Shared TP53 gene mutation in morphologically and phenotypically distinct concurrent primary small cell neuroendocrine...

Small cell carcinoma of the prostate is an uncommon neoplasm, the origin of which has been controversial. To address this, we performed transcriptome profiling and TP53 sequencing of concurrent small cell and prostatic adenocarcinoma to determine the relationship between these entities.

We identified an unusual case of primary prostate cancer that contained adjacent acinar adenocarcinoma (Gleason score 4 + 3 = 7) and small cell carcinoma. We performed laser capture microdissection to isolate tumor components and performed gene expression and TP53 gene sequence analysis on each component, with results validated by immunohistochemistry for PSA, PSAP, PSMA, androgen receptor, NKX 3.1 and neuroendocrine markers.

Transcriptome profiling of the carcinoma components identified 99 genes with a greater than 10-fold differential expression between prostatic adenocarcinoma and small cell carcinoma, many of which have not been previously reported in prostate cancer. The small cell carcinoma component demonstrated upregulation of proliferative and neuroendocrine markers and tyrosine kinase receptors, and downregulation of cell adhesion molecules, supporting the aggressive nature of this form of carcinoma. Sequencing of the TP53 gene suggested a common clonal origin for both components.

This is the first report of a primary small cell carcinoma of the prostate subjected to extensive molecular analysis and the first to show a clonal relation between two morphologically distinct prostate cancer types. The evidence of progression to small cell carcinoma may yield important insights into the pathogenesis of this entity and provide a novel spectrum of molecular markers to further dissect cellular pathways important in tumor progression.