Altered expression of HLA class I antigens in breast cancer: Association with prognosis

Abstract

Loss of surface expression of class I major histocompatibility antigens is commonly observed in malignant tumors and has been considered one of the mechanisms for escape from cytotoxic T cells. However, natural killer cells kill cells lacking HLA class I antigens. In the present study, we characterized by immunohistochemistry the HLA class I expression of breast carcinomas from 187 patients with TNM stages I and II, diagnosed 1981–1984, using β2‐microglobulin as a marker and evaluated the effect on survival with a follow‐up of up to 14 years. The largest group (48%) consisted of HLA class I–negative tumors (≤10% of cells stained), mixed expression (>10% and <80% of cells stained) was seen in 36% and only 15% were classified as HLA class I–positive (≥80% cells stained). No associations could be established with various clinicopathological parameters, such as tumor size, presence of lymph node metastases, histological grade, expression of hormone receptors, S phase and p53 mutations. There was no effect on recurrence‐free survival in the whole group; but among node‐negative patients (n = 86), those who had tumors with mixed HLA class I expression had a significantly higher probability of disease recurrence (OR = 3.42, p = 0.014) than patients with either HLA class I–positive or –negative tumors, particularly after more than 5 years. In node‐positive patients who received adjuvant therapy, this phenotype was not associated with disease recurrence. Int. J. Cancer 89:500–505, 2000. © 2000 Wiley‐Liss, Inc.

The Predictive Value of HLA Class I Tumor Cell Expression and Presence of Intratumoral Tregs for Chemotherapy in Patients with Early Breast Cancer

“…In concordance with previous studies, downregulation and loss of HLA class I was frequently seen in our study (9)(10)(11). Previous studies indicate that breast cancer is immunogenic and induces tumor-associated antigen-specific CTL (28).…”

“…Previous studies on HLA class I expression in breast cancer did not stratify for systemic therapy. Three studies have evaluated HLA class I expression and its effect on prognosis in breast cancer (10)(11)(12). Two studies found that HLA class I expression levels had no influence on the prognosis of patients, which is in concordance with our findings in patients that were not systemically treated (10,12).…”

“…Previous studies have shown that HLA class I expression is frequently downregulated in breast cancer (8,9). However, the reports on prognostic influence of HLA class I expression in breast cancer have contradictory results (10)(11)(12). Some found no significant correlation between percentage of tumor cells expressing HLA class I and survival of breast cancer patients (10,12).…”

“…However, the reports on prognostic influence of HLA class I expression in breast cancer have contradictory results (10)(11)(12). Some found no significant correlation between percentage of tumor cells expressing HLA class I and survival of breast cancer patients (10,12). In contrast, another study found that total loss of HLA class I was an independent indicator of good prognosis (11).…”

Increased expression of beta 2-microglobulin in multidrug-resistant tumour cells

“…This type 1 transmembrane glycoprotein is also a member of the MHC superfamily (Scheffer et al, 2002). In contrast to these findings of upregulated MHC related molecules, many studies have reported on downregulation or loss of expression of MHC class I related molecules in malignant cells (Kaklamanis et al, 1995;Korkolopoulou et al, 1996;Keskinen et al, 1997;Gudmundsdottir et al, 2000;Kamarashev et al, 2001;Palmisano et al, 2001). Ogretmen et al (1998) even reported the loss or decreased expression of b 2 -m in drug-resistant sublines of MCF-7 and HL60 cells, controlled by post-transcriptional mechanisms.…”