Immunohistochemically demonstrated expression of HLA‐DR antigen in colorectal adenocarcinomas and its relation to clinicopathological features

Morita, Mika; Tanaka, Kanji; Kuroda, Hiroshi; Tsuji, Masazumi; Ookusa, Tokio; Takada, Hideho; Okamura, Atsushi; Hioki, Koshiro

doi:10.1002/jso.2930590407

Cited by 19 publications

(16 citation statements)

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“…Patients with HLA-DR positive carcinomas showed significantly better overall survival than in patients with DR negative carcinomas, which is consistent with several other studies (Gutierrez et al, 1987;Norheim Andersen et al, 1993;Lazaris et al, 1995;Morita et al, 1995;Kunihiro et al, 1998). Quite surprisingly, stratified analyses of survival with respect to MSI status, differentiation, ploidi and tumour localisation disclosed that in MSS/MSI-L tumours, in tumours with aneuploid DNA pattern and in moderately differentiated tumours, strong HLA-DR expression turned out to be a marker for favourable prognosis ( Figure 3A,B,C).…”

Section: Discussionsupporting

confidence: 90%

“…The MHC encodes for three classes of cell antigens: class I (HLA-A, -B, -C), class II (HLA-DR, -DQ, -DP) and class III (Klein and Sato, 2000). HLA-DR antigen expression is usually not present in the epithelium of the large bowel, but may be turned on in inflammatory disorders, such as ulcerative colitis (Rognum et al, 1987), Crohn's disease and in colorectal tumours (Rognum et al, 1983;Gutierrez et al, 1987;Norheim Andersen et al, 1993;Chang and Sohn, 1995;Lazaris et al, 1995;Morita et al, 1995;Kunihiro et al, 1998). HLA-DR antigen expression on tumour cells is a marker of good prognosis in large bowel carcinomas (Gutierrez et al, 1987;Norheim Andersen et al, 1993;Lazaris et al, 1995;Morita et al, 1995;Kunihiro et al, 1998).…”

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confidence: 99%

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Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis

et al. 2002

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Progression of colorectal cancer may follow either of two main genetic routes: the chromosome- or microsatellite-instability pathways. Association between the patients' prognosis and microsatellite instability has been questioned. Improved survival has previously been found in patients with expression of HLA-DR antigens on their tumour cells. In this study, the expression of HLA-DR antigen was investigated by immunohistochemistry in 357 large bowel carcinomas stratified by microsatellite instability status. Sixteen per cent of the tumours showed strong HLA-DR expression and 35% had weak DR expression. We confirmed that patients with strong positive HLA-DR staining had improved survival ( P <0.001) compared to patients with no HLA-DR expression. Strong epithelial HLA-DR staining was significantly associated with high level of microsatellite instability ( P <0.001). In the subgroup of tumours with characteristics typical of the chromosomal instability phenotype, i.e. in microsatellite-stable tumours, the patients positive for the HLA-DR determinants showed better survival than those without HLA-DR expression. The protective effect of HLA-DR expression on survival was confirmed by multivariate analysis, both in the whole patient group and in the microsatellite-stable/microsatellite instability-low group. This might be explained by enhanced T-cell mediated anti-tumour immune responses against tumour cells in the HLA-DR positive tumours. The finding of better patient survival in the subgroup of strong HLA-DR positive microsatellite-stable tumours may have clinical implications for these patients. British Journal of Cancer (2002) 87 , 756–762. doi: 10.1038/sj.bjc.6600507 www.bjcancer.com © 2002 Cancer Research UK

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Section: Discussionsupporting

confidence: 90%

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confidence: 99%

Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis

et al. 2002

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“…A positive relationship between HLA-DR expression and prognosis was found in gastric (Hilton and West, 1990;Ma et al, 1994;Cabrera et al, 1995;Ishigami et al, 1998) and colorectal carcinoma (Rognum et al, 1983;Gutierrez et al, 1987;Norheim Andersen et al, 1993;Chang and Sohn, 1995;Lazaris et al, 1995;Morita et al, 1995;Kunihiro et al, 1998;Lovig et al, 2002). Discordant findings regarding the levels of HLA-DR expression were reported in breast cancer (Natali et al, 1983;Bernard et al, 1984;Hurlimann and Saraga, 1985;Bartek et al, 1987;Walker, 1987, 1988;Koretz et al, 1989;Moller et al, 1989;Brunner et al, 1991;Concha et al, 1991;Lucin et al, 1994).…”

Section: Distribution Of Hla-dr Antigens In Solid Malignanciesmentioning

confidence: 91%

Targeted therapy of solid malignancies via HLA class II antigens: a new biotherapeutic approach?

et al. 2003

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Intracellular signals, delivered in professional antigenpresenting cells following the engagement of major histocompatibility complex (MHC) class II molecules, activate a variety of cellular functions that also contribute to efficient antigen presentation. As far as human malignancies, the signaling ability of human leukocyte antigens (HLA) class II molecules is a rather wellcharacterized event in hematologic tumors; in contrast, very limited evidences are available in solid neoplasias of different histotypes that may constitutively express HLA class II antigens. Among solid malignancies, a significant proportion of human cutaneous melanomas have been shown to express HLA class II molecules, and cutaneous melanoma undoubtedly represents a 'model disease' to investigate tumor immunobiology, to unveil the molecular basis underlying the interactions between neoplastic cells and host's immune system, and ultimately to set up new bio-immunotherapeutic approaches. Upcoming preclinical evidences unveil a signaling potential of HLA-DR antigens expressed on melanoma cells, and suggest for the clinical implication of HLA class II molecules as novel therapeutic targets. Therefore, in this review, we will focus on the emerging role of HLA class II antigens as intracellular signal transducing elements in neoplastic cells of the melanocytic lineage, emphasizing their foreseeable role in targeted therapy of human melanoma and potentially of HLA class II antigens-positive tumors of different histology.

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“…However, the available information about the prognostic significance of HLA class II antigen expression in cancers is conflicting (Table 3). While constitutive HLA class II antigen expression was reported to be associated with a favorable prognosis in some tumor types, e. g. CRC and larynx squamous cell carcinoma, [71][72][73][74] it was associated with higher metastatic dissemination, increased tumor stage and reduced patients' survival in other malignancies, such as melanoma and cervical carcinoma. [75][76][77] Conflicting is the information about the clinical relevance of HLA class II antigen expression in osteosarcoma; however, the number of tumors analyzed is too small to draw conclusions.…”

Section: Deregulation Of Hla Class II Apm Components In Malignant Cellsmentioning

confidence: 99%

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

2017

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The human leukocyte antigen (HLA) class II antigen-processing machinery (APM) presents to cognate CD4 C T-cells antigenic peptides mainly generated from exogeneous proteins in the endocytic compartment. These CD4 C T cells exert helper function, but may also act as effector cells, thereby recognizing HLA class II antigen-expressing tumor cells. Thus, HLA class II antigen expression by tumor cells influences the tumor antigen (TA)-specific immune responses and, depending on the cancer type, the clinical course of the disease. Many types of human cancers express HLA class II antigens, although with marked differences in their frequency. Some types of cancer lack HLA class II antigen expression, which could be due to structural defects or deregulation affecting different components of the complex HLA class II APM and/or from lack of cytokine(s) in the tumor microenvironment. In this review, we have summarized the information about HLA class II antigen distribution in normal tissues, the structural organization of the HLA class II APM, their expression and regulation in malignant cells, the defects, which have been identified in malignant cells, and their functional and clinical relevance.

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Immunohistochemically demonstrated expression of HLA‐DR antigen in colorectal adenocarcinomas and its relation to clinicopathological features

Cited by 19 publications

References 19 publications

Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis

Strong HLA-DR expression in microsatellite stable carcinomas of the large bowel is associated with good prognosis

Targeted therapy of solid malignancies via HLA class II antigens: a new biotherapeutic approach?

HLA class II antigen-processing pathway in tumors: Molecular defects and clinical relevance

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