Expression of MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2 in Intraepithelial and Invasive Cervical Neoplasia

Abstract

Aim: To evaluate the expression of MMP-2, MMP-9, MMP-14, TIMP-1 and TIMP-2 in Cervical intraepithelial neoplasia grade 3 (CIN 3) and invasive squamous cell carcinoma. Methods and Results:This study comprised three groups: Group 1: 55 cases with CIN 3; Group 2: 30 cases with CIN 3 and invasive carcinoma components; Group 3: 46 cases with invasive carcinoma. Protein expression was investigated in tumor and stromal cells by immunohistochemistry and percentages of immunostained cells were determined. The mean percentage of MMP-14 tumor cells was significantly higher in stromal cells in all groups. TIMP-2 and MMP-9 expression was significantly higher in stromal cells than in tumor cells. TIMP-1 had a significantly higher expression in stromal cells of carcinoma and tumor cells of CIN 3. Stromal cells expression of MMP-2, MMP-14, TIMP-1 was increased with the severity of cervical neoplasia. The expression of MMP-2 in stromal cells that was higher in CIN 3 component of Group 2 than in CIN 3 of Group 1. Conclusions:The increase in MMP-2 expression from CIN 3 to invasive cervical cancer reinforces their role in cervical cancer progression. From CIN 3 to invasive cervical carcinoma, TIMP-1 expression increased in stromal cells and decreased in tumor cells.

Tumoral and stromal expression of MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2, and VEGF-A in cervical cancer patient survival: a competing risk analysis

“…The immunohistochemical analyses for MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2, and VEGF-A were performed as described previously by Westin et al through hot spots areas [25,26]. Total cells and immunostained cells (stromal and tumor cells separately) were counted by two observers using morphometric software (Image-Pro Plus®, version 6.3, Olympus).…”

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

“…Our results showed an increase in MMP-9 + cells dispersion in HSIL and CC groups compared to control group, mainly in MS area, reinforcing the idea that together with MMP-2 and MMP-7, the adjacent tissue is preparing for tumor invasion. A study conducted by Westin et al (2015) demonstrated an increase of MMP-9 expression in stromal cells in all of groups (CIN I, CIN II and CIN III) compared to control group, suggesting that MMP-9 is related to interaction between the tumor and stromal cells. Corroborating with our results, Matheus et al (2014) reported an increase in MMP-9 + cells distribution in normal cells adjacent to dyskaryotic cells in cervical smear samples as lesion progressed, suggesting an induction of MMP-9 production by neighboring the tumor cells and the importance of cell-cell interaction during carcinogenesis.…”