Molecular profiling of ETS and non‐ETS aberrations in prostate cancer patients from northern India

BACKGROUNDMolecular stratification of prostate cancer (PCa) based on genetic aberrations including ETS or RAF gene‐rearrangements, PTEN deletion, and SPINK1 over‐expression show clear prognostic and diagnostic utility. Gene rearrangements involving ETS transcription factors are frequent pathogenetic somatic events observed in PCa. Incidence of ETS rearrangements in Caucasian PCa patients has been reported, however, occurrence in Indian population is largely unknown. The aim of this study was to determine the prevalence of the ETS and RAF kinase gene rearrangements, SPINK1 over‐expression, and PTEN deletion in this cohort.METHODSIn this multi‐center study, formalin‐fixed paraffin embedded (FFPE) PCa specimens (n = 121) were procured from four major medical institutions in India. The tissues were sectioned and molecular profiling was done using immunohistochemistry (IHC), RNA in situ hybridization (RNA‐ISH) and/or fluorescence in situ hybridization (FISH).RESULTSERG over‐expression was detected in 48.9% (46/94) PCa specimens by IHC, which was confirmed in a subset of cases by FISH. Among other ETS family members, while ETV1 transcript was detected in one case by RNA‐ISH, no alteration in ETV4 was observed. SPINK1 over‐expression was observed in 12.5% (12/96) and PTEN deletion in 21.52% (17/79) of the total PCa cases. Interestingly, PTEN deletion was found in 30% of the ERG‐positive cases (P = 0.017) but in only one case with SPINK1 over‐expression (P = 0.67). BRAF and RAF1 gene rearrangements were detected in ∼1% and ∼4.5% of the PCa cases, respectively.CONCLUSIONSThis is the first report on comprehensive molecular profiling of the major spectrum of the causal aberrations in Indian men with PCa. Our findings suggest that ETS gene rearrangement and SPINK1 over‐expression patterns in North Indian population largely resembled those observed in Caucasian population but differed from Japanese and Chinese PCa patients. The molecular profiling data presented in this study could help in clinical decision‐making for the pursuit of surgery, diagnosis, and in selection of therapeutic intervention. Prostate 75:1051–1062, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111808/1/pros22989.pd

Post chemotherapy diagnostic dilemma: A case report

Diagnostic evaluation of tumors in their posttherapeutic stage requires a meticulous approach for correct diagnosis as chemotherapy or radiotherapy often alters the tumor characteristics that vary significantly from their pretherapeutic phase. Here, we report a case of chemotherapy-received retroperitoneal lymph node deposits of metastatic testicular embryonal carcinoma that failed to express immunohistochemistry (IHC) markers employed to make diagnosis in the pretherapeutic phase. The dilemma of overdiagnosis so created was resolved by the use of added markers that probably could sustain the slaught of chemotherapy. Therefore, a judicious and diligent understanding of the use and action of IHC markers is utmost necessary to prevent such dilemmas

VHL protein expression in renal cell carcinoma

Introduction: Various studies have been performed to detect VHL gene mutation in renal cell carcinoma (RCCs) but there is paucity of literature analyzing VHL expression at the protein level. Present study was carried out to analyze VHL protein (pVHL) expression in the tissue of RCCs and its correlation with tumor grade & stage. Material and methods: Immunohistochemical detection of pVHL was done by using a mouse monoclonal antibody raised against amino acids 54-213 of VHL of human. Statistical analysis was done by using chi-square test and Kruskall Wallis H Test. Results: 32 patients of renal cell carcinoma were included in the study. pVHL expression was positive in 84.40% cases . Among all pVHL positive cases, combined cytoplasmic and nuclear expression of pVHL was most common (59.0%). Exclusive nuclear expression alone was rare and was noted in only one case. Chromophobe RCC (1 case) was negative for p VHL. Exclusive cytoplasmic pVHL expression was more frequently noticed in low grade tumors. Conclusion: VHL protein expression and its cytoplasmic and nuclear distribution is of potential relevance for the diagnosis and biological behavior of RCCs. Combined nuclear and cytoplasmic expression of VHL protein is more frequently seen in low grade and early stage of renal cell carcinomas

Expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2/neu in surface epithelial ovarian tumors and its clinicohistopathological correlation

BACKGROUND: Ovarian cancers represent the 4th most frequent type of cancers among females and are the most common cause of death from gynecological cancers in the world. AIMS AND OBJECTIVES: The aim is to evaluate the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2/neu) immunohistochemical markers in surface epithelial ovarian tumors and its clinicopathological correlation with CA-125 level, histological type, grading of tumors, and prognosis of ovarian tumors. MATERIALS AND METHODS: This study included 48 cases of surface epithelial ovarian tumors including serous, mucinous, and adenocarcinoma Not Otherwise Specified (NOS). After grossing and processing, H and E sections were examined and representative 3–4 μm sections taken from blocks for immunohistochemistry which was performed with specific antibodies against ER, PR, and HER2/neu as per standard protocol. Statistical analysis was performed using Chi-square test. DISCUSSION AND RESULTS: ER expression was higher in malignant, borderline, serous tumors as compared to benign and mucinous tumors. PR expression was higher in borderline, serous tumors as compared to malignant and mucinous tumors. HER2/neu positive cases were higher in malignant, serous as compared to borderline and mucinous tumors. CONCLUSIONS: ER expression was found to be positive in most of serous tumors, have variable role in prognosis. PR expression showed protective role in survival of patients. Her2/neu was found to be expressed in higher grade and associated with poor prognosis. Together expression of ER and Her2/neu associated with decreased survival rates

Pilot study on quantifying the epithelial/mesenchymal hybrid state in the non-muscle invasive and muscle invasive bladder tumors: A promising marker of diagnosis and prognosis

Background: Manifestation of epithelial-to-mesenchymal transition (EMT) program in tumor cells is associated with the occurrence of multiple intermediate phenotypic states namely epithelial (E), mesenchymal (M) and hybrid E/M across the epithelial-mesenchymal spectrum and these states exhibit different invasive properties. Understanding the cellular and molecular mechanisms defining the E/M hybrid state of the cells during bladder tumor development may significantly aid in the identification of novel diagnostic and prognostic markers. Materials and methods: The present study is taken up to identify hybrid E/M score based on the immunohistochemical localization and surface expressions of epithelial proteins [E-cadherin and Beta-catenin] and mesenchymal marker proteins [N-cadherin and Vimentin] on formalin fixed paraffin embedded tumor sections of the prospective series of 99 non-muscle invasive bladder cancer (NMIBC) and 87 muscle invasive bladder cancer (MIBC) patients. E/M score was then statistically examined with patients’ demographics to assess its potential in the diagnosis and prognosis of UCB patients. Results: Among the E (E-cadherinhigh, β-cateninhigh), hybrid E/M (E-cadherinlow, β-cateninlow, N- cadherinhigh and Vimentinhigh) and M (N-cadherinhigh and Vimentinhigh) phenotypes, E/M phenotype was observed to be more prevalent in MIBC compared to E phenotype in NMIBC subtype. The current study reports the statistical association of tumor stage and tumor grade with the hybrid E/M state of urothelial tumor cells across both the subtypes. Hybrid E/M phenotype in MIBC patients was significantly shown to lower the overall survival time period compared to NMIBC patients. This supports the contribution of hybrid E/M state of tumor cells to the.aggressiveness of the disease. Conclusions: Characterizing the hybrid E/M state instead of all or none phenotype becomes an imperative to understand the dynamics of EMT and MET in the tumor pathophysiology of NMIBC and MIBC subtypes, and could contribute to better patient stratification and therapeutic strategies