Rb loss is characteristic of prostatic small cell neuroendocrine carcinoma
Hsueh-Li Tan1, Akshay Sood, Hameed A Rahimi
1Authors' Affiliations: Pathology, Department of Pathology, Henry Ford Health System, Detroit, Michigan; Oncology, and Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland; and Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina.
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 in 63% of small cell carcinomas (17 of 27), with 38% (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.
Insights
Loss of retinoblastoma (Rb) protein is common in small cell prostate cancer, unlike in acinar tumors. Rb protein loss may be a key event and a target for treating this aggressive cancer.
Area of Science:
- Oncology
- Molecular Pathology
Background:
- Small cell neuroendocrine carcinoma of the prostate is an aggressive tumor type.
- Its incidence may increase with advanced androgen suppression therapies.
- Identifying molecular markers is crucial for diagnosis and treatment.
Purpose of the Study:
- To investigate the status of RB1, TP53, and PTEN in prostatic small cell and acinar carcinomas.
- To determine if RB1 alterations can serve as a diagnostic marker for small cell prostate cancer.
Main Methods:
- Immunohistochemistry (IHC) was used to examine protein expression.
- Copy-number alteration analysis and sequencing were performed on tumor specimens.
- The study analyzed formalin-fixed paraffin-embedded samples.
Main Results:
- Retinoblastoma (Rb) protein loss occurred in 90% of small cell prostate cancer cases.
- RB1 allelic loss was found in 85% of small cell carcinoma cases.
- Rb protein loss was significantly less frequent in acinar carcinomas (7-15%).
Conclusions:
- Loss of RB1 via deletion is a frequent event in small cell prostate cancer.
- This loss can be reliably detected using a validated IHC assay.
- Rb protein loss is a potential diagnostic and therapeutic target for small cell prostate cancer.
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