HLA-A, -B, -C Expression in Colon Carcinoma Mimics That of the Normal Colonic Mucosa and is Prognostically Relevant

Abstract

Whether human leukocyte antigen (HLA)-A, -B, -C expression has any predictive value on the prognosis of human malignancies remains controversial. Herein, monoclonal antibodies with preferential reactivity for HLA-A, HLA-B, and HLA-C (HCA2, HC10, and L31) were used to stain an archival collection of 291 formalin-fixed/paraffin-embedded tissues, comprising neoplastic lesions from stages II and III colon carcinoma patients (n=165), and the uninvolved, morphologically normal mucosae from a subset (n=126) of these patients. Marked staining variability was detected not only in the tumors as in previous studies, but also in the normal paired mucosae. HLA-A, -B, -C expression was similar in approximately two thirds of the available 126 normal/neoplastic pairs, confirming in vivo our previous observation that most tumor cells mimic the HLA phenotypes of their normal counterparts. Both up and down-regulation occurred in the remaining third of the pairs, but did not coincide with high and low expression, respectively, conventionally evaluated on the tumor lesion only. Remarkably, a "paired" evaluation, but not high or low expression in the tumor, was predictive of the clinical outcome. Deviations from the expression in the normal paired mucosa (both increases and decreases) of HCA2-reactive class I molecules (possibly HLA-A), and down-regulation of L31-reactive class I molecules (possibly HLA-C), particularly in tumors from stage II patients, correlated with poor 5-year overall and disease-free survival, hazard risk ranging from 2 to 6, approximately. Thus, a paired immunohistochemical comparison reveals a novel immune evasion strategy that may impact on the prognosis of colon carcinoma.

High expression of HLA-E in colorectal carcinoma is associated with a favorable prognosis

“…Accordingly, several immunohistochemical studies failed to confirm an association between HLA-A, -B, - C loss and poor prognosis [10-12], and our own studies were consistent with activation-inhibition models [13-16]. We showed that early-passage melanoma, breast carcinoma, and lung carcinoma cells, like virus-infected cells, avoid both extremes of overly low or high HLA class I expression, which would expose them to lysis by NK and CTLs, respectively.…”

The bodies fight against cancer: is human leucocyte antigen (HLA) class 1 the key?

“…When HC10 in isolation with b2-m was studied, reduced expression of HLA class 1 was predictive of poor outcome. The observation by Benevolo et al (2007) and Menon et al (2002) that HC10 expression alone was not associated with outcome further supports the importance of b2-m in antigen representation.…”

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.…”