American Association for Cancer Research
10780432ccr150744-sup-147385_1_supp_3049194_nr4vlr.png (132.89 kB)

Supplementary Figure S1 from Cyclin D1 Loss Distinguishes Prostatic Small-Cell Carcinoma from Most Prostatic Adenocarcinomas

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posted on 2023-03-31, 19:04 authored by Harrison Tsai, Carlos L. Morais, Mohammed Alshalalfa, Hsueh-Li Tan, Zaid Haddad, Jessica Hicks, Nilesh Gupta, Jonathan I. Epstein, George J. Netto, William B. Isaacs, Jun Luo, Rohit Mehra, Robert L. Vessella, R. Jeffrey Karnes, Edward M. Schaeffer, Elai Davicioni, Angelo M. De Marzo, Tamara L. Lotan

Supplementary Figure S1: The ratio of CDKN2A/CCND1 reflects Rb functional and genetic status and distinguishes small cell carcinoma from prostatic adenocarcinoma in publicly available data from patient derived xenografts (PDX).



Purpose: Small-cell neuroendocrine differentiation in prostatic carcinoma is an increasingly common resistance mechanism to potent androgen deprivation therapy (ADT), but can be difficult to identify morphologically. We investigated whether cyclin D1 and p16 expression can inform on Rb functional status and distinguish small-cell carcinoma from adenocarcinoma.Experimental Design: We used gene expression data and immunohistochemistry to examine cyclin D1 and p16 levels in patient-derived xenografts (PDX), and prostatic small-cell carcinoma and adenocarcinoma specimens.Results: Using PDX, we show proof-of-concept that a high ratio of p16 to cyclin D1 gene expression reflects underlying Rb functional loss and distinguishes morphologically identified small-cell carcinoma from prostatic adenocarcinoma in patient specimens (n = 13 and 9, respectively). At the protein level, cyclin D1, but not p16, was useful to distinguish small-cell carcinoma from adenocarcinoma. Overall, 88% (36/41) of small-cell carcinomas showed cyclin D1 loss by immunostaining compared with 2% (2/94) of Gleason score 7–10 primary adenocarcinomas at radical prostatectomy, 9% (4/44) of Gleason score 9–10 primary adenocarcinomas at needle biopsy, and 7% (8/115) of individual metastases from 39 patients at autopsy. Though rare adenocarcinomas showed cyclin D1 loss, many of these were associated with clinical features of small-cell carcinoma, and in a cohort of men treated with adjuvant ADT who developed metastasis, lower cyclin D1 gene expression was associated with more rapid onset of metastasis and death.Conclusions: Cyclin D1 loss identifies prostate tumors with small-cell differentiation and may identify a small subset of adenocarcinomas with poor prognosis. Clin Cancer Res; 21(24); 5619–29. ©2015 AACR.

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