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Immunohistochemical Expression of Heparanases 1 and 2 in Benign Tissue and in Invasive Neoplasia of the Endometrium: A Case-Control Study
  1. Roney Cesar Signorini, MD, PhD*,
  2. Gustavo Rubino de Azevedo Focchi, MD, PhD,
  3. Thérèse Rachell Theodoro, BS, MsC,
  4. Maria Aparecida Silva Pinhal, PhD and
  5. Sergio Mancini Nicolau, MD, PhD*
  1. *Departments of Gynecology and
  2. Pathology, Universidade Federal de São Paulo, São Paulo; and
  3. Department of Biochemistry, Faculdade de Medicina do ABC, Santo André, São Paulo, Brazil.
  1. Address correspondence and reprint requests to Gustavo Rubino de Azevedo Focchi, MD, PhD, Rua São Benedito, 2653 - apto. 51, São Paulo, Brazil, CEP: 04735–005. E-mail: gustavo.focchi{at}


Objectives Our purpose was to compare the expression of heparanase isoforms, in normal and in neoplastic endometrium. In a pioneering way, we sought to evaluate the expression of heparanase 1 (HPSE1) and heparanase 2 (HPSE2) in glandular and in stromal tissues.

Methods This is a case-control study, conducted retrospectively in a public hospital, using paraffin blocks of endometrial tissue from patients admitted from 2002 to 2011 with and without endometrial cancer, with regard to the immunohistochemical expression of HPSE1 and HPSE2. The paraffin blocks were used for tissue microarray analysis and immunohistochemistry study in glandular and stromal tissues.

Results In the study period, 195 participants were enrolled, 75 with and 120 without cancer. There was no significant difference between them regarding HPSE1 expression, both in gland and in stromal tissues. Heparanase 1 expression in the glandular tissue was more frequent among those with high-grade carcinoma, compared with patients with carcinoma type I. The difference in the expression of HPSE2 was significant between groups: it was less frequent in the controls than in the patients with cancer in the glandular tissue. In the stromal tissue, HPSE2 expression was significantly higher in the controls than in the patients with cancer and different when patients of the secretory endometrium subgroup were compared with those with hypotrophic, proliferative endometriums or with architectural disorders. No significant difference was found in the heparanase expressions in patients with cancer according to prognosis factors.

Conclusions Heparanase 1 is more intensely expressed in the glandular tissue of high-grade compared with type I carcinomas. Heparanase 2 is more intensely expressed in the glandular tissue of cancer than in nonneoplastic endometrium, whereas the HPSE2 expression in the stromal tissue is higher in the nonneoplastic controls compared with the group of patients with cancer mainly in the secretory endometrium. This suggests that HPSE2 might be stimulated by progesterone, with a possible antineoplastic role, antagonist to HPSE1, to be further investigated.

  • Heparanase
  • Endometrial neoplasms
  • Biological markers
  • Extracellular matrix
  • Immunohistochemistry

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  • The authors declare no conflicts of interest.