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

Publication ,  Journal Article
Park, JW; Lee, JK; Witte, ON; Huang, J
Published in: Mod Pathol
September 2017

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.

Duke Scholars

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Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

September 2017

Volume

30

Issue

9

Start / End Page

1262 / 1272

Location

United States

Related Subject Headings

  • Tumor Burden
  • Tissue Array Analysis
  • Prostatic Neoplasms
  • Predictive Value of Tests
  • Pathology
  • Neoplasm Transplantation
  • Mice, Inbred NOD
  • Male
  • Immunohistochemistry
  • Humans
 

Citation

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Park, J. W., Lee, J. K., Witte, O. N., & Huang, J. (2017). FOXA2 is a sensitive and specific marker for small cell neuroendocrine carcinoma of the prostate. Mod Pathol, 30(9), 1262–1272. https://doi.org/10.1038/modpathol.2017.44
Park, Jung Wook, John K. Lee, Owen N. Witte, and Jiaoti Huang. “FOXA2 is a sensitive and specific marker for small cell neuroendocrine carcinoma of the prostate.Mod Pathol 30, no. 9 (September 2017): 1262–72. https://doi.org/10.1038/modpathol.2017.44.
Park JW, Lee JK, Witte ON, Huang J. FOXA2 is a sensitive and specific marker for small cell neuroendocrine carcinoma of the prostate. Mod Pathol. 2017 Sep;30(9):1262–72.
Park, Jung Wook, et al. “FOXA2 is a sensitive and specific marker for small cell neuroendocrine carcinoma of the prostate.Mod Pathol, vol. 30, no. 9, Sept. 2017, pp. 1262–72. Pubmed, doi:10.1038/modpathol.2017.44.
Park JW, Lee JK, Witte ON, Huang J. FOXA2 is a sensitive and specific marker for small cell neuroendocrine carcinoma of the prostate. Mod Pathol. 2017 Sep;30(9):1262–1272.

Published In

Mod Pathol

DOI

EISSN

1530-0285

Publication Date

September 2017

Volume

30

Issue

9

Start / End Page

1262 / 1272

Location

United States

Related Subject Headings

  • Tumor Burden
  • Tissue Array Analysis
  • Prostatic Neoplasms
  • Predictive Value of Tests
  • Pathology
  • Neoplasm Transplantation
  • Mice, Inbred NOD
  • Male
  • Immunohistochemistry
  • Humans