@article{oai:repo.qst.go.jp:00046042, author = {Imadome, Kaori and Iwakawa, Mayumi and Nakawatari, Miyako and Fujita, Hidetoshi and Kato, Shingo and Ohno, Tatsuya and Nakamura, Etsuko and Ohkubo, Yu and Tamaki, Tomoaki and Kiyohara, Hiroki and Imai, Takashi and 今留 香織 and 岩川 眞由美 and 中渡 美也子 and 藤田 英俊 and 加藤 眞吾 and 大野 達也 and 中村 悦子 and 大久保 悠 and 田巻 倫明 and 清原 浩樹 and 今井 高志}, issue = {10}, journal = {Cancer Biology & Therapy}, month = {Nov}, note = {Adenosquamous carcinoma (ASC) is a relatively uncommon histological subtype of cervical cancer (CC). A point of controversy is the relative prognosis of ASC compared to squamous cell carcinoma (SCC). We hypothesized that ASC could be classified into two intrinsic molecular subtypes with different outcomes. We examined 143 biopsy samples of CC patients to identify a molecule for classification using microarray expression analysis and immunohistochemical analysis (IHA). We found specific expression profiles of candidate genes that distinguished two clusters. All adenocarcinoma (AC) patients were classified into one cluster, and most SCC patients fell into the other cluster. ASC patients were classified across the two clusters, which showed significantly different prognoses. The SCC-like expression signature comprised ANXA8, CK5, IFI16, and nectin-1; and the AC-like signature comprised EpCAM, and TMEM98. These signature-specific genes hypothetically indicated specific pathways by ontological analysis. The AC-like signature suggested an epithelial-mesenchymal transition and activated beta-catenin pathway, while the SCC-like signature suggested keratinocyte differentiation, HPV infection, and p53-mediated apoptosis. IHA revealed that positive expression of the most promising protein, EpCAM, was significantly associated with poor prognosis. In addition, the inhibition of EpCAM expression using siRNA significantly increased radiation-induced cell death in the cervical cell line, ME-180. In conclusion, we identified two possible ASC subtypes associated with different expression profiles and different prognoses. This work provides a novel set of genes that could be used as independent prognostic markers and therapy targets.}, pages = {1019--1026}, title = {Subtypes of Cervical Adenosquamous Carcinomas Classified by EpCAM expression Related to Radiosensitivity}, volume = {10}, year = {2010} }