Study of signaling routes in adenocarcinoma in situ and adenocarcinoma of endocervix

Wnt/β-catenin and EGFR/PI3K/AKT are signaling pathways frequently activated in cancer. The first is related to epithelial-mesenchymal transition (EMT) phenomena and the second to the processes of cell proliferation, invasion, and mobility. Cervical adenocarcinoma and its possible precursor, adenocarcinoma in situ (AIS), are aggressive tumors that are difficult to diagnose early. For these reasons, the activity of the aforementioned pathways was investigated in relation to the mechanisms of invasion of cervical adenocarcinomas. High-risk human papillomavirus-related adenocarcinomas (HPVA) were selected from surgical materials and biopsies from the archive of the Hospital de Clínicas de C.A.B.A., Argentina. To select HPVA, HPV typing was performed using polymerase chain reaction. The two signaling pathways were analyzed by immunohistochemistry, using antibodies against vimentin, alpha-smooth muscle actin (αSMA), β-catenin, EGFR, PI3K, and AKT. EMT markers (αSMA and vimentin) were negative in adenocarcinomas; vimentin was expressed in 13/55 of the AIS. Components of the ERGR/PI3K/AKT pathway were expressed in adenocarcinomas (EGFR: 70%, PI3K 47%, AKT 67%) and AIS (EGFR: 33%, PI3K 51%, AKT 54%). In total, 47% of adenocarcinomas and 32% of AIS showed full activation of the EGFR/PI3K/AKT pathway. The action of HR-HPVE6 destabilizing intercellular junctions and the activation of AKT would explain the mobility and invasiveness of cervical adenocarcinoma cells, independently of the EMT phenomenon.