The GSTT1 polymorphism of the glutathione S-transferase system in the intratumoral microvessel density of breast cancer patients.
It is well established that hypoxic microenvironment contributes to breast cancer progression by activation of transcriptional genes that promote angiogenesis. By promoting the antioxidant activity of glutathione, glutathione S-transferases (GSTs) are likely to facilitate the hypoxia-inducible factor-1α (HIF-1α) activity, therefore stimulating the angiogenesis. We investigated herein the influence of the GSTM1 and GSTT1 polymorphisms in the intratumoral angiogenesis of 87 patients with sporadic breast cancer. The intratumoral microvessel density (IMVD) of formalin-fixed paraffin-embedded tissues samples from all patients was determined by immunohistochemistry. The high IMVD was defined as a median microvessel counting higher than 18.7 after the analysis of histogram with all the results. The high IMVD was more common in patients with the GSTT1 wild genotype than in those with the GSTT1 null genotype (P = 0.04). Our results suggest, for the first time, that the GSTT1 polymorphism constitutes an inherited determinant of intratumoral angiogenesis in sporadic breast cancer.
Lourenço
Gustavo J
GJ
Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Rua Alexander Fleming, 181, Cidade Universitária Zeferino Vaz, Distrito de Barão Geraldo, Campinas, São Paulo, Brazil.
Schenka
André A
AA
Cardoso-Filho
Cassio
C
Pinto
Glauce A
GA
Costa-Gurgel
Maria S
MS
Vassallo
José
J
Lima
Carmen Silvia Passos
CS
D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D055806:Microvessels / Q000201:enzymology; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics*; D011110:Polymorphism, Genetic
D005982:Glutathione Transferase; C413545:glutathione S-transferase T1