Small cell carcinoma of the endometrium: report of a case with analysis of Wnt/beta-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. Beta-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 beta-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 beta-catenin accumulation in neuroendocrine tumors arising in different organs, suggesting a role for the Wnt/beta-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 beta-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 beta-catenin gene or exon 15 of the APC gene in the present case. Although the mechanism of nuclear accumulation of beta-catenin is still unknown, the heterotopic nuclear localization of beta-catenin may play a role in the tumor invasion process and, subsequently, may be associated with the aggressive behavior of SCCE.
Meirmanov
Serik
S
Department of Molecular Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Nakashima
Masahiro
M
Rogounovitch
Tatiana
T
Fukuda
Eiichiro
E
Nakayama
Toshiyuki
T
Sato
Futaba
F
Sekine
Ichiro
I
D014408:Biomarkers, Tumor / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000378:metabolism* / Q000556:secondary / Q000601:surgery; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D019938:Cyclin D1