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The Immunoexpression of Heparanase 2 in Normal Epithelium, Intraepithelial, and Invasive Squamous Neoplasia of the Cervix

Marques, Renato Moretti MD1,2; Focchi, Gustavo Rubino PhD3; Theodoro, Thérèse Rachell MD4; Castelo, Adauto PhD5; Pinhal, Maria Aparecida PhD4; Nicolau, Sérgio Mancini PhD1

Journal of Lower Genital Tract Disease: July 2012 - Volume 16 - Issue 3 - p 256–262
doi: 10.1097/LGT.0b013e3182422c69
Original Articles

Objective: Heparanase 2 (HPSE2) is expressed in various tissues, including the brain, intestine, prostate, breast, and endometrium. The aim of this study was to investigate the role of HPSE2 in cervical carcinogenesis, which has not been clarified to date.

Materials and Methods: The immunoexpression of HPSE2 in normal and neoplastic cervical squamous epithelia was determined using a semiquantitative (SQ) method and an index of expression (IE) method, using Image Lab Software. A total of 230 cervical tissue samples were analyzed and segregated into the following diagnostic groups: normal (27.4%), cervical intraepithelial neoplasia 1 (CIN 1, 15.2%), CIN 2 (16.5%), CIN 3 (15.2%), and invasive neoplasia (25.7%). The mean HPSE2 expression in the normal group was significantly lower than that of the other groups individually or combined (p < .001, for all combinations). The immunoexpression via the SQ method was significantly greater in the CIN 3 group compared with that in the CIN 1 group (p = .02). The mean immunoexpression of the high-grade squamous intraepithelial lesion groups was significantly greater than those of the normal and low-grade squamous intraepithelial lesion groups (p < .001) and lower compared with that of the invasive neoplasia group (p < .001). There were no statistically significant differences in the immunoexpression of HPSE2 among the different clinical states within the invasive neoplasia group.

Conclusions: The SQ method produced a greater sensitivity and specificity than did the index of expression method. There was a progressive increase in the mean HPSE2 immunoexpression according to the severity of the cervical lesion from the low-grade squamous intraepithelial lesion group to the invasive neoplasm group, whereas the normal group displayed the lowest level of expression. This is a novel study concerning HPSE2 in the cervix and cervical cancer carcinogenesis.

1Department of Gynecology, Division of Oncological Gynecology, Federal University of São Paulo - Paulista School of Medicine Professor, São Paulo, Brazil; 2Department of Obstetrics and Gynecology, University of Taubaté, Taubaté, Brazil; 3Department of Pathology, Federal University of São Paulo - Paulista School of Medicine, São Paulo, Brazil; 4Department of Biochemistry of the College of Medicine of ABC, São Paulo, Brazil; and 5Department of Medicine, Division of Infectious Diseases, Federal University of São Paulo - Paulista School of Medicine, São Paulo, Brazil

Reprint requests to: Renato Moretti Marques, MD, Department of Gynecology, Division of Oncological Gynecology, Universidade Federal de São Paulo - Paulista School of Medicine, Rua Borges lagoa, 783, Vila Clementino, São Paulo, Brazil 04038-032. E-mail:

The authors have no conflicts of interest to disclose.

©2012The American Society for Colposcopy and Cervical Pathology