Clinical impact of HLA class I expression in rectal cancer

Purpose To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal carcinomas. Experimental design Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistoche...

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Bibliographic Details
Published in:Cancer Immunology, Immunotherapy Immunotherapy, 2008-05, Vol.57 (5), p.601-609
Main Authors: Speetjens, Frank M., de Bruin, Elza C., Morreau, Hans, Zeestraten, Eliane C. M., Putter, Hein, van Krieken, J. Han, van Buren, Maaike M., van Velzen, Monique, Dekker-Ensink, N. Geeske, van de Velde, Cornelis J. H., Kuppen, Peter J. K.
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Antineoplastic agents
Biological and medical sciences
Biomarkers, Tumor - analysis
Cancer Research
Clinical Trials as Topic
Colorectal cancer
Disease-Free Survival
Gastroenterology. Liver. Pancreas. Abdomen
Histocompatibility Antigens Class I - biosynthesis
Humans
Immunohistochemistry
Immunology
Immunotherapy
Kaplan-Meier Estimate
Leukocytes
Medical prognosis
Medical sciences
Medicine
Medicine & Public Health
Metastasis
Microsatellite Instability
Oncology
Original
Original Article
Pathology
Pharmacology. Drug treatments
Prognosis
Radiation therapy
Rectal Neoplasms - genetics
Rectal Neoplasms - metabolism
Rectal Neoplasms - mortality
Stomach. Duodenum. Small intestine. Colon. Rectum. Anus
Surgery
Tissue Array Analysis
Tumors
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Summary:Purpose To determine the clinical impact of human leukocyte antigen (HLA) class I expression in irradiated and non-irradiated rectal carcinomas. Experimental design Tumor samples in tissue micro array format were collected from 1,135 patients. HLA class I expression was assessed after immunohistochemical staining with two antibodies (HCA2 and HC10). Results Tumors were split into two groups: (1) tumors with >50% of tumor cells expressing HLA class I (high) and (2) tumors with ≤50% of tumor cells expressing HLA class I (low). No difference in distribution or prognosis of HLA class I expression was found between irradiated and non-irradiated patients. Patients with low expression of HLA class I (15% of all patients) showed an independent significantly worse prognosis with regard to overall survival and disease-free survival. HLA class I expression had no effect on cancer-specific survival or recurrence-free survival. Conclusions Down-regulation of HLA class I in rectal cancer is associated with poor prognosis. In contrast to our results, previous reports on HLA class I expression in colorectal cancer described a large population of patients with HLA class I negative tumors, having a good prognosis. This difference might be explained by the fact that a large proportion of HLA negative colon tumors are microsatellite instable (MSI). MSI tumors are associated with a better prognosis than microsatellite stable (MSS). As rectal tumors are mainly MSS, our results suggest that it is both, oncogenic pathway and HLA class I expression, that dictates patient’s prognosis in colorectal cancer. Therefore, to prevent confounding in future prognostic analysis on the impact of HLA expression in colorectal tumors, separate analysis of MSI and MSS tumors should be performed.
ISSN:0340-7004
1432-0851
DOI:10.1007/s00262-007-0396-y