Obstetrics and Gynecology: Gynecology
Comparative study of MMP-2 (matrix metalloproteinase 2) immune expression in normal uterine cervix, intraepithelial neoplasias, and squamous cells cervical carcinoma☆

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Abstract

Objective

This study was undertaken to evaluate the levels of matrix metalloproteinase 2 (MMP-2) in the precursors lesions and in the invasive cervical carcinoma and to quantify the immune reactive expression of MMP-2, using MMP-2 immunohistochemistry, in intraepithelial cervical neoplasias and in the invading cervical carcinoma.

Study design

We evaluated 60 samples of cervical tissues using immunohistochemistry for MMP-2 in 5 distinct groups. The groups were divided in control, cervical intraepithelial neoplasia I (CIN I), CIN II, CIN III, and cervical invading carcinoma.

Results

MMP-2 expression was found gradually increased according to the degree of cervical intraepithelial neoplasia and cervical carcinoma. (Control<CIN I<CIN II<CIN III<Carcinoma)

Conclusion

Our results suggest that the expression of MMP-2 can distinguish CIN I, II, and III grades and the invading carcinoma.

Section snippets

Material and methods

A total of 60 paraffin-embedded samples obtained from patients treated at the Gynecology Department were selected from the Pathology archives both from the Federal University of São Paulo–Escola Paulista de Medicina, Brazil, from 1994 to 2001.

From the total of 60 women, 12 did not show any neoplasic processes (group A), 12 had CIN I (group B), 12 had CIN II (group C), 12 had CIN III (group D), and 12 had invading carcinoma (group E) after hematoxylin and eosin (H&E) stain analysis. Patients who

Immunohistochemistry

The identification of stromal cells containing the MMP-2 antigen was made through the use of MMP-2 antibodies from Neomarkers (Labvision, Fremont, Calif) Ab-1 (lot 567P912/MS-567-P, in the 1:50 title).

Four micrometer sections were taken from paraffin blocks, deparaffinized in xylene, and rehydrated in ethanol. Endogenous peroxidase activity was blocked with 2% hydrogen peroxidase, followed by equine serum–blocking. MMP-2 mouse monoclonal antibody (Labvision) that was applied at a dilution of

Histometric and statistical analysis

To quantify stromal cells with MMP-2 expression, we applied a computer graphic analysis program, which is composed by a Samsung color video camera model SCS-135 (Samsung Camera, Seoul, Korea) mounted in a microscope (Nikon, Model Eclipse E-400, Nikon, Belmant, Calif), and a Pentium computer (Pentium, Laurenceville, Ga) with 64 MB of RAM memory equipped with a digitalization board and a software for computer image analyses (Imagelab-2000, São Paulo, Brazil). For the location of the areas to be

Results

Immunohistochemical reaction for MMP-2 showed the presence of stromal cells with higher positivity according to the severity of the studied group. The higher the histologic alteration, the larger the positivity for MMP-2 (Figure 1 and Table).

We observed that in group A (control) the average index of MMP-2 positive cells was 0.42% (SD 0.47). In group B (CIN I), the average index was 3.69% (SD 2.04). In CIN II (group C) and III (group D), the average percentage was 11.52% (SD 4.88) and 57.64% (SD

Comment

When and how the precursory lesions (NIC III) start invading the cervical stroma is still an obscure matter.8 The lack of concrete knowledge about the subject is demonstrated by a large amount of hypotheses trying to explain the physiopathology involved in the cervical carcinoma invasion.

Among them the proteolytic theory, also known as basement membrane lyses theory, is very attractive. It is based in the observation that the neoplasic membranes do not have the control of some adaptive

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    • Cited by (0)

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    Supported in part by grant FAPESP 01/07541-8.

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