The relationship among HLA-I, HLA-G and HLA-E immunohistochemistry expression, assessed by image analyses system, in breast cancer
Authors: Gisela B. Rolfsen, Roberta Aparecida Duarte, Nicolino Lia Neto, Leonardo Alberto Cunha, Helio Humberto Angotti Carrara, Eduardo Antonio Donadi, Maria Alice Guimarães Gonçalves, Edson Garcia Soares, Christiane Pienna Soares
Journal: Cancer Research (2006)

623   Introduction: Among the different mechanisms by which cancer elude the immune system, alterations in the exppression of human leukocyte antigen (HLA) may play a crucial role by impairing the HLA molecules interaction with T and natural killer (NK) cells specific receptors. The tumor escape from host immunosurveillence could related to breast cancer progression to metastasis, recurrence and patient9s death. Loss or deregulation of HLA I expression it seems to be lost on the cell tumor surface and it might represent a mechanism for neoplastic cells to escape CTL-mediated killing, allowing tumor dissemination and metastasis. Likewise, high expression of HLA- E and - G are nonclassic HLA class I molecules at the tumor cell surface might allows them to escape -T and NK cell immune surveillance throught different pathways. Objective: Considering that deregulation of HLA expression could represent a potential mechanism to breast carcinogenesis and metastasis, the aim of the present was analyzed HLA-I, HLA-E and HLA-G immunohistochemistry expression in invasive ductal carcinoma (IDC) of the breast, according anatomoclinical paramethers of agressiveness and metastatic tumor behaviour. Material and Methods: Fifty two IDC of the breast biopsies were stratified according histological differentiation (well, moderately and poorly differentiated) and to the presence of metastasis in axillary lymphonodes. HLA-I, HLA-G and HLA-E expression were performed by immunoperoxidase and the expression was quantified by computer-assisted image analyze equipament (Qwin Image Analysis System, LEICA, Wetzlar,Germany).Results: Thirty-one (59.6.%) of the 52 IDC breast biopsies presented high expression of HLA-G and 14 (26.9 %) out of 52 HLA-E overexpression. Negative expression to HLA-G and HLA-E were observed in, respectively, 21(38.9%) and 39(72.2%) out of 52 IDC breast biopsies. In contrast, 11( 21.2%) of the 52 breast biopsies presented HLA-I high expression of and 41(78.8%) of the 52 low expression. Twenty-four(41.2%) of out 52 patients had low HLA-I expression and high HLA-G expression while 11(21.2%) possessed low HLA-I expression and high HLA-E expression. Moreover, all these patients (100%) were moderately (12/24 HLA-G and 7/11 HLA-E and poorly (12/24 HLA-G and 5/11 HLA-E) differentiated breast tumor. No well-differentiated breast tumor presented this relationship among HLA-I, HLA-G and HLA-E. However, no statistic difference was found among downregulation HLA-I and HLA-G and -E upregulation expression and metastasis in axillary lymphonodes.Conclusion: These results suggest that, throught different mechanisms, the downregulation of HLA-I and the upregulation of HLA-G and -E, is associated to immune response evasion and breast cancer agressiveness.(financial support: FAPESP, CNPq and CAPES).