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.
Highlights
Cervical intraepithelial neoplasia grade 3 (CIN 3) is the precancerous lesion that may progress to invasive carcinoma [1,2]
The MMP-14, MMP-2 and TIMP-1 proteins were markedly expressed in tumor cells and stromal cells most cases
The mean percentage ranged from 80.2% (Group 2 - invasive carcinoma) to 89.1% (Group 2 – CIN 3); for stromal cells, the mean percentage ranged from 51.9% (Group 1 - CIN 3) to 66.1% (Group 3 – invasive carcinoma)
Summary
Cervical intraepithelial neoplasia grade 3 (CIN 3) is the precancerous lesion that may progress to invasive carcinoma [1,2]. Transformation from preinvasive neoplasia to invasive carcinoma starts by a focal disruption of the subepithelial basement membrane. Potent proteolytic enzymes termed matrix proteinases (MMPs) are known to play a key role in this process [3]. MMP-2 and MMP-9 are proteolytic enzymes with a major role in type IV collagen digestion, an important event in vascular invasion and metastasis. MMP-14 is a key enzyme in tumor cell invasion. This enzyme seems to be implicated in both breaching the basement membrane by tumor cells and cell invasion through interstitial type-I collagen tissues [6]
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