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

CAVATORTA AL; DI GREGORIO, MA; CABRAL, M; BUGNON VALDANO, M; MARZIALI, F; CITTADINI, J; NOCITO, AL; GARDIOL, D

Trieste

Congreso; ICGEB DNA Tumour Virus Meeting 2015; 2015

ICGEB

Annually, an estimated 530,000 new episodes of cervical cancer are diagnosed worldwide, of which more than 85% occur in developing countries, with a mortality approaching 50%. The main clinical stages in cervical carcinogenesis include HPV infection, persistence, progression to precancerous lesions and invasion. Invasive cervical cancer is preceded by a progressive spectrum of cervical epithelial abnormalities. However, not all HPV infections give rise to cervical dysplasia and promote its development to carcinoma. It is well known that most of the LSIL (low-grade squamous intraepithelial lesions) are transient and regress spontaneously to normal epithelium in 1-2 years. Nevertheless, 10% to 15% of these LSIL progress to HSIL (high-grade squamous intraepithelial lesions), which are considered the immediate precursors to cervical carcinoma. Therefore, it is necessary to identify some markers to offer information concerning the HPV infection status and the progression risk. Our study consisted in evaluating if changes in the expression of DLG1 oncosuppressor, may be used as a histological biomarker. In previous studies we analyzed the pattern of DLG1 expression in the progression to malignancy in HPV-associated lesions by immunohistochemistry (IHC). The results showed for LSIL specimens, two archetypes according to the different DLG1 patterns. One comprised samples where DLG1 expression was quite similar to that observed in normal epithelium. The other subset of LSIL biopsies presented an over expression of DLG1 staining similar to that obtained for the HSIL samples. Therefore, given the characteristics of DLG1 and its likely involvement in both tumor suppression and oncogenic processes, it is interesting to know whether these different patterns of expression may be associated with progression and/or regression of the LSIL. We analyzed 30 cervical biopsies from women with LSIL diagnosis, for DLG1 expression by IHC. These results were correlated with the clinical monitoring of the patients during the follow-up period. In our pilot study, DLG1 staining demonstrated to be an excellent test that would help in selecting patients who require a less intensive follow-up and those with a higher risk to progress. Specifically, patients with LSIL biopsies that presented an immunostaining pattern similar to those observed for normal tissue rarely progress. However, further studies including a larger number of samples are encouraged to validate this potential biomarker.