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Mod Pathol. 2017 Sep;30(9):1262-1272. doi: 10.1038/modpathol.2017.44. Epub 2017 Jun 16.

FOXA2 is a sensitive and specific marker for small cell neuroendocrine carcinoma of the prostate.

Author information

1
Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
2
Division of Hematology and Oncology, Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
3
Molecular Biology Institute, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
4
Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California-Los Angeles, Los Angeles, CA, USA.
5
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
6
Department of Pathology, Duke University School of Medicine, Durham, NC, USA.

Abstract

The median survival of patients with small cell neuroendocrine carcinoma is significantly shorter than that of patients with classic acinar-type adenocarcinoma. Small cell neuroendocrine carcinoma is traditionally diagnosed based on histologic features because expression of current immunohistochemical markers is inconsistent. This is a challenging diagnosis even for expert pathologists and particularly so for pathologists who do not specialize in prostate cancer. New biomarkers to aid in the diagnosis of small cell neuroendocrine carcinoma are therefore urgently needed. We discovered that FOXA2, a pioneer transcription factor, is frequently and specifically expressed in small cell neuroendocrine carcinoma compared with prostate adenocarcinoma from published mRNA-sequencing data of a wide range of human prostate cancers. We verified the expression of FOXA2 in human prostate cancer cell lines and xenografts, patient biopsy specimens, tissue microarrays of prostate cancers with lymph node metastasis, primary small cell neuroendocrine carcinoma, and metastatic treatment-related small cell neuroendocrine carcinoma and cases from a rapid autopsy program. FOXA2 expression was present in NCI-H660 and PC3 neuroendocrine cell lines, but not in LNCAP and CWR22 adenocarcinoma cell lines. Of the human prostate cancer specimens, 20 of 235 specimens (8.5%) showed diagnostic histologic features of small cell neuroendocrine carcinoma as judged histologically. Fifteen of 20 small cell neuroendocrine carcinoma tissues (75%) showed strong expression of FOXA2 (staining intensity 2 or 3). FOXA2 expression was also detected in 9 of 215 prostate cancer tissues (4.2%) that were histologically defined as adenocarcinoma. Our findings demonstrate that FOXA2 is a sensitive and specific molecular marker that may be extremely valuable in the pathologic diagnosis of small cell neuroendocrine carcinoma.

PMID:
28621319
DOI:
10.1038/modpathol.2017.44
[Indexed for MEDLINE]
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