Search

Uroplakin 3B (Upk3b) is involved in stabilizing and strengthening the urothelial cell layer of the bladder. Based on RNA expression studies, Upk3b is expressed in a limited number of normal and tumor tissues. The potential use of Upk3b as a diagnostic or prognostic marker in tumor diagnosis has not yet been extensively investigated. A tissue microarray containing 17,693 samples from 151 different tumor types/subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry. In normal tissues, Upk3b expression was largely limited to mesothelial cells, urothelial umbrella cells, and amnion cells. In tumor tissues, Upk3b was detectable in only 17 of 151 (11.3%) of tumor types. Upk3b expression was most frequent in mesotheliomas (82.1% of epithelioid and 30.8% of biphasic) and in urothelial tumors of the urinary bladder, where the positivity rate decreased from 61.9% in pTaG2 (low grade) to 58.0% in pTaG3 (high grade) and 14.6% in pT2-4 cancers. Among pT2-4 urothelial carcinomas, Upk3b staining was unrelated to tumor stage, lymph node status, and patient prognosis. Less commonly, Upk3b expression was also seen in Brenner tumors of the ovary (10.8%), as well as in four other subtypes of ovarian cancer (0.9–10.6%). Four additional tumor entities showed a weak to moderate Upk3b positivity in less than 5% of cases. In summary, Upk3b immunohistochemistry is a useful diagnostic tool for the distinction of mesotheliomas from other thoracic tumors and the visualization of normal mesothelial and umbrella cells.

As a result of its expression in corresponding normal cell types, inhibin alpha (INHA) is used as an immunohistochemical marker for adrenocortical neoplasms and testicular or ovarian sex cord stromal tumors. However, other tumors can also express INHA. To comprehensively determine INHA expression in cancer, a tissue microarray containing 15,012 samples from 134 different tumor types and subtypes was analyzed by immunohistochemistry. INHA positivity was found in 72 of 134 tumor categories, including 26 categories with ≥1 strongly positive case. A moderate to strong INHA positivity was found in 100% of 37 granulosa cell tumors of the ovary, 100% of 43 other sex cord stromal tumors of the ovary/testis, 100% of 31 granular cell tumors, 78.5% of 28 adenomas, 44% of 25 carcinomas of the adrenal cortex, and 46.7% of 15 pancreatic acinar cell carcinomas. At least a weak INHA positivity was seen in

Background Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis. Methods A tissue microarray made from 17,747 individual cancer samples with comprehensive, pathological, clinical and molecular data was analyzed by immunohistochemistry for ESRP1 and ESRP2. Results Nuclear staining for ESRP1 was seen in 38.6% (36.0% low, 2.6% high) of 12,140 interpretable cancers and in 41.9% (36.4% low, 5.3% high) of 12,962 interpretable cancers for ESRP2. Nuclear protein expression was linked to advanced tumor stage, high Gleason score, presence of lymph node metastasis, early biochemical recurrence, and ERG-positive cancers (p Conclusions Our data show a striking link between nuclear ESRP expression and adverse features in prostate cancer and identifies expression of ESRP1 and/or ESRP2 as independent prognostic markers with a potential for routine application.

Background and objectives Overexpression of the cytoskeleton-modulating kinase ROCK1 has been associated with unfavorable outcome in many cancers, but its impact in prostate cancer is largely unknown. Results A weak ROCK1 staining was found in >90% of normal, and cancerous prostate tissues, but was generally stronger in cancer cells as compared to adjacent normal glands. In cancer, ROCK1 staining was considered weak, moderate, and strong in 22%, 53%, and 18% of cases respectively. Higher ROCK1 expression levels were associated with tumor stage, and Gleason grade, positive nodal stage, positive surgical margin, accelerated cell proliferation and early PSA recurrence in multivariable analysis. ROCK1 up regulation was associated with androgen receptor (AR) expression, TMPRSS2:ERG fusion, genomic deletions of the PTEN tumor suppressor, as well as recurrent deletions at chromosomes 3p, 5q, 6q. Strong ROCK1 staining was found in 3% of AR-negative, but in 27% of strongly AR positive cancers, in 13% of ERG-negative but in 25% of ERG positive cancers, and in 12% of PTEN normal but in 26% of PTEN deleted cancers. Conclusions This study identifies ROCK1 expression associated with prognosis in prostate cancer. Methods We tested ROCK1 expression in 12 427 prostate cancer specimens and followed PSA recurrence after prostatectomy.

Within the concert of immune reactions against tumour cells cytotoxic and regulatory T-cells are of utmost importance. Several studies revealed contradictory results on this issue. We therefore focused on functional expression patterns and localization of tumour-infiltrating T-lymphocytes in non-small cell lung cancer (NSCLC) and their impact on patient's survival. 232 curatively operated NSCLC patients were included. After histological reevaluation and construction of tissue-multi-arrays immunohistochemical doublestains for CD3/CD8 and CD4/CD25 were performed to evaluate the total number of T-cells and their subsets of cytotoxic and activated T-cells. Additionally, the localization of the lymphocytes was included in the analysis. Hereby, T-cells within the tumour stroma were regarded as stromal, those among cancer cells as intraepithelial. The number of lymphocytes differed significantly between the histological subtypes being most prominent in large cell carcinomas. Survival analysis showed that high numbers of stromal T-lymphocytes are of beneficial prognostic influence in NSCLC patients. This also proved to be an independent prognostic factor in adenocarcinomas. Thus, in a large and well characterized cohort of NSCLC this is the first study to determine the prognostic value of stromal T-lymphocytes, as these are an independent prognosticator in NSCLC especially in adenocarcinomas whereas intraepithelial T-cells are not.

// Jiaying Zhou 1, * , Yabin Cheng 2, 3, * , Liren Tang 4 , Magdalena Martinka 5 , Sunil Kalia 3 1 Faculty of Science, University of British Columbia, Vancouver, BC, Canada 2 School of Pharmaceutical Sciences, Xiamen University, Xiamen, China 3 Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada 4 Welichem Biotech Inc, Burnaby, BC, Canada 5 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada * These authors have contributed equally to this work Correspondence to: Yabin Cheng, email: chengyb@xmu.edu.cn Sunil Kalia, email: sunil.kalia@vch.ca Keywords: SERPINA3, melanoma, AACT (alpha-1 antichymotrypsin), tissue micro array, cell migration and invasion Received: November 14, 2015 Accepted: March 28, 2016 Published: May 17, 2016 ABSTRACT Serpin Peptidase Inhibitor, clade A member 3 (SERPINA3) was found to be abnormally overexpressed in a subset of melanoma tissue biopsies. High SERPINA3 expression was also associated with poor patient survival. In this study, we set out to test SERPINA3 protein’s prognostic potential with a larger-sized and independent patient cohort, and to explore SERPINA3’s function in melanoma cells. Tissue microarray-based immunohistochemistry analysis showed a significant increase in SERPINA3 expression in invasive and metastatic melanomas compared to normal nevi and melanoma-in-situ ( P < 0.001, Chi-square test). In melanoma patients, high SERPINA3 expression was strongly associated with worse overall and disease specific survival at 5 years. Multivariate Cox regression analysis showed that SERPINA3 expression is an independent prognostic factor to predict melanoma patient clinical outcome. When SERPINA3 expression was selectively silenced using small interfering RNA molecules (siRNA) in cultured melanoma cell lines, cell migration and matrix invasion was significantly decreased, but no change in cell proliferation was observed. This study confirms the prognostic potential of SERPINA3 expression in human cutaneous melanoma and reveals the pro-migration and pro-invasion functions of this protein on melanoma cells.