DLG1 protein expression in squamous intraepithelial cervical lesions and its relevance to disease outcome

ANA L. CAVATORTA; DI GREGORIO, A; CABRAL M; BUGNON VALDANO MARINA; MARZIALI FEDERICO; CITTADINI J; NOCITO ANA LIA; GARDIOL DANIELA

Workshop; First ICGEB Workshop "Human Papillomavirus:From Basic Biology to Cervical Cancer Prevention?; 2014

Cervical cancer is one of the most common cancer affecting women worldwide. The human papilloma virus (HPV) infection is a well thought-out necessary intermediary step in the development of cervical cancer, in which this virus is present in more than 99% of cases. However, not all HPV infections give rise to cervical dysplasia and promote its development to carcinoma. Most of the low grade squamous intraepithelial lesions (LSIL) regress spontaneously and only some will progress to high grade squamous intraepithelial lesions (HSIL) and cervical squamous cell carcinomas (SCC). Therefore, it is necessary to identify some markers to offer information concerning the HPV infection status and the progression risk. The aim of our study consist in evaluate if changes in the expression level of DLG1 oncosuppressor, target of the viral HPV E6 oncoprotein, which is involved in the control of cell proliferation and polarity, may be used as histological biomarker. In previous studies we evaluated the contribution of HPV E6 activity in the progression to malignancy by analyzing DLG1 expression in HPV-associated lesions by immunohistochemestry (IHC). The results showed that for LSIL specimens there are two archetypes according to the different DLG1 immunostaining patterns. One comprises samples where DLG1 expression and distribution, were quite similar to those observed in normal epithelium. The other subset of LSIL biopsies presented an over expression of DLG1 staining similar to those observed for the HSIL immunostaining archetype. Therefore, given the characteristics of DLG1 and its likely involvement in both tumor suppressor and oncogenic processes, it is interesting to know whether these different patterns of expression may be associated with progression and/or regression of LSIL differential injury. We are analyzing cervical biopsies from women, in whom diagnoses of LSIL are made, by IHC using antibody against DLG1 protein. The results will be related to the diagnosis and monitoring of patients during the 24-month follow-up. Our preliminary results suggest that LSIL specimens showing a DLG1 staining pattern similar to that of normal tissue are significantly more likely to regress as compared to those expressing a diffuse and very intense DLG1, archetype that responds to that we have previously observed for HSIL specimens. However, a large number of samples should be analyzed in order to determine if the detection of DLG1 pattern expression could present prognostic information about the evolution of early dysplastic cervical lesions and can be useful in predicting their biologic potential