Mirsad Doric
University of Sarajevo, Medicinski fakultet, Department Member
Aim To investigate the impact of pre-treatment serum total prostate-specific antigen (PSA) level on prevalence of prostate carcinoma detection in prostate core needle biopsy, and its correlation with established prognostic factors.... more
Aim To investigate the impact of pre-treatment serum total prostate-specific antigen (PSA) level on prevalence of prostate carcinoma detection in prostate core needle biopsy, and its correlation with established prognostic factors. Methods Prostate needle biopsy samples of 115 patients with available pre-treatment serum total PSA (tPSA) level were analysed. For all cases where morphology alone was insufficient, immunohistochemistry was performed using p63, CKHMW and AMACR antibody panel in order to confirm or exclude the existence of prostate carcinoma. Results Statistically significant positive correlation between serum total PSA values and prevalence of finding prostate carcinoma in needle biopsy specimens was found (p=0.011), as well as in the case when the patients were classified into groups according to tPSA levels (p=0.028). Serum total PSA values and levels (level groups) showed significant positive correlation with Gleason score (p=0.029 and p=0.036, respectively) and Grade Group of prostate carcinomas (p=0.044 and p=0.046, respectively). Sensitivity of the screening test by using 4 ng/mL as cut off value for tPSA was 94.12% (CI: 80.32-99.28%), specificity 8.64% (CI: 3.55-17.00%), positive predictive value 30.19% (CI: 21.65-39.87%) and negative predictive value 77.78% (CI: 39.99-97.19%). Conclusion The increase of serum tPSA value increases the likelihood of finding prostate cancer on needle biopsy specimens. Due to such findings and its positive correlation with a grade of prostate cancer, our study indicates that tPSA can still be considered as a useful tool both in detecting and predicting aggressiveness of prostate cancer.
Research Interests:
Introduction: Tumor-associated macrophages (TAM) are the most common inflammatory cells in the tumor microenvironment (TM). As a response to microenvironmental signals, they polarize into tumor resisting M1 or promoting M2 macrophages.... more
Introduction: Tumor-associated macrophages (TAM) are the most common inflammatory cells in the tumor microenvironment (TM). As a response to microenvironmental signals, they polarize into tumor resisting M1 or promoting M2 macrophages. TAM and tumor-associated dendritic cells (TADC) can either promote tumor growth and tissue invasiveness or have anti-tumor activity. The aim of the study was the examination of prognostic value in the individual cell population in TM and their correlation with clinicopathological parameters of gastric cancer. Materials and Methods: The study analyzed 60 samples of gastric cancer, known status of regional lymph nodes and without dissemination at the time of diagnosis. The control group was normal gastric tissue samples. Traditional parameters of biological aggressiveness, tumor size, histological grade, and lymphovascular invasion, are determined after standard hematoxylin-eosin staining. TAM and TADS have been evaluated using the immunohistochemical method with CD68 (TAM), TNFa (TAM-M1), CD163 (TAM-M2), and S100 (TADC) antibodies. Expression evaluation of the tissue antigen was carried out by semiquantitative methods. Results: There were statistically significant differences of TAM density (P 0.05). Conclusion: TAMs and TADC have shown potential as biomarkers for evaluating the gastric cancer staging and progression. They showed promising prediction in depth of invasion, histological grade of tumor and tumor size. Keywords: gastric cancer, tumor microenvironment, TAM, TAM-M1/M2, TADC
Research Interests:
Objective: To investigate a possible association between peritumoral lymphatic vessel density (LVD) and adipose tissue invasion (ATI) of cancer cells at the tumor margin and their correlation with other prognostic parameters in breast... more
Objective: To investigate a possible association between peritumoral lymphatic vessel density (LVD) and adipose tissue invasion (ATI) of cancer cells at the tumor margin and their correlation with other prognostic parameters in breast cancer, including lymph node status. Material and methods: Data of 75 patients with breast carcinoma were evaluated through combination of peritumoral LVD and ATI at the tumor margin and compared with clinicopathological parameters. Peritumoral LVD was assessed by immunostaining for D2-40 using the Chalkley counting method. Marginal ATI was defined as either the presence of more than 20 cancer cells in direct contact with the adipose tissue or as the presence of cancer cells in the adipose tissue. Cases were evaluated concerning to patient’s age, tumor size using the TNM staging system, histological type, histological grade (Nottingham histological score, Elston and Ellis), lymphovascular invasion, lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR), HER2/neu status and Ki-67. Results: The relationship was identified between LVD and marginal ATI but without statistical significancy (r = -0,207; p=0,113). There was a significant correlation of the marginal ATI with Ki-67 expression (r=0,250; p =0.03). The regression model (all variables according to ATI) showed a significant total effect (p <0.05), where Ki-67 was an only independent indicator of ATI. Conclusion: The present study suggests that adipose tissue invasion of cancer cells at the tumor margin can be a better predictive biologic indicator of aggressiveness than peritumoral lymphatic vessel density in breast carcinoma. Keywords: breast carcinoma, peritumoral lymphatic vessel density, marginal adipose tissue invasion.
Research Interests:
Ankylosing spondylitis is a serious ailment that affects people, and the first signs or symptoms usually occurr between the ages of 15 and 45. While the condition is mostly prevalent in men, women are not immune to this disease. This... more
Ankylosing spondylitis is a serious ailment that affects people, and the first signs or symptoms usually occurr between the ages of 15 and 45. While the condition is mostly prevalent in men, women are not immune to this disease. This problem is diagnosed with a combination of clinical history and X-rays, pathology and HLAB27 test. The aim of this case study is to demonstrate how macroscopic and microscopic analysis can be used for identification of the disease from a forensic point of view. In April 2018, we exhumed 11 remains near the city Višegrad, twenty-five years after the last war. All the remains were completely skeletonized. The skeleton of a female was specific and shaped like a bamboo branch, with a partial knitting of vertebral bodies in the lumbar region of spine and with total knitting in the thoracic part. The spinous processes were completely knitted. Her son gave informations for verbal autopsy that she had trouble walking and doing normal activities during life. Sam...
Research Interests:
Objectives : The main objective of the study was to determine whether the distribution fsaand th Gastric cancer progression in correlation with distribution and density of T-lymphocytes e level of fsa: The main objective of the study was... more
Objectives : The main objective of the study was to determine whether the distribution fsaand th Gastric cancer progression in correlation with distribution and density of T-lymphocytes e level of fsa: The main objective of the study was to determine whether the distribution and the level of density of tumor infiltrating CD4+ and CD8+ T-lymphocytes correlates with standard prognostic factors for gastric cancer and whether it has impact on tumor progression. Methods: The study included 60 tissue samples of operable gastric carcinomas of known regional lymph node status, stained by standard hematoxylin eosin and immunohi Objectives: The main objective of the study was to determine whether the distribution and the level of density of tumor infiltrating CD4+ and CD8+ T-lymphocytes correlates with standard prognostic factors for gastric cancer and whether it has impact on tumor progression. Methods: The study included 60 tissue samples of operable gastric carcinomas of known regional lym...
Research Interests:
Introduction: Tumor microenvironment plays a significant role in tumor progression. Tumor stroma is one of the strongest modifiers of tumor cell response, cancer behavior, and cancer progression. This study aimed to investigate the... more
Introduction: Tumor microenvironment plays a significant role in tumor progression. Tumor stroma is one of the strongest modifiers of tumor cell response, cancer behavior, and cancer progression. This study aimed to investigate the correlation of matrix metalloproteinase-9 (MMP-9) expression and tumor-stroma ratio (TSR) with standard clinicopathological parameters in different molecular subtypes of breast cancer.Methods: Ninety biopsy samples of primary breast cancer diagnosed at the Department of Pathology, School of Medicine, Sarajevo, were selected for this study. The molecular subtype was determined based on the immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67. Stromal and tumoral MMP-9 immunohistochemical expression and the TSR were determined for each tumor.Results: Tumoral MMP-9 expression correlated positively with the presence of lymphovascular invasion (p= 0.016). TSR showed significant associat...
Research Interests:
Aim To evaluate the relationship between numerical and categorical immunohistochemical score of Ki-67 and human epidermal growth factor of receptor 2 (HER2) with clinicopathological parameters of breast cancer (BC). Methods The study... more
Aim To evaluate the relationship between numerical and categorical immunohistochemical score of Ki-67 and human epidermal growth factor of receptor 2 (HER2) with clinicopathological parameters of breast cancer (BC). Methods The study included 311 patients with invasive BC diagnosed at the Department of Pathology, School of Medicine in Sarajevo, Bosnia and Herzegovina, during the period 2015-2019. The expression level of Ki-67 and HER2 was detected by immunohistochemical analysis. Results The expression of Ki-67, as a numerical variable correlated significantly with tumour grade (p=0.025), progesterone receptor (PR) (p=0.034) and categorical score of HER2 (p=0.028). When Ki-67 was categorized into high (>14%) and low (≤14%) level groups, a statistically significant association was found between Ki-67 level groups and HER2 status (categorical and numerical) (p=0.001 and p=0.043, respectively), as well as significant negative linear correlation with PR (p=0.037). The expression of H...
Research Interests:
Background: Bone morphogenetic protein -4 (BMP-4) plays important role in many aspects of carcinogenesis but is also involved in progression and metastasis of breast cancer where its precise role is yet to be elucidated. Objective: Since... more
Background: Bone morphogenetic protein -4 (BMP-4) plays important role in many aspects of carcinogenesis but is also involved in progression and metastasis of breast cancer where its precise role is yet to be elucidated. Objective: Since the majority of studies related to BMP-4 expression in breast cancer were conducted on cell lines of mouse models, we aimed to investigate BMP-4 tissue expression in primary human breast cancer and to correlate it with standard pathological factors for breast cancer, progression and survival. Methods: We analyzed immunohistochemical expression of BMP-4 in primary breast cancer tissue of 97 patients, correlated it with standard pathological factors for breast cancer and investigated its impact on progression and survival. Results: BMP-4 expression was positive in 74.23% breast cancer tissue specimens. We found that hormone positive breast tumors are more likely to show BMP-4 strong granular staining pattern (p<0.01; p=0.029, respectively). There w...
Research Interests:
Interdigitating dendritic cell sarcoma is extremely rare neoplasm that mainly occurs in the lymph nodes. Only 45 cases have been reported in the literature to date. We report a case of this sarcoma arising from the liver and lung, a... more
Interdigitating dendritic cell sarcoma is extremely rare neoplasm that mainly occurs in the lymph nodes. Only 45 cases have been reported in the literature to date. We report a case of this sarcoma arising from the liver and lung, a previosly unreported site for this neoplasm. An 19-year-old girl deteriorated rapidly after artificial abortion and died 4 weeks later. Autopsy showed markedly enlarged liver and lung with numerous nodules up to 0.5 centimeters in diameter. Microscopically, nodules was composed of large pleomorphic cells that were immunohistochemically positive for proteins S-100 and vimentin, some of them expressed positivity to fascin and CD 68, with a rich small CD3 positive T lymphocytic infiltrateite around them. Based of these findings, the present case was diagnosed as interdigitating dendritic cell sarcoma, a neoplasm that remains a diagnostic and clinical challenge, because it can mimic a wide variety of other malignant tumors and tumor-like lesions.
Research Interests:
Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a natural inhibitor of matrix metalloproteinases (MMPs). Aim of this study was to assess the immunohistochemical expression of TIMP-1 in invasive breast carcinomas, and to examine its... more
Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a natural inhibitor of matrix metalloproteinases (MMPs). Aim of this study was to assess the immunohistochemical expression of TIMP-1 in invasive breast carcinomas, and to examine its association with classical clinico-pathological parameters, oestrogen receptor, progesterone receptor and Her-2/neu protein expression. Immunohistochemistry was used to determine the expression of TIMP-1 on 38 paraffin-embedded breast tissue specimens - 18 with invasive ductal carcinoma, 10 with invasive lobular carcinoma, and 10 specimens from patients with fibrocystic breast disease. TIMP-1 protein was immunodetected in the carcinoma cells, fibroblasts and inflammatory cells of the stroma in 92,9%, 65,8%, and 65,8% of cases, respectively. TIMP-1 protein expression in carcinoma cells showed positive correlation with TIMP-1 protein expression in peritumoural fibroblasts (p=0,010). Positive peritumoural fibroblast TIMP-1 expression was associated with ...
Research Interests: Immunohistochemistry, Medicine, Humans, Female, Aged, and 4 moreMiddle Aged, Adult, Cytoplasm, and Breast Neoplasms
Giant cell fibroblastoma (GCF) is a rare type of fibroblastic tumor, first described as a juvenile form of dermatofibrosarcoma. Although recurrences are common after local surgical resection, metastasis is not reported.We report a case of... more
Giant cell fibroblastoma (GCF) is a rare type of fibroblastic tumor, first described as a juvenile form of dermatofibrosarcoma. Although recurrences are common after local surgical resection, metastasis is not reported.We report a case of a 4-year-old boy with giant cell fibroblastoma, in which the neoplasm was characterized histologically by a proliferation of spindle-shaped cells intermixed with pseudovascular channels called "angiectold spaces". The spaces were lined by large cells with pleomorphic nuclei intermixed with multinucleated cells. Immunohistochemically, the tumor stained diffusely for vimentin and CD34, but negative for S 100 protein. Since the initial description in 1982, less than 100 cases of GCF have been reported. This patient's presentation is particularly interesting because present the first case reported in Bosnia and Herzegovina.
Research Interests:
AIM OF THE STUDY To investigate the correlation between the expression of HER-2 membrane protein and basic pathohistological parameters in cases of infiltrative breast cancer. MATERIAL AND METHODS Sixty-nine cases of lobular infiltrative... more
AIM OF THE STUDY To investigate the correlation between the expression of HER-2 membrane protein and basic pathohistological parameters in cases of infiltrative breast cancer. MATERIAL AND METHODS Sixty-nine cases of lobular infiltrative breast cancer were investigated. Mastectomy with a dissection of axillary's lymph nodes was performed in all cases. Upon standard procedure of formalin fixation, embedding in paraffin and examination of slides stained with hematoxillin-eosin, a semiquantitaive method of evaluation of immunohistochemical expression of the HER-2 protein has been performed in all tissue samples of the tumor. RESULTS Majority of patients (91,3 %) were above 41 year-of-age. In the majority of cases (44,9 %) cancer's diameter ranged from 20-50 mm (pT2), with a moderate degree of differentiation (46,4 %), no signs of vascular invasion (50,7 %) and no metastases in axillary's lymph nodes (65,2 %). Evaluation of immunohistochemical expression of the HER-2 protein...
Research Interests:
Introduction: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the progression of several tumors, including breast cancer. Our aim was to investigate the association of... more
Introduction: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the progression of several tumors, including breast cancer. Our aim was to investigate the association of immunohistochemical expression of protein MMP-2, and -9 and tissue inhibitors TIMP-1,-2,-3 by tumoral cells in the process of angiogenesis and to define their relation with clinicopathological features for breast cancer. Methods: Immunohistochemical analysis of MMP-2,-9, TIMP-1,-2,-3, endoglin/CD105, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status was performed on 79 tissue samples of breast cancer with axillary lymph node dissection. Results: Statistically significant difference was found between mean age of patients and tissue inhibitors of metalloproteinase (TIMP-1) expression status (p=0.008), i.e., women with TIMP-1 negative tumors were on average younger (mean age 46.5) compared to women with TIMP-...
Research Interests:
In the early stages of cutaneous malignant melanoma (MM), it is extremely difficult to predict adequately the risk from hematogenic and lymphatic metastasis. We investigate whether the immunohistochemical expression of Ki-67 and estrogen... more
In the early stages of cutaneous malignant melanoma (MM), it is extremely difficult to predict adequately the risk from hematogenic and lymphatic metastasis. We investigate whether the immunohistochemical expression of Ki-67 and estrogen receptor beta (ERβ) in cells of MM could predict the status of regional lymph nodes. A total of 55 tissue samples of primary cutaneous melanomas with known status of regional lymph nodes were retrospectively evaluated for Ki-67 and ERβ expression by quantitative immunohistochemistry and then correlated with the status of regional lymph nodes and relevant clinicopathologic parameters. The ERβ-positive expression was detected in 38 of 55 tumors (69.09%). The Clark level showed a strong correlation with ERβ expression, as well as pT stage. All cases of MM showed Ki-67-positive expression and an elevated Ki-67 expression was strongly associated with increased Breslow thickness, Clark level, ulceration, lymphovascular invasion, number of mitosis, and pT stage. Logistic regression analysis showed that when ERβ levels increase by 1%, the risk of positive lymph nodes decreases by 7% (odds ratio=0.930; 95% confidence interval, 0.87-0.99; P=0.036), and, when the Ki-67 expression increases by 1%, the risk of lymph nodes&amp;amp;#39; positivity increases by 10% (odds ratio=1.108; 95% confidence interval, 1.02-1.19; P=0.009). Correlation between expression of Ki-67 and ERβ and the status of lymph nodes has better prognostic significance than the relationship between melanoma thickness and the status of lymph nodes. Our study showed a significant prognostic value of Ki-67 expression in predicting the behavior of MM and the potential prognostic significance of ERβ.
Research Interests:
The primary malignant melanoma of the ovary is a rare kind of neoplasm. This one is in the world literature the eleventh well-documented case having developed in the ovary of a 66-year-old woman. A unilateral ovarian teratoma was removed,... more
The primary malignant melanoma of the ovary is a rare kind of neoplasm. This one is in the world literature the eleventh well-documented case having developed in the ovary of a 66-year-old woman. A unilateral ovarian teratoma was removed, within which a malignant melanoma was found. The junctional activity of melanocytes was demonstrated in the epidermis within the teratoma. An extraovarian primary melanoma was not observed. The patient was treated with a bilateral adnexectomy and hysterectomy.
Research Interests:
SUMMARY Telepathology today has a great importance in a world of telemedicine. Data transfer from medical centers to distant location is of a great value so the word “telemedicine” itself means “medicine over distance”. The basic aim of... more
SUMMARY Telepathology today has a great importance in a world of telemedicine. Data transfer from medical centers to distant location is of a great value so the word “telemedicine” itself means “medicine over distance”. The basic aim of use of telepathology is establishing a direct communication between small centers and referral centers in the country as well as establishing connections with referral center abroad for diagnostic, consultation and educational purposes. Transmission of images may be of still images or video (either recorded of sent as a live feed from a video camera attached to a microscope). The image to be transmitted my be selected by the person sending the image or, if suitable equipment is available, the distant person reciving the images may have remote control of a microscope stage, objectives and focusing. Bosnian experiences have been presented together with experiences abroad and its benefits. Telemedicine in Bosnia and Herzegovina is in process of developm...
Breast cancer is a heterogeneous disease that includes several molecular types, characterized by the expression profile of sex hormone receptors, HER2 protein, cytokeratin 5, p53, and Bcl-2. EGFR is an additional marker predominantly... more
Breast cancer is a heterogeneous disease that includes several molecular types, characterized by the expression profile of sex hormone receptors, HER2 protein, cytokeratin 5, p53, and Bcl-2. EGFR is an additional marker predominantly expressed by basal-like carcinoma, but its significance in the other types is not completely understood. The aim of this study was to analyze the immunohistochemical expression of EGFR and its relationships with other factors of prognosis. There were investigated benign lesions and 84 cases with invasive breast carcinoma that were submitted first to the molecular classification. Next, we performed the staining for EGFR and two patterns of the final product of reaction were described. EGFR expression was found in 41.66% of the cases with basal-like carcinoma, in 50% of the cases with luminal B carcinoma, and in 21.42% of the cases with HER2 overexpression. A significant correlation was found between EGFR expression and degree of differentiation and dista...
Research Interests:
The aim of this study was to investigate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2 proteins in 14 cases of non-small cell lung cancer and to establish their correlation to classical clinico-pathological findings, and alleged... more
The aim of this study was to investigate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2 proteins in 14 cases of non-small cell lung cancer and to establish their correlation to classical clinico-pathological findings, and alleged prognostic value to estimate biological potential of tumor. Retrospective pilot study of the surgically treated non-small cell lung cancer biopsy specimen, paraffin embedded, used immunohistochemical method to demonstrate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2. Protein quantification was performed by the semi-quantitative method. Achieved results were correlated with classical clinico-pathological parameters, like tumor size, histological type, differentiation level, presence of vascular invasion and metastasis in regional lymph nodes. Out of 14 cases of non-small cell lung cancer, squamous cell carcinoma was found in 7 patients, giant cell carcinoma in 3, adenocarcinoma in 2, and 1 case of pleomorphic and mucoepidermoid carcinoma. Expre...
Research Interests:
The main active component of preparation HEPALIP FORTE is EPL--essential phospholipids. Their chemical structure corresponds to that of endogen phospholipids, but they have functional superiority because of the content of unsaturated... more
The main active component of preparation HEPALIP FORTE is EPL--essential phospholipids. Their chemical structure corresponds to that of endogen phospholipids, but they have functional superiority because of the content of unsaturated fatty acids. Essential phospholipids in combination with the vitamins have been used in the treatment of liver diseases, dyslipoproteinaemias and intoxications with consequent liver failure. Acute toxicity study on HEPALIP FORTE was performed on Wistar rats. The main aim of toxicology studies for the drug registration process is evaluation of the toxic potential and risks of human exposition to the substance (Gelbke et al., 1999). Acute toxicity is an orientation point of the test substance toxicity and represents a starting test for the toxicological evaluation. Study included one oral dose of the substance, applied with oesophageal intubations. There were three dose-levels: 300, 500 and 1000 mg/kg. No lethality was recorded and statistical analysis of...
A case of the acute haemorrhaging ulcus in a three-months old infant with lethal outcome is presented in this paper. The unclear proximal gastrointestinal haemorrhage didn't indicate the possibility of the presence of ulcer, due to... more
A case of the acute haemorrhaging ulcus in a three-months old infant with lethal outcome is presented in this paper. The unclear proximal gastrointestinal haemorrhage didn't indicate the possibility of the presence of ulcer, due to the absence of frequent etiologic factors of the inception at this age.
Research Interests:
Introduction: The lymphatic vasculature is an important route for the metastatic spread of human cancer. However, the extent to which this depends on lymphangiogenesis or on invasion of existing lymph vessels remains controversial. The... more
Introduction: The lymphatic vasculature is an important route for the metastatic spread of human cancer. However, the extent to which this depends on lymphangiogenesis or on invasion of existing lymph vessels remains controversial. The goal of this study was to investigate the existence of lymphangiogenesis in invasive breast carcinoma: by measuring the lymphatic vessels density (LVD) and lymphatic endothelial cell proliferation (LECP) and their correlation with various prognostic parameters in breast cancer, including lymphovascular invasion (LVI). Methods: Lymphatic vessels density was investigated in 75 specimens of invasive breast carcinoma by immunostaining for D2-40 using the Chalkley counting method. Endothelial proliferation in lymphatic vessels was analyzed by dual-color immunohistochemistry with D2-40 and Ki-67. Results: Decrease of intra and peritumoral LVD in invasive breast carcinoma compared to fibrocystic breast disease was detected (p=0.002). Lymphatic endothelial cell proliferation was significantly higher in invasive breast cancer (p=0.008) than in the fibrocystic breast disease. LECP showed a correlation with histological grade of the tumor (p=0.05). Involvement of axillary lymph nodes with metastatic tissue was in strong correlation only with existence of lymphatic vascular invasion (p=0.0001). Conclusion: These results suggest that development of breast cancer promotes proliferation of lymphatic endothelial cells whose level correlates with histological grade of tumor, but in a scope that is insufficient to follow growth of tumor tissue that invades them and destruct them. This might explain the decrease of lymphatic vessels density.