Gains and Losses of HLA Class II (DR) and CD4 in Atypical Hyperplasia, Carcinoma in situ and Infiltrating Ductal Carcinoma of the Breast

Abstract

Aim: Breast cancer is a frequent cause of death among women with gynaecologic malignancies despite the introduction of combination chemotherapy. There is therefore a need for new therapeutic strategies for patients with breast cancer, such as cellular immunotherapy. In this immunohistochemical study we analyzed the epithelial expression of major histocompatibility complex (MHC) class II (HLA-DR) on atypical and malignant primary mammary epithelial cells, as well as the magnitude of the stromal T lymphocytes (T4 subset) at the tumor site. Experimental design: The study was carried out retrospectively in tumor tissue from 82 patients with mammary lesions (31 cases of atypical ductal hyperplasia -ADH-, 12 cases of ductal carcinoma in situ –DCIS- and 39 cases of infiltrating ductal carcinoma not otherwise specified -IDC-NOS). Medullary carcinomas were not included in our investigation. Material used had been formalin fixed and paraffin embedded. Results: HLA class II (DR) was expressed in 20 of 31 ADHs (64.5%), in 4 of 12 DCISs (33.3%), and in 10 of 39 IDC-NOSs (25.6%). CD4 was expressed in 9 of 31 ADHs (29%), in 5 of 12 DCISs (42%), and in 26 of 39 IDCNOSs (67%). Conclusions: The results showed decreased epithelial expression of HLA class II (DR) and increased stromal expression of CD4, as the lesion progressed to malignancy. Gradual loss of epithelial HLA class II expression might be a manifestation of cellular differentiation from the atypical form versus the malignant one, signaling simultaneously a selective effect on the response capacity of the immune system.

Spatially-resolved quantification of proteins in triple negative breast cancers reveals differences in the immune microenvironment associated with prognosis

“…3E). These findings validate the DSP detection of HLA-DR expression in epithelial tumor ROIs www.nature.com/scientificreports www.nature.com/scientificreports/ and confirm that a subset of patient-derived breast cancer epithelial cells can express MHCII proteins such as HLA-DR, which is consistent with our previous observations 2, 3 , as well as with those of other investigators 4,[17][18][19][20][21] .…”

Heterogeneity of mammary lesions represent molecular differences

“…In 4w-11 tumors, CEBPA, which is associated with breast cancer progression [27] was down-regulated and CEBPB, a gene found to be up-regulated in breast cancer as well as mouse mammary tumors [28], is up-regulated. Moreover, the 4w-11 tumors exhibited down-regulation of actin, myosin, Ig, and MHC class 2 transcripts, which have been shown to be decreased in highly metastatic breast cancer cell lines [29], as well as decreased during progression to tumor [30]. 8w-B tumors had up-regulation of PLK [31] and 8w-D tumors had up-regulation of Epha2 [32].…”

Pediatric adrenocortical tumors: morphological diagnostic criteria and immunohistochemical expression of matrix metalloproteinase type 2 and human leucocyte-associated antigen (HLA) class II antigens

“…It is not yet known when these antigens appear in the adrenal cortex, but they are probably involved in cellular differentiation. Loss of expression of HLA class antigens or deregulation has been reported in a great variety of tumors, including breast, cervix, larynx, colon, and pancreas cancers [26][27][28][29][30][31][32]. In a study of gene expression by microarray analysis, carried out on 24 pediatric ACTs (5 adenomas, 18 carcinomas, 1 tumor classified as indeterminate for malignancy), West et al [12] identified 52 probe sets for which significant differences were found when comparing adrenocortical adenomas versus carcinomas.…”