in colorectal cancer. We analyzed KISS1 and KISS1R expression using immunohistochemistry and image analysis in normal and malignant tissue samples from 111 patients with colorectal adenocarcinoma. KISS1 expression was much higher in the normal than in the malignant colonic mucosa. Regarding malignant tissues, KISS1 levels were higher in larger tumors, in stage III and IV cancers, in cancers with lymph node metastasis and in tumors located in the distal part of the large intestine. Patients with greater KISS1 levels had worse prognosis. No KISS1R expression was detected in normal or malignant tissues or in liver metastases. KISS1 expression is reduced during the malignant transformation of the colonic mucosa. However, larger and advanced colorectal cancers express more KISS1, without reaching the former normal levels, and increased KISS1 levels are associated with worse prognosis. Finally, neither the normal nor the malignant colonic epithelial cells produce KISS1R.
    Cells with distinct phenotypes and stem cell-like properties have been reported to exist in breast cancer. The aim of the present study was to investigate the clinicopathologic and prognostic significance of the CD44(+)/CD24(-/low) and... more
    Cells with distinct phenotypes and stem cell-like properties have been reported to exist in breast cancer. The aim of the present study was to investigate the clinicopathologic and prognostic significance of the CD44(+)/CD24(-/low) and CD44(-)/CD24(+) tumor phenotypes&#39; prevalence. Double immunohistochemistry was applied on a series of 155 paraffin-embedded breast tissue specimens to detect CD44 and CD24. Evaluation of the phenotypes was performed by image analysis. The prevalence of CD44(+)/CD24(-/low) and CD44(-)/CD24(+) tumor cells was 58.7% and 82.6%, respectively. The dominance of the CD44(+)/CD24(-/low) tumor cells was inversely associated with lymph node metastasis (P = .019) and tended to inversely associate with the stage of the disease (P = .068). Moreover, the prevalence of CD44(+)/CD24(-/low) was found to exert no significant impact on patients&#39; prognosis although it displayed a tendency toward an increase in disease-free survival (P = .074). On the other hand, th...
    Vascular endothelial growth factor-C (VEGF-C) has been associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis and was reported to have an anti-apoptotic and proliferative role. An immunohistochemical study was... more
    Vascular endothelial growth factor-C (VEGF-C) has been associated with angiogenesis, lymphangiogenesis and regional lymph node metastasis and was reported to have an anti-apoptotic and proliferative role. An immunohistochemical study was applied to 123 specimens of bladder urothelial carcinoma (BUC) to detect VEGF-C and investigate its clinicopathological and prognostic value. VEGF-C-immunostained BUC specimens (123) were statistically correlated with histological grade and stage, patient overall survival and immuno-expression of Ki-67 and bax proteins. VEGF-C immunopositivity (27/123 BUCs, 22.0%) was inversely correlated with tumor stage and bax immunoexpression (p = 0.007 and p = 0.032, respectively). VEGF-C-positive BUCs tended to have better prognosis (univariate analysis). VEGF-C might be associated with an anti-apoptotic phenotype. Our controversial results regarding patient survival suggest that the role of VEGF-C in BUC progression and prognosis remains to be clarified.
    Our aim was to study the expression pattern of tissue inhibitor of metalloproteinases (TIMP)-3 protein in invasive breast carcinoma, and its clinicopathological and prognostic value as well as its relation to markers indicative of the... more
    Our aim was to study the expression pattern of tissue inhibitor of metalloproteinases (TIMP)-3 protein in invasive breast carcinoma, and its clinicopathological and prognostic value as well as its relation to markers indicative of the tumor phenotype. Immunohistochemistry was performed on paraffin-embedded tissue specimens from 173 invasive breast carcinomas to detect the proteins TIMP-3, estrogen receptor (ER), progesterone receptor, p53, c-erbB-2, topoisomerase IIalpha and Bcl-2. TIMP-3 protein was immunodetected in the cytoplasm of the malignant cells and the peritumoral stroma, as well as in in situ carcinoma and normal epithelium. Reduced expression of TIMP-3 protein within cancer cells was correlated with carcinomas of high nuclear and histological grade (p = 0.032 and p = 0.015, respectively), and low ER expression (p = 0.053). Moreover, TIMP-3 immunopositivity was inversely correlated with the expression of p53 and topoIIalpha proteins (p = 0.002 and p = 0.008, respectively)...
    ... 2.4. Statistical analysis. Correlations were assessed using the Spearman rank correlationtest for 2 continuous variables and the Mann-Whitney U test and Kruskall-Wallis test when one variable was continuous and the other categorical.... more
    ... 2.4. Statistical analysis. Correlations were assessed using the Spearman rank correlationtest for 2 continuous variables and the Mann-Whitney U test and Kruskall-Wallis test when one variable was continuous and the other categorical. ...
    ... a Service de médecine interne, 5, hôpital Evangelismo, 45–47, Hipsilantou street, Kolonaki, 10676 Athènes, Grèce. b Service de radiologie, hôpital Evangelismo, 45–47, Hipsilantou street, Kolonaki, 10676 Athènes, Grèce. Accepted 16 May... more
    ... a Service de médecine interne, 5, hôpital Evangelismo, 45–47, Hipsilantou street, Kolonaki, 10676 Athènes, Grèce. b Service de radiologie, hôpital Evangelismo, 45–47, Hipsilantou street, Kolonaki, 10676 Athènes, Grèce. Accepted 16 May 2007. Available online 2 April 2008. ...
    β-Catenin has a crucial role in cell–cell adhesion as well as a signaling role as a member of the Wnt pathway. The aim of this study was to examine the clinicopathological and prognostic value of phosphorylated β-catenin, as well as its... more
    β-Catenin has a crucial role in cell–cell adhesion as well as a signaling role as a member of the Wnt pathway. The aim of this study was to examine the clinicopathological and prognostic value of phosphorylated β-catenin, as well as its relation to the tumors’ phenotype, in breast cancer. Immunohistochemistry was applied on 141 paraffin-embedded breast tissue specimens for the
    Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The purpose of the present study was to investigate the involvement of COX-2 protein in breast cancer biological... more
    Cyclooxygenase (COX) is the rate-limiting enzyme that catalyzes the conversion of arachidonic acid to prostaglandins. The purpose of the present study was to investigate the involvement of COX-2 protein in breast cancer biological behavior through its correlation with the well-known clinicopathological parameters and the expression of p53, c-erbB-2, topoisomerase IIalpha (topoIIalpha) and peroxisome proliferator-activated receptor (PPARgamma) proteins, as well as its effect on patients&amp;#39; survival. We performed immunohistochemistry to detect COX-2, estrogen receptor (ER), progesterone receptor (PR), p53, c-erbB-2, topoIIalpha and PPARgamma proteins in 175 cases of invasive breast carcinomas. The results were elaborated by statistic analysis. Cytoplasmic expression of COX-2 was detected in 66.9% of breast carcinoma samples and was inversely correlated with both nuclear and histological grade (p &amp;lt; 0.0001 and p = 0.039, respectively), whereas its association with PR was found to be positive (p = 0.016). COX-2 expression was inversely correlated with topoIIalpha and p53 (p = 0.033 and p = 0.002, respectively), whereas its association with PPARgamma was parallel (p &amp;lt; 0.0001). In addition, c-erbB-2 of tumor cells was inversely correlated with COX-2 in stromal cells of the tumor (p = 0.011). Neither univariate nor multivariate analysis demonstrated any association between COX-2 expression and patient overall or disease-free survival. The current data suggest that increased expression of COX-2 may be related to breast carcinomas with less aggressive phenotype. This suggestion is further supported by the positive correlation between COX-2 and PPARgamma, since the latter is considered to be indicative of a less malignant phenotype of tumor cells.

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