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).RESULTS ERG 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.

Introduction C4d, an early product in the classical/lectin complement pathway has shown potential in the evaluation of C3 glomerulopathy where its absence would support an alternative pathway abnormality. As autoimmune/genetic complement testing is not readily available to most parts of the world, glomerular C4d staining may serve as a useful additional step toward the diagnosis. Methods To test this hypothesis, C4d staining was performed on a large cohort of C3 glomerulopathy. Archival cases from 2011 to 2017 were reviewed and immunohistochemistry for C4d was performed, scored (scale of 0 to 3+), and correlated with the immunofluorescence and ultrastructural findings. Paraffin immunofluorescence was performed in cases of “discordant C4d” to unmask Igs. Results Twenty-seven cases of dense deposit disease (DDD) and 14 cases of C3 glomerulonephritis (C3GN) were retrieved. C4d demonstrated a range of staining intensities with negative/traces in only 22% of DDD and 64% of C3GN. Lower-intensity C4d staining (1 to 2+) was mostly concordant with similar amounts of Igs/C1q. Discordant 3+ staining was noted in approximately 50% of cases of DDD and 20% of cases of C3GN. Among them, paraffin immunofluorescence unmasked polyclonal Igs in 2 of 5 cases of DDD and 1 of 3 cases of C3GN. Conclusion This observational study suggests that the presence of glomerular C4d should not exclude a C3 glomerulopathy. In lower intensities, it appears to represent overlying classical/lectin pathway activation with concordant Ig/C1q deposits. A subset of cases, however, displays intense and discordant C4d staining, which raises the possibility of an associated lectin pathway abnormality, a potential future area of study.

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