Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma

Hsueh Li Tan, Akshay Sood, Hameed A. Rahimi, Wenle Wang, Nilesh Gupta, Jessica Hicks, Stacy Mosier, Christopher Gocke, Jonathan Ira Epstein, George J. Netto, Wennuan Liu, William B Isaacs, Angelo Michael Demarzo, Tamara Lotan

Research output: Contribution to journalArticle

Abstract

Purpose: Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide the diagnosis and therapy of this aggressive tumor. Experimental Design: We examined the status of RB1, TP53, and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy-number alteration analysis, and sequencing of formalin- fixed paraffin-embedded specimens. Results: We found retinoblastoma (Rb) protein loss in 90% of small cell carcinoma cases (26 of 29) with RB1 allelic loss in 85% of cases (11 of 13). Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3 of 7) showed Rb protein loss. In contrast, only 7% of primary high-grade acinar carcinomas (10 of 150), 11% of primary acinar carcinomas with neuroendocrine differentiation (4 of 35), and 15% of metastatic castrate-resistant acinar carcinomas (2 of 13) showed Rb protein loss. Loss of PTEN protein was seen in63% of small cell carcinomas (17 of 27), with38% (5 of 13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% of small cell carcinomas (14 of 25), with 60% of cases (6 of 10) showing TP53 mutation. Conclusions: Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by a validated IHC assay. As Rb protein loss rarely occurs in high-grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target.

Original languageEnglish (US)
Pages (from-to)890-903
Number of pages14
JournalClinical Cancer Research
Volume20
Issue number4
DOIs
StatePublished - 2014

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Neuroendocrine Carcinoma
Small Cell Carcinoma
Retinoblastoma
Retinoblastoma Protein
Acinar Cell Carcinoma
Loss of Heterozygosity
Immunohistochemistry
PTEN Phosphohydrolase
Neoplasms
Paraffin
Formaldehyde
Androgens
Prostate
Cell Differentiation
Prostatic Neoplasms
Research Design
Mutation
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma. / Tan, Hsueh Li; Sood, Akshay; Rahimi, Hameed A.; Wang, Wenle; Gupta, Nilesh; Hicks, Jessica; Mosier, Stacy; Gocke, Christopher; Epstein, Jonathan Ira; Netto, George J.; Liu, Wennuan; Isaacs, William B; Demarzo, Angelo Michael; Lotan, Tamara.

In: Clinical Cancer Research, Vol. 20, No. 4, 2014, p. 890-903.

Research output: Contribution to journalArticle

Tan, Hsueh Li ; Sood, Akshay ; Rahimi, Hameed A. ; Wang, Wenle ; Gupta, Nilesh ; Hicks, Jessica ; Mosier, Stacy ; Gocke, Christopher ; Epstein, Jonathan Ira ; Netto, George J. ; Liu, Wennuan ; Isaacs, William B ; Demarzo, Angelo Michael ; Lotan, Tamara. / Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma. In: Clinical Cancer Research. 2014 ; Vol. 20, No. 4. pp. 890-903.
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abstract = "Purpose: Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide the diagnosis and therapy of this aggressive tumor. Experimental Design: We examined the status of RB1, TP53, and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy-number alteration analysis, and sequencing of formalin- fixed paraffin-embedded specimens. Results: We found retinoblastoma (Rb) protein loss in 90{\%} of small cell carcinoma cases (26 of 29) with RB1 allelic loss in 85{\%} of cases (11 of 13). Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43{\%} (3 of 7) showed Rb protein loss. In contrast, only 7{\%} of primary high-grade acinar carcinomas (10 of 150), 11{\%} of primary acinar carcinomas with neuroendocrine differentiation (4 of 35), and 15{\%} of metastatic castrate-resistant acinar carcinomas (2 of 13) showed Rb protein loss. Loss of PTEN protein was seen in63{\%} of small cell carcinomas (17 of 27), with38{\%} (5 of 13) showing allelic loss. By IHC, accumulation of p53 was observed in 56{\%} of small cell carcinomas (14 of 25), with 60{\%} of cases (6 of 10) showing TP53 mutation. Conclusions: Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by a validated IHC assay. As Rb protein loss rarely occurs in high-grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target.",
author = "Tan, {Hsueh Li} and Akshay Sood and Rahimi, {Hameed A.} and Wenle Wang and Nilesh Gupta and Jessica Hicks and Stacy Mosier and Christopher Gocke and Epstein, {Jonathan Ira} and Netto, {George J.} and Wennuan Liu and Isaacs, {William B} and Demarzo, {Angelo Michael} and Tamara Lotan",
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T1 - Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma

AU - Tan, Hsueh Li

AU - Sood, Akshay

AU - Rahimi, Hameed A.

AU - Wang, Wenle

AU - Gupta, Nilesh

AU - Hicks, Jessica

AU - Mosier, Stacy

AU - Gocke, Christopher

AU - Epstein, Jonathan Ira

AU - Netto, George J.

AU - Liu, Wennuan

AU - Isaacs, William B

AU - Demarzo, Angelo Michael

AU - Lotan, Tamara

PY - 2014

Y1 - 2014

N2 - Purpose: Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide the diagnosis and therapy of this aggressive tumor. Experimental Design: We examined the status of RB1, TP53, and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy-number alteration analysis, and sequencing of formalin- fixed paraffin-embedded specimens. Results: We found retinoblastoma (Rb) protein loss in 90% of small cell carcinoma cases (26 of 29) with RB1 allelic loss in 85% of cases (11 of 13). Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3 of 7) showed Rb protein loss. In contrast, only 7% of primary high-grade acinar carcinomas (10 of 150), 11% of primary acinar carcinomas with neuroendocrine differentiation (4 of 35), and 15% of metastatic castrate-resistant acinar carcinomas (2 of 13) showed Rb protein loss. Loss of PTEN protein was seen in63% of small cell carcinomas (17 of 27), with38% (5 of 13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% of small cell carcinomas (14 of 25), with 60% of cases (6 of 10) showing TP53 mutation. Conclusions: Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by a validated IHC assay. As Rb protein loss rarely occurs in high-grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target.

AB - Purpose: Small cell neuroendocrine carcinoma of the prostate is likely to become increasingly common with recent advances in pharmacologic androgen suppression. Thus, developing molecular markers of small cell differentiation in prostate cancer will be important to guide the diagnosis and therapy of this aggressive tumor. Experimental Design: We examined the status of RB1, TP53, and PTEN in prostatic small cell and acinar carcinomas via immunohistochemistry (IHC), copy-number alteration analysis, and sequencing of formalin- fixed paraffin-embedded specimens. Results: We found retinoblastoma (Rb) protein loss in 90% of small cell carcinoma cases (26 of 29) with RB1 allelic loss in 85% of cases (11 of 13). Of acinar tumors occurring concurrently with prostatic small cell carcinoma, 43% (3 of 7) showed Rb protein loss. In contrast, only 7% of primary high-grade acinar carcinomas (10 of 150), 11% of primary acinar carcinomas with neuroendocrine differentiation (4 of 35), and 15% of metastatic castrate-resistant acinar carcinomas (2 of 13) showed Rb protein loss. Loss of PTEN protein was seen in63% of small cell carcinomas (17 of 27), with38% (5 of 13) showing allelic loss. By IHC, accumulation of p53 was observed in 56% of small cell carcinomas (14 of 25), with 60% of cases (6 of 10) showing TP53 mutation. Conclusions: Loss of RB1 by deletion is a common event in prostatic small cell carcinoma and can be detected by a validated IHC assay. As Rb protein loss rarely occurs in high-grade acinar tumors, these data suggest that Rb loss is a critical event in the development of small cell carcinomas and may be a useful diagnostic and potential therapeutic target.

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