Exploratory cross-sectional study to evaluate the metalloproteinases role as ‘immunoscore’ for HPV-induced cervical lesions

Abstract

Abstract Cervical cancer (CC) is the fourth most common type of cancer among women and is responsible for about 8% of female cancer deaths worldwide. Understanding how the tumor microenvironment behaves is essential to realize the carcinogenic process, and thus infer possible prognostic biomarkers in the CC development. One of the prognostic factors that has aroused interest in recent years is the increased expression of metalloproteinases (MMPs) in tumor tissues, which is associated with tumor growth and metastasis, and recurrence of degradation of extracellular matrix (ECM) components in tissues of different tumors. Thus, our objective is to evaluate the in situ distribution of MMPs+ cells (MMP-2, -7, -9), as well as TIMP-2+, EphA2+ and EfrinA1+ cells in intraepithelial (IE) and marginal stroma (MS) areas using the technique of immunohistochemistry and immunoscore analysis in low- and high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively) and CC. We observed in MS, a high distribution of MMPs+ (-2, -7 and − 9), TIMP2+ and EPHA2+ cells in the HSIL and CC group compared to the control. Regarding IE, we observed this same pattern, except in EPHA2 where there was a decrease in the positive cells distribution in CC compared to control and LSIL. Regarding the “immunoscore”, from 15 possible profiles, we found statistical differences in only 9 (MMP-2+/MMP-9+, MMP-2+/EphA2+, MMP-7+/MMP-9+, MMP- 7+/TIMP-2+, MMP-7+/EphA2+, MMP-9+/EphA2+, TIMP-2+/EphA2+, TIMP-2+/EphrA1+ and EphA2+/EphrA1+) when the groups were compared. However, only the MMP-7+/MMP-9+ profile can be used as a prognostic factor for the development of CC and the MMP-7+/EphA2+, MMP-9+/EphA2+ and TIMP-2+/EphA2+ profiles may be related to the development of precancerous lesions. A more comprehensive review of longitudinal studies should be performed to link these “immunoscores” to CC progression and validate their value as a prognostic method.