Small Cell Carcinoma of the Endometrium: Report of a Case with Analysis of Wnt/β-Catenin Pathway

Small cell carcinoma of the endometrium (SCCE) is extremely rare. Previous reports indicate that SCCE frequently shows systemic spread and has a poor prognosis. β-catenin has been shown to be a key downstream effector of the Wnt signaling pathway, which regulates cell growth and survival. Decreased membranous expression of β-catenin in cancers correlates with poor prognosis and is associated with dissemination of tumor cells and the formation of metastases. Recently, some different investigators demonstrated aberrant β-catenin accumulation in neuroendocrine tumors arising in different organs, suggesting a role for the Wnt/β-catenin signaling pathway during neuroendocrine tumorigenesis. Here, we report a new case of SCCE associated with peritoneal spreading and aggressive course; the patient died one month after surgery. This study also aimed at assessing the involvement of the Wnt signaling pathway in this rare neuroendocrine tumor. Interestingly, both intense nuclear β-catenin accumulation and cyclin D1 immunoreactivity were restricted to carcinoma cells invading lymphatic vessels. However, mutation analysis failed to demonstrate any mutation in exon 3 of the β-catenin gene or exon 15 of the APC gene in the present case. Although the mechanism of nuclear accumulation of β-catenin is still unknown, the heterotopic nuclear localization of β-catenin may play a role in the tumor invasion process and, subsequently, may be associated with the aggressive behavior of SCCE.