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Interactions and relationships of PTEN , ERG , SPINK1 and AR in castration‐resistant prostate cancer
Author(s) -
Bismar Tarek A,
Yoshimoto Maisa,
Duan Qiuli,
Liu Shuhong,
Sircar Kanishka,
Squire Jeremy A
Publication year - 2012
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2011.04116.x
Subject(s) - pten , erg , tensin , prostate cancer , tmprss2 , biology , androgen receptor , cancer research , immunohistochemistry , prostate , cancer , microbiology and biotechnology , pathology , medicine , genetics , pi3k/akt/mtor pathway , immunology , apoptosis , retina , disease , covid-19 , neuroscience , infectious disease (medical specialty)
Bismar T A, Yoshimoto M, Duan Q, Liu S, Sircar K & Squire J A
(2012) Histopathology 60, 645–652
Interactions and relationships of PTEN , ERG , SPINK1 and AR in castration‐resistant prostate cancer Aims: Recently, ETS‐related gene ( ERG ) gene rearrangements, phosphatase tensin homologue ( PTEN ) deletions and serine protease inhibitor Kazal type 1 (SPINK1) overexpression were investigated as potential markers for molecularly subtyping prostate cancer (PCA). However, their incidence and co‐association in castration‐resistant PCA (CRPC) has not been characterized fully. Methods and results: A cohort of 59 CRPC patients was investigated for ERG rearrangements, PTEN deletions and androgen receptor ( AR ) amplification by fluorescence in‐situ hybridization. SPINK1 overexpression was assessed by immunohistochemistry. ERG rearrangements and PTEN deletions were detected in 22 of 53 (41.5%) and 35 of 55 (63.6%) of cases, with 15 of 22 (68.1%) of ERG rearrangements occurring through deletions. SPINK1 overexpression occurred in three of 51 (5.8%) of cases exclusively in non‐ ERG rearranged and AR amplification was detected in 12 of 49 (24.4%) of cases. Only PTEN deletions showed intrafocal heterogeneity occurring in nine of 35 (25.7%) of cases. PTEN deletions were significantly associated with each of ERG rearrangements occurring by deletions only ( P = 0.001), AR amplification ( P = 0.002) and SPINK1 overexpression ( P = 0.002). None of the SPINK1 overexpressing tumours showed AR amplification ( P = 0.005) and all occurred in PTEN deleted foci ( P = 0.002). Conclusion: The study supports the heterogeneous nature of CRPC and confirms a significant association between PTEN, ERG, AR and SPINK1. Characterizing combined markers will aid in defining PCA subgroups relevant to prognosis contributing to the design of improved therapeutic approaches for CRPC.