Telomere lengths differ significantly between small-cell neuroendocrine prostate carcinoma and adenocarcinoma of the prostate

Christopher M Heaphy, Michael Haffner, Mindy K. Graham, David Lim, Christine Davis, Eva Corey, Jonathan I. Epstein, Mario A. Eisenberger, Hao Wang, Angelo M. De Marzo, Alan Keith Meeker, Tamara Lotan

Research output: Contribution to journalArticle

Abstract

Small-cell neuroendocrine carcinoma (SCNC) of the prostate is an aggressive subtype with frequent TP53 mutation and RB1 inactivation; however, the molecular phenotype remains an area of investigation. Here, we compared telomere lengths in prostatic SCNC and usual-type prostatic adenocarcinoma (AdCa). We studied 32 cases of prostatic SCNC (including 11 cases with concurrent AdCa) and 347 cases of usual-type AdCa on tissue microarrays. Telomere lengths in tumor cells were qualitatively compared with those in normal cells using a telomere-specific fluorescence in situ hybridization assay. ERG, PTEN, and TP53 status were assessed in a proportion of cases using genetically validated immunohistochemistry protocols. Clinicopathological and molecular characteristics of cases were compared between the telomere groups using the chi-square test.A significantly higher proportion of prostatic SCNC cases (50%, 16/32) showed normal/long telomeres compared with AdCa cases (11%, 39/347; P < 0.0001). In 82% (9/11) of cases with concurrent SCNC and AdCa, the paired components were concordant for telomere length status. Among AdCa cases, the proportion of cases with normal/long telomeres significantly increased with increasing tumor grade group (P = 0.01) and pathologic stage (P = 0.02). Cases with normal/long telomeres were more likely to be ERG positive (P = 0.04) and to have TP53 missense mutation (P = 0.01) than cases with short telomeres.Normal or long telomere lengths are significantly more common in prostatic SCNC than in AdCa and are similar between concurrent SCNC and AdCa tumors, supporting a common origin. Among AdCa cases, longer telomere lengths are significantly associated with high-risk pathologic and molecular features.

Original languageEnglish (US)
Pages (from-to)70-79
Number of pages10
JournalHuman pathology
Volume101
DOIs
StatePublished - Jul 2020

Keywords

  • Adenocarcinoma
  • Neuroendocrine
  • Prostate cancer
  • Small-cell carcinoma
  • Telomeres

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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