ABSTRACTPeriodontal disease is a bacterially mediated chronic inflammatory disease that results in destruction of the periodontal ligament (PDL) and alveolar bone that surround and support the dentition. While their precise roles are not... more
ABSTRACTPeriodontal disease is a bacterially mediated chronic inflammatory disease that results in destruction of the periodontal ligament (PDL) and alveolar bone that surround and support the dentition. While their precise roles are not well understood, periodontal pathogens, includingTreponema denticola, are believed to initiate the destructive inflammatory responses and dysregulation of tissue homeostasis that characterize the disease. These responses are believed to result from both proinflammatory effects of acylated bacterial membrane components (lipopolysaccharides and lipoproteins) and degradative effects of secreted bacterial proteases. Host-derived matrix metalloproteinases (MMPs) are key enzymes both in tissue homeostasis and tissue destruction. MMP expression is modulated in part by specific proteolytic fragments of fibronectin (FN), which are associated with periodontal disease. FN is a predominant extracellular matrix component in the periodontium. We examined the abil...
Research Interests: Biology, Medicine, Extracellular Matrix, Gene Silencing, Biological Sciences, and 12 moreInfection and immunity, Humans, Protease, Infection, Periodontal Ligament, Fibronectin, Proteases, Gene Expression Regulation, Treponema Denticola, Matrix Metalloproteinase, Chymotrypsin, and Medical and Health Sciences
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and... more
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated ...
Research Interests: Oncology, Immunology, Biology, Survival Analysis, Immunohistochemistry, and 13 moreTreatment Outcome, Medicine, Toll like receptor signaling, Humans, Female, Male, Middle Aged, Oral Squamous Cell Carcinoma (OSCC), Adult, Prognosis, Papillomaviridae, Papillomavirus Infections, and Head and neck neoplasms
Medical imaging often presents objects in three-dimensional (3D) form to provide better visual understanding. In contrast, histopathology is typically presented as two-dimensional (2D). Our objective was to present the tumor dimensions in... more
Medical imaging often presents objects in three-dimensional (3D) form to provide better visual understanding. In contrast, histopathology is typically presented as two-dimensional (2D). Our objective was to present the tumor dimensions in 3D by creating a 3D digital model of it and so demonstrate the location of the tumor and the histological slices within the surgical soft tissue resection specimen. We developed a novel method for modeling a tongue squamous cell carcinoma using commonly available instruments. We established our 3D-modeling method by recognizing and solving challenges that concern the selection of the direction of histological slices. Additional steps to standard handling included scanning the specimen prior to grossing and modeling the carcinoma, which required only a table scanner and modeling software. We present challenges and their solutions in modeling the resection specimen and its histological slices. We introduce a finished 3D model of a soft tissue resecti...
Research Interests: Pathology, Computer Science, Medical Sciences, Surgery, Medical Education, and 15 moreCancer, Computer Aided Design, Medicine, Additive Manufacturing, General Surgery, Oral and Maxillofacial Surgery, Histopathology, Medicina, Medicine and Surgery, Diagnostics, Tongue, Medical Surgery, Soft Tissue, Three dimensional Reconstruction, and Cancers
Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related death globally, and, despite improvements in diagnostics and treatment, survival remains poor. Matrix metalloproteinases (MMPs) are enzymes involved in... more
Pancreatic ductal adenocarcinoma (PDAC) is a significant cause of cancer-related death globally, and, despite improvements in diagnostics and treatment, survival remains poor. Matrix metalloproteinases (MMPs) are enzymes involved in stroma remodelling in inflammation and cancer. MMP-8 plays a varied prognostic role in cancers of the gastrointestinal tract. We examined the prognostic value of MMP-8 immunoexpression in tumour tissue and the amount of MMP-8-positive polymorphonuclear cells (PMNs) in PDAC and their association with immune responses using C-reactive protein (CRP) as a marker of systemic inflammation. Tumour samples from 141 PDAC patients undergoing surgery in 2002–2011 at the Department of Surgery, Helsinki University Hospital were stained immunohistochemically, for which we evaluated MMP-8 expression in cancer cells and the amount of MMP-8-positive PMNs. We assessed survival using the Kaplan–Meier analysis while uni- and multivariable analyses relied on the Cox proporti...
Research Interests:
Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality... more
Although patients with early-stage oral tongue squamous cell carcinoma (OTSCC) show better survival than those with advanced disease, there is still a number of early-stage cases who will suffer from recurrence, cancer-related mortality and worse overall survival. Incorporation of an immune descriptive factor in the staging system can aid in improving risk assessment of early OTSCC. A total of 290 cases of early-stage OTSCC re-classified according to the American Joint Committee on Cancer (AJCC 8) staging were included in this study. Scores of tumor-infiltrating lymphocytes (TILs) were divided as low or high and incorporated in TNM AJCC 8 to form our proposed TNM-Immune system. Using AJCC 8, there were no significant differences in survival between T1 and T2 tumors (p > 0.05). Our proposed TNM-Immune staging system allowed for significant discrimination in risk between tumors of T1N0M0-Immune vs. T2N0M0-Immune. The latter associated with a worse overall survival with hazard ratio...
Research Interests: Oncology, Cancer, Medicine, Survival, Internal Medicine, and 3 moreImmune system, Tongue, and Cancers
Research Interests:
Purpose We assessed the treatment outcome and the benefits of routine follow-up visits in T1 glottic laryngeal squamous cell carcinoma (LSCC). Methods Medical records of patients diagnosed with stage T1 glottic LSCC (N = 303) in five... more
Purpose We assessed the treatment outcome and the benefits of routine follow-up visits in T1 glottic laryngeal squamous cell carcinoma (LSCC). Methods Medical records of patients diagnosed with stage T1 glottic LSCC (N = 303) in five Finnish university hospitals between 2003 and 2015 were reviewed. Moreover, data from the Finnish Cancer Registry and the Population Register Center were collected. Results Of all 38 recurrences, 26 (68%) were detected during a routine follow-up visit, and over half (21 of 38, 55%) presented without new symptoms. Primary treatment method (surgery vs. radiotherapy) was not connected with 5-year disease-specific survival (DSS) or laryngeal preservation rate. Conclusion The majority of recurrences were detected on a routine follow-up visit, and local recurrences often presented without new symptoms. Routine post-treatment follow-up of T1 glottic LSCC seems beneficial. Trial registration Trial registration number and date of registration HUS/356/2017 11.12....
Research Interests:
Introduction: The liver metastases of colorectal cancer (CRC) can be surgically treated in selected cases, with continuously improving results. Matrix metalloproteinases (MMPs) contribute to cancer invasion by degrading the extracellular... more
Introduction: The liver metastases of colorectal cancer (CRC) can be surgically treated in selected cases, with continuously improving results. Matrix metalloproteinases (MMPs) contribute to cancer invasion by degrading the extracellular matrix, and elevated levels of MMP-2, MMP-8, and MMP-9 have been detected in several malignancies. Myeloperoxidase (MPO) is a mediator of tissue damage that can oxidatively activate latent MMPs. We evaluated the prognostic value of MMP-2, MMP-8, and MMP-9 in tissue samples of primary tumors and liver metastases and the pre- and postoperative serum levels of MMP-8, MMP-9, and MPO in CRC patients undergoing liver resection. Methods: Tissue and serum samples were obtained from 111 patients who had primary colorectal tumors and their liver metastases surgically treated at the Helsinki University Hospital between 1988 and 2007. Tissue expression of MMP-2, MMP-8, and MMP-9 in primary tumors and liver metastases was evaluated by immunohistochemistry. Pre- ...
Research Interests:
Better visualization of tumor structure and orientation are needed in the postoperative setting. We aimed to assess the feasibility of a system in which oral and oropharyngeal tumors are resected, photographed, 3D modeled, and printed... more
Better visualization of tumor structure and orientation are needed in the postoperative setting. We aimed to assess the feasibility of a system in which oral and oropharyngeal tumors are resected, photographed, 3D modeled, and printed using additive manufacturing techniques. Three patients diagnosed with oral/oropharyngeal cancer were included. All patients underwent preoperative magnetic resonance imaging followed by resection. In the operating room (OR), the resected tissue block was photographed using a smartphone. Digital photos were imported into Agisoft Photoscan to produce a digital 3D model of the resected tissue. Physical models were then printed using binder jetting techniques. The aforementioned process was applied in pilot cases including carcinomas of the tongue and larynx. The number of photographs taken for each case ranged from 63 to 195. The printing time for the physical models ranged from 2 to 9 h, costs ranging from 25 to 141 EUR (28 to 161 USD). Digital photogra...
Research Interests:
Research Interests:
Research Interests: Dentistry, Cancer, Recognition, Immunohistochemistry, Medicine, and 13 moreToll like receptor signaling, HUMAN PAPILLOMAVIRUS, Internal Medicine, Epidemic, Oral Oncology, Expression, Head, Progression, Carcinogenesis, Public health systems and services research, Cancers, PORPHYROMONAS GINGIVALIS, and Treponema Denticola
Human β-defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the... more
Human β-defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remain unknown. We, therefore, investigated the role of hBD2–histamine crosstalk signaling in promoting OLP pathology. Biopsies from OLP and oral tongue squamous cell carcinoma (OTSCC) patients, and healthy controls were used. Two OTSCC cell lines and normal human oral keratinocytes (HOKs) were used. HBD-2 and other targets were mapped by immunostaining and analyzed by ImageJ2 software. The highly sensitive droplet-digital PCR technology and qRT-PCR were utilized to study the clinically derived and in vitro samples, respectively. H4R was challenged with the specific agonist HST-10 and inverse agonist ST-1007. HBD-2 was highly induced in OLP les...
Research Interests:
Hormone receptors play an important role in many types of cancers. Alongside factors associated with human papillomavirus (HPV) infection, hormonal receptors may impact the tumorigenesis of oropharyngeal cancer. This study consists of 199... more
Hormone receptors play an important role in many types of cancers. Alongside factors associated with human papillomavirus (HPV) infection, hormonal receptors may impact the tumorigenesis of oropharyngeal cancer. This study consists of 199 consecutive oropharyngeal squamous cell carcinoma (OPSCC) patients diagnosed and treated with a curative intent. We examined androgen (AR), estrogen (ER; both alpha and beta), and progesterone receptor (PR) expressions using immunohistochemistry comparing tumor and patient characteristics. AR was expressed in 16%, PR in 27% and ER-beta in 63% of the tumors. HPV- and p16-positive tumors expressed more AR and less PR than their negative counterparts. High PR expression was associated with poor disease-specific and locoregional recurrence-free survival. AR, PR, and ER-beta are expressed in OPSCC, and AR and PR expressions are associated with HPV and p16 status. Furthermore, PR appears to have prognostic significance. This may allow us to investigate t...
Research Interests: Immunohistochemistry, Medicine, Estrogen Receptor, HUMAN PAPILLOMAVIRUS, Humans, and 15 moreInternal Medicine, Female, Male, HPV, Clinical Sciences, Aged, Middle Aged, Carcinogenesis, Hormone, Prognosis, Androgen Receptor, Progesterone receptors, Papillomavirus Infections, Head and neck neoplasms, and Oropharynx
Oral tongue squamous cell carcinoma (OTSCC) has a relatively poor outcome and there is a need to identify better prognostic factors. Recently, tumour-stroma ratio (TSR) has been associated with prognosis in several cancers. This... more
Oral tongue squamous cell carcinoma (OTSCC) has a relatively poor outcome and there is a need to identify better prognostic factors. Recently, tumour-stroma ratio (TSR) has been associated with prognosis in several cancers. This multi-institutional study evaluates the prognostic value of TSR from original HE-stained tumor-resection slides in a series of early-stage (cT1-2N0) OTSCC patients. A TSR cutoff value of 50% was used to divide the patients into stroma-rich (≥50%) and stroma-poor (<50%) groups. The relationships between TSR and clinicopathologic characteristics of 311 early-stage OTSCC cases were analyzed. The prognostic value of TSR in OTSCC was calculated separately and in combination with a previously published cancer cell budding and depth of invasion (BD) prognostic model. A total of 89 cases (28.6%) belonged to the stroma-rich group. In a multivariate analysis, the stroma-rich group had worse disease-free survival with a hazard ratio (HR) of 1.81 (95%CI 1.17-2.79, P=...
Research Interests:
Research Interests:
The purpose of the study was to evaluate the long-term outcome of minor salivary and mucous gland (MiSG) adenoid cystic carcinoma (ACC) of the head and neck and to compare the results with earlier reports including our recently published... more
The purpose of the study was to evaluate the long-term outcome of minor salivary and mucous gland (MiSG) adenoid cystic carcinoma (ACC) of the head and neck and to compare the results with earlier reports including our recently published series on major salivary gland (MaSG) ACC. The study comprised 68 MiSG ACCs operated during 1974-2012 at the Helsinki University Hospital, Helsinki, Finland. Medical records and histological samples were reviewed. Our previously published cohort comprising 54 MaSG ACCs during the years from 1974 to 2009 was used for comparison. The most common locations were the oral cavity and sinonasal cavities. Most patients presented stages IV (33.8%) and I (23.5%) disease. Primary treatment with curative intent, mainly surgery, was offered for 64 patients. Thirty-three (51.6%) of these patients developed a disease recurrence and 22 (66.7%) patients in less than 5 years. The difference in the length of recurrence-free time (<5 vs. >5 years) had an impact o...
Research Interests:
Research Interests: Cancer, Biology, Cancer Research, Medicine, Western blotting, and 13 moreToll Like Receptors, Humans, Cell, Polymerase Chain Reaction, Clinical Sciences, In Vivo, Oral Squamous Cell Carcinoma (OSCC), Prognosis, Tumor Biology, Cell Proliferation, Case Control Studies, Papillomaviridae, and Papillomavirus Infections
This study aims to evaluate the long-term outcome of major salivary gland adenocystic carcinoma (ACC). This is a retrospective review of 54 cases of ACC during a 35-year period from 1974 to 2009 at the Helsinki University Central... more
This study aims to evaluate the long-term outcome of major salivary gland adenocystic carcinoma (ACC). This is a retrospective review of 54 cases of ACC during a 35-year period from 1974 to 2009 at the Helsinki University Central Hospital, Helsinki, Finland. Medical records and histological samples were reviewed. All patients had a minimum follow-up time of 5 years or until death. Most of the tumours occurred in the parotid gland (n = 30, 56 %) followed by submandibular gland (n = 22, 41 %) and sublingual gland (n = 2, 4 %). Fifty-two patients (96 %) were treated with curative intent. All of these patients except one were primarily treated with surgery, and 29 patients (54 %) also received postoperative radiotherapy for their primary tumour. Two patients (4 %) received palliative radiotherapy. For those treated with curative intent, 32 patients (62 %) had disease recurrence. Twenty-four patients (75 %) had their first disease recurrence within 5 years and eight patients (25 %) later...
Research Interests:
Despite early diagnosis and treatment, almost 20 % of patients with early-stage (cT1-cT2N0) oral tongue squamous cell carcinoma (OTSCC) still die of their disease. The prognosis of OTSCC patients is influenced by several demographic,... more
Despite early diagnosis and treatment, almost 20 % of patients with early-stage (cT1-cT2N0) oral tongue squamous cell carcinoma (OTSCC) still die of their disease. The prognosis of OTSCC patients is influenced by several demographic, clinical, and histopathologic factors. The aim of this multicenter international study was to find which of the factors age, gender, stage, grade, lymphocytic host response, perineural invasion, worst pattern of invasion, or depth of invasion has the strongest prognostic power in early-stage OTSCC. Patient data of 479 patients with early-stage (cT1-2N0) OTSCC in Finland, Brazil, and the USA were retrieved and analyzed using Cox proportional hazards regression models. Our results indicate that depth of invasion (DOI) and worst pattern of invasion (WPOI) are the strongest pathological predictors for locoregional recurrence, with a hazard ratio (HR) for 4 mm DOI of 1.67 (95 % confidence interval (CI) 1.07-2.60) and HR for WPOI of 1.46 (95 % CI 0.95-2.25). ...
Research Interests: Cancer, Adolescent, Medicine, Humans, Child, and 15 moreFemale, Male, Squamous Cell Carcinoma, Clinical Sciences, Aged, Middle Aged, Neoplasm Invasiveness, Adult, Proportional hazards model, Proportional Hazards Models, Confidence Interval, Pathological, Neoplasm staging, Head and neck neoplasms, and Perineural invasion
Podocalyxin (PODXL) is a transmembrane sialomucin, whose aberrant expression and/or allelic variation associates with poor prognosis and unfavourable clinicopathological characteristics in different cancers. Membranous expression of PODXL... more
Podocalyxin (PODXL) is a transmembrane sialomucin, whose aberrant expression and/or allelic variation associates with poor prognosis and unfavourable clinicopathological characteristics in different cancers. Membranous expression of PODXL has been suggested to be an independent marker of poor prognosis in colorectal cancer (CRC), and previously by an in-house monoclonal antibody, we showed that also cytoplasmic overexpression of PODXL predicts poor prognosis. The aim of this study was to compare two PODXL antibodies with different epitopes case-by-case in CRC patients. Of 840 consecutively operated CRC patients from Helsinki University Central Hospital, PODXL expression by polyclonal HPA 2110 antibody was evaluated from 780. Associations of PODXL expression with clinicopathological parameters and the impact of PODXL expression on survival were assessed. Kappa-value was used to assess the comparability of the two antibodies. Membranous PODXL expression associated with unfavourable cl...
Research Interests:
Over two decades ago, a proposal was that two different colorectal cancer (CRC) entities existed, based on tumour location either proximal (right) or distal (left) of the splenic flexure. Proximal and distal tumours exhibit different... more
Over two decades ago, a proposal was that two different colorectal cancer (CRC) entities existed, based on tumour location either proximal (right) or distal (left) of the splenic flexure. Proximal and distal tumours exhibit different clinical, epidemiological, and biological characteristics. Improvement of the prognostic evaluation of CRC requires new molecular markers. Podocalyxin-like 1 (PODXL), an anti-adhesive transmembrane sialomucin, is associated with an aggressive tumour phenotype and poor prognosis. For colorectal cancer, it has been suggested to be a marker of poor prognosis. The aim of this study was to investigate the role of PODXL in CRC by use of a novel monoclonal antibody. In 1983-2001, 840 consecutive colorectal cancer patients were treated at Helsinki University Central Hospital, of whom 767 were successfully scored for PODXL immunohistochemical expression from tumour tissue microarrays by use of a novel monoclonal in-house antibody. Associations of PODXL expressio...
Research Interests:
The prognosis of squamous cell carcinoma of the oral tongue is poor and it would be beneficial to find prognostic markers to better adjust treatment. Bmi-1 controls cell cycle and self-renewal of tissue stem cells, transcription factor... more
The prognosis of squamous cell carcinoma of the oral tongue is poor and it would be beneficial to find prognostic markers to better adjust treatment. Bmi-1 controls cell cycle and self-renewal of tissue stem cells, transcription factor c-myc affects cell proliferation and apoptosis, and Snail regulates epithelial-mesenchymal transition. The expression of these markers has been connected to prognosis in many cancer types. Bmi-1, c-myc, and Snail expressions were studied in our material consisting of 73 primarily T1N0M0 oral tongue carcinoma patients. We compared the immunoexpressions of Bmi-1, c-myc, and Snail with clinical parameters including the degree of histological differentiation, tumour size, TNM classification, depth of invasion, and resection margins. In addition, survival analyses were performed, comparing disease-free survival time with the registered protein expression of the markers mentioned above. A significant correlation between Bmi-1 protein expression and recurren...
Research Interests:
Research Interests: Dentistry, Migration, Biology, Immunohistochemistry, Cancer Research, and 15 moreMedicine, Cell Differentiation, Humans, Female, Male, Squamous Cell Carcinoma, Aged, Middle Aged, Oral Squamous Cell Carcinoma (OSCC), Neoplasm Invasiveness, Adult, Prognosis, Matrix Metalloproteinase, Tongue neoplasms, and Head and neck neoplasms
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Oral lichen planus (OLP) is an oral counterpart or oral manifestation of the common skin disease lichen planus. Chronic junctional stomatitis (CJS) is a relatively unknown condition characterized by a stromal lymphocyte infiltrate, which... more
Oral lichen planus (OLP) is an oral counterpart or oral manifestation of the common skin disease lichen planus. Chronic junctional stomatitis (CJS) is a relatively unknown condition characterized by a stromal lymphocyte infiltrate, which is also a diagnostic feature of OLP. The differential diagnosis of OLP and CJS is unclear and they have been suggested to represent variants of the same disease. To investigate possible differences in lymphocyte (sub)populations between these two conditions, we immunostained 10 OLP and 10 CJS specimens for CD1-a, and the lymphocyte markers, CD3, CD4, CD5, CD8, and CD20. We scored the staining results by a four-step grading system and used the Fisher exact test to analyze them statistically. The proportional amount of (CD20 positive) B lymphocytes was higher in CJS than in OLP and the predominance of CD4 positive T lymphocytes over CD8 positive T lymphocytes was stronger in OLP than in CJS. The differences were statistically significant. The results reflect differences in the lymphatic infiltrate between OLP and CJS. Their significance needs further investigation.
Research Interests:
Oral squamous cell carcinoma (OSCC) has a worse prognosis than cutaneous squamous cell carcinoma (CSCC). Toll-like receptor- 4 (TLR-4) and TLR-5 are transmembrane proteins that recognize endogenous and microbial agents. Their activation... more
Oral squamous cell carcinoma (OSCC) has a worse prognosis than cutaneous squamous cell carcinoma (CSCC). Toll-like receptor- 4 (TLR-4) and TLR-5 are transmembrane proteins that recognize endogenous and microbial agents. Their activation has been connected to cancer invasion. The aim was to study the expression of TLR-4 and TLR-5 in OSCC and CSCC samples, and the effects of TLR-5 ligand flagellin on the proliferation, migration, and invasion of different mucocutaneous cell lines in vitro. Samples of early-stage tumors (T1-T2N0M0) from 63 patients with OSCC and CSCC were obtained, in addition to eight normal mucosa and skin tissues from healthy subjects. Oral-cavity-derived highly aggressive HSC-3, less invasive SAS, and HPV-transformed benign IHGK as well as C-ha-ras-transformed (HaCat) skin carcinoma II-4 and non-invasive A5 cell lines were used. Flagellin-induced mucocutaneous cell lines were compared by using BrdU-proliferation, scratch migration, and myoma organotypic invasion assays. TLR-4 expression was similar in OSCC and CSCC tumors. TLR-5 was more abundant in OSCC than in CSCC samples. Flagellin induced the proliferation of SAS, II-4 and A5, migration of IHGK, II-4 and A5, and the invasion of II-4 cells. It had no effect on HSC-3 cells. Flagellin, a TLR-5 agonist, induced the migration and invasion of less aggressive mucocutaneous cell lines, but it had no effect on the most invasive oral carcinoma cells. The more aggressive clinical behavior of OSCC compared to CSCC may partially be related to the differences in the expression of TLR-5 in these malignancies.
Research Interests: Dentistry, Biology, Immunohistochemistry, Cancer Research, Medicine, and 12 moreToll like receptor signaling, Humans, Aged, Middle Aged, Oral Squamous Cell Carcinoma (OSCC), Neoplasm Invasiveness, Mouth Neoplasms, Cell Proliferation, Case Control Studies, Flagellin, Skin Neoplasms, and Head and neck neoplasms
Research Interests:
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and... more
A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated ...
Research Interests:
Toll-like receptors (TLRs) are important in barrier homeostasis, but their role in airborne allergies is not fully understood. The aim was to evaluate baseline and allergen-induced expression of TLR proteins in nasal epithelium during... more
Toll-like receptors (TLRs) are important in barrier homeostasis, but their role in airborne allergies is not fully understood. The aim was to evaluate baseline and allergen-induced expression of TLR proteins in nasal epithelium during allergic rhinitis. Nineteen otherwise healthy non-smoking volunteers both allergic to birch pollen and non-allergic controls were enrolled. We took nasal biopsies before and after off-seasonal intranasal birch pollen or diluent challenge. The expression of epithelial TLR1-7, TLR9-10, and MyD88 proteins was immunohistochemically evaluated from the nasal biopsies. The TLR1-3 and TLR5-10 mRNAs were observed by RNA-microarray. Baseline epithelial expression of TLR proteins was wide and identical in controls and atopics. After off-seasonal intranasal birch pollen challenge, a negative change in the expression score of TLR1 and TLR6 proteins was detected in the atopic group. TLR mRNA expression was not affected by birch pollen challenge. Nasal epithelium seems to express all known TLRs. The mechanisms by which TLR1, and TLR6 proteins could affect pollen allergen transport need further studies.
Research Interests:
We sought to clarify whether the expression of toll-like receptors (TLR) in Merkel cell carcinoma (MCC) is linked to tumor and patient characteristics, especially the presence of Merkel cell polyoma virus (MCV). The study comprised of 128... more
We sought to clarify whether the expression of toll-like receptors (TLR) in Merkel cell carcinoma (MCC) is linked to tumor and patient characteristics, especially the presence of Merkel cell polyoma virus (MCV). The study comprised of 128 patients with data on Merkel cell polyomavirus (MCV) status and clinical features were included in the study. Immunohistochemistry for TLR expression was performed on tissue microarray (TMA) slides. TLR 2, 4, 5, 7 and 9 expression was noted in most of the tumor specimens. Decreased expression of TLR 9 correlated strongly with MCV positivity. Cytoplasmic TLR 2 expression correlated with small tumor size, while nuclear TLR 2 and TLR 5 expressions with larger tumors. Increased nuclear TLR 4 expression and decreased TLR 7 expression were associated with older age. TLR 2, 4, 5, 7 and 9 appear to reflect certain clinicopathological variables and prognostic markers of MCC tumors.
Research Interests:
Since benign and malignant mucin-producing tumors of the pancreas may be difficult to distinguish from each other; preoperative methods for differential diagnosis would reduce unnecessary surgery. To compare syndecan-1 and tenascin... more
Since benign and malignant mucin-producing tumors of the pancreas may be difficult to distinguish from each other; preoperative methods for differential diagnosis would reduce unnecessary surgery. To compare syndecan-1 and tenascin immunoexpression in benign and malignant cystic pancreatic tumors. We used immunohistochemical staining for syndecan-1 and tenascin antibodies in tumor tissue samples. Helsinki University Central Hospital. Tissue material came from 33 patients undergoing surgery from 1979 to 2005 for cystic pancreatic tumors. A statistically significant difference appeared in syndecan-1 expression between benign (mucinous cystic neoplasms and intraductal papillary mucinous neoplasms) and mucinous carcinomas, but there was no significant difference in tenascin immunoexpression between these tumor groups. Our findings suggest that low syndecan-1 expression might serve as a predictive factor for malignancy in cystic tumors of the pancreas.
Research Interests:
All human cells are covered by glycans, the carbohydrate units of glycoproteins, glycolipids, and proteoglycans. Most glycans are localized to cell surfaces and participate in events essential for cell viability and function.... more
All human cells are covered by glycans, the carbohydrate units of glycoproteins, glycolipids, and proteoglycans. Most glycans are localized to cell surfaces and participate in events essential for cell viability and function. Glycosylation evolves during carcinogenesis, and therefore carcinoma-related glycan structures are potential cancer biomarkers. Colorectal cancer is one of the world's three most common cancers, and its incidence is rising. Novel biomarkers are essential to identify patients for targeted and individualized therapy. We compared the N-glycan profiles of five rectal adenomas and 18 rectal carcinomas of different stages by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry. Paraffin-embedded tumor samples were deparaffinized, and glycans were enzymatically released and purified. We found differences in glycosylation between adenomas and carcinomas: monoantennary, sialylated, pauci-mannose, and small high-mannose N-glycan structures wer...
Research Interests:
The prognosis of squamous cell carcinoma of the oral tongue is poor and it would be beneficial to find prognostic markers to better adjust treatment. Bmi-1 controls cell cycle and self-renewal of tissue stem cells, transcription factor... more
The prognosis of squamous cell carcinoma of the oral tongue is poor and it would be beneficial to find prognostic markers to better adjust treatment. Bmi-1 controls cell cycle and self-renewal of tissue stem cells, transcription factor c-myc affects cell proliferation and apoptosis, and Snail regulates epithelial-mesenchymal transition. The expression of these markers has been connected to prognosis in many cancer types. Bmi-1, c-myc, and Snail expressions were studied in our material consisting of 73 primarily T1N0M0 oral tongue carcinoma patients. We compared the immunoexpressions of Bmi-1, c-myc, and Snail with clinical parameters including the degree of histological differentiation, tumour size, TNM classification, depth of invasion, and resection margins. In addition, survival analyses were performed, comparing disease-free survival time with the registered protein expression of the markers mentioned above. A significant correlation between Bmi-1 protein expression and recurren...
Research Interests: Cell Cycle, Immunohistochemistry, Stem Cell, Transcription Factors, Epithelial-Mesenchymal Transition, and 16 moreHumans, Female, Male, Squamous Cell Carcinoma, Young Adult, Follow-up studies, Oral Cancer, Transcription Factor, Aged, Middle Aged, Oral Squamous Cell Carcinoma (OSCC), Adult, Survival Rate, Prognosis, Protein Expression, and Cell Proliferation
Research Interests:
Mechanisms of the dentigerous cyst formation from the normal eruption follicle is unknown but disturbances in the proteolytic activity have been suspected, since the growth of these cysts is accompanied by local bone destruction. The aim... more
Mechanisms of the dentigerous cyst formation from the normal eruption follicle is unknown but disturbances in the proteolytic activity have been suspected, since the growth of these cysts is accompanied by local bone destruction. The aim of the present study was to evaluate the expression of matrix metalloproteinases (MMP) in human dental dentigerous cysts and healthy dental follicles. We studied 10 patients with dentigerous cysts and 10 healthy dental follicles from the lower jaw in respect to their immunoexpression of MMPs -8, -9, -25, and -26 and tissue inhibitor of metalloproteinases -1 (TIMP-1). MMP-8 was expressed slightly more in cyst epithelium than in odontogenic epithelium of healthy controls dental follicle but the difference lacked statistical difference. Other MMPs and TIMP-1 did not differ regarding the studied specimens. Differences in MMP expression cannot solely explain the cyst expansion suggesting the potential involvement of other osteolytic mechanisms.
Research Interests:
Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascular tumour, occurring almost exclusively in adolescent males. Histogenesis of JNA remains unclear, two optional theories proposing either fibrous or vascular tissue as the tissue... more
Juvenile nasopharyngeal angiofibroma (JNA) is a highly vascular tumour, occurring almost exclusively in adolescent males. Histogenesis of JNA remains unclear, two optional theories proposing either fibrous or vascular tissue as the tissue of origin. Stem cell-related proteins have been discussed to possibly participate in the growth of these tumours. In our study, we reviewed retrospective clinicopathological data of 26 JNA patients. By immunohistochemistry, we investigated the cellular distribution and expression levels of stem cell-related proteins C-KIT, C-MYC and BMI-1 and their correlation with cell and vessel density of the tumour. Contrary to earlier reports, we detected C-KIT expression in addition to stromal cells also in endothelial cells. The C-KIT expression was more dominant in slit vessels than large vessels. A significant correlation was found between endothelial immunoexpression of C-KIT and cellular density of the tumour. C-MYC and BMI-1 expression was detected in stromal cells only. Due to our finding of C-KIT expression in both stromal and endothelial cells and the strong correlation between the endothelial C-KIT expression and cellular density, we suggest that, besides the stromal tissue, the vascular component might take part in the neoplastic growth of JNA.
Research Interests:
Matrix metalloproteinase-7 is capable of degrading many extracellular matrix proteins and cellular adhesions. In many malignancies, it is overexpressed, and it plays a role in cancer progression by enhancing tumor invasion and thereby... more
Matrix metalloproteinase-7 is capable of degrading many extracellular matrix proteins and cellular adhesions. In many malignancies, it is overexpressed, and it plays a role in cancer progression by enhancing tumor invasion and thereby metastatic potential. The purpose of this study was to evaluate the association between MMP-7 tissue expression and prognosis in colorectal cancer. From 623 patients who underwent surgery for colorectal cancer, surgical specimens were collected into tissue array blocks and stained by immunohistochemistry for MMP-7. Specimens from 545 patients were suitable for analysis. In specimens from 105 patients (19.3%), MMP-7 scored as high; in 103 (18.9%), as moderate; and in 134 (24.9%), as mild. In 203 cases (37.2%), immunoreactivity was negative. A significant correlation appeared between MMP-7 immunoexpression and tumor differentiation. High MMP-7 positivity associated with poor prognosis during a 5-year follow-up. During longer follow-up, the differences in survival between groups disappeared. MMP-7 is a potential target for tumor therapy, which should be evaluated in clinical trials.
Research Interests: Clinical Trial, Immunohistochemistry, Colorectal cancer, Humans, Female, and 12 moreMale, Follow-up studies, Clinical Sciences, Aged, Retrospective Studies, Prognosis, Disease Progression, Tumor Biology, Adenocarcinoma, Extracellular Matrix Proteins, Matrix Metalloproteinase, and Colorectal Neoplasms
Well-differentiated follicular thyroid carcinomas (FTCs) usually act indolently, while aggressively acting tumors are difficult to detect early enough. Estrogen receptors (ERs) have prognostic significance in many cancers. Thyroid... more
Well-differentiated follicular thyroid carcinomas (FTCs) usually act indolently, while aggressively acting tumors are difficult to detect early enough. Estrogen receptors (ERs) have prognostic significance in many cancers. Thyroid diseases, including neoplasms, are associated with the female sex. The prognostic significance of ERs in FTCs has not been reported previously. We studied the role of ERα and ERβ in 83 cases of follicular thyroid adenoma (FTA) and 43 FTC cases, including seven cases of poorly differentiated FTC, obtained from the Department of Surgery, Helsinki University Central Hospital between 1990 and 2009. Patient follow-up was conducted until March 2011. Expression of ERα, ERβ, and MIB-1/Ki-67 was investigated by immunohistochemistry and correlated with clinicopathological characteristics, including survival. Two major observations were apparent. First, ERβ expression was significantly higher in FTA than in FTC, and it was a stronger differential diagnostic marker than MIB-1/Ki-67. Second, low ERβ expression correlated with poor survival in FTC. All cancer-specific deaths due to FTC were among low ERβ-score patients. ERβ is a differential marker for malignancy and could thus be used as a preoperative tool. FTC patients with a low ERβ score need more thorough follow-up and may benefit from more aggressive treatment.