Intracellular pathways in infiltrating squamous cell carcinoma of the cervix. Identification of new prognostic markers

Background: Tyrosine-kinase receptors are frequently activated in malignant human tumours. This activation results in high levels of proliferation, migration, dedifferentiation, dissemination and resistance to apoptosis of the tumour cells. Alterations in the following signalling pathways related to ErbB/HER: RAS-RAF-ERK, PIK3-AKT, MAPK, and NFKB have been described. Studying these signaling pathways could help identify more aggressive tumours and thus provide information about potential changes in therapy. Material and methods: We performed an immunohistochemical study of EGFR, p-EGFR, p38, p-ERK. 1/2, JNK, p-AKT, p65, p50, p52, relB, c-Rel and MAPK-1 in 32 infiltrating squamous cell carcinomas of the uterine cervix using a tissue array. Results: Only p-ERK immunoexpression correlated with the stage of the disease (. P<. .001) and the relapse (. P<. .001). Furthermore, the MKP1 immunoexpression inversely correlated with the immunoexpression of p-JNK (. P= .036) and p-p38 (. P= .011) levels, thereby indicating that MKP1 could exert anti-apoptotic activity. This hypothesis has been further reinforced by the recently reported correlation between MKP detection and poor response to treatment (chemo- and radiotherapy). Conclusions: Our observations indicate that more aggressive tumours show higher p-ERK and MKP1 immunoexpression and lower levels of p-JNK and p-p38 immunoexpression, the latter two favour tumour resistance to chemotherapy. p-ERK and MKP1 immunoexpression could serve as prognostic factors and therapeutic targets for these tumours. © 2013 SEAP y SEC.