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Multicenter Study
. 2008 May;57(5):601-9.
doi: 10.1007/s00262-007-0396-y. Epub 2007 Sep 15.

Clinical impact of HLA class I expression in rectal cancer

Frank M Speetjens  1 , Elza C de Bruin, Hans Morreau, Eliane C M Zeestraten, Hein Putter, J Han van Krieken, Maaike M van Buren, Monique van Velzen, N Geeske Dekker-Ensink, Cornelis J H van de Velde, Peter J K Kuppen
Affiliations
Multicenter Study

Clinical impact of HLA class I expression in rectal cancer

Frank M Speetjens et al. Cancer Immunol Immunother. 2008 May.

Abstract

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 < or =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.

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Figures

Fig. 1
Fig. 1
Examples of HCA2 and HC10 immunohistochemical staining of rectal tumors; a–c HCA2, d–f HC10 expression. a, d Expression of HLA class I in >50% tumor cells; b, e expression of HLA class I in <50% tumor cells; c, f epithelial cells show total absence for HCA2 or HC10 and only stromal and infiltrative cells show positive staining for HCA2 or HC10; Original magnification ×20
Fig. 2
Fig. 2
Examples of Kaplan–Meier curves showing overall survival and cancer specific survival for irradiated and non-irradiated patients (a–d). Kaplan–Meier curves for overall survival (a, b) and cancer specific survival (c, d); curves show prognosis for non-irradiated (a, c) and irradiated patients (b, d) for HLA class I expression in more than 50% of the tumor cells (high) versus expression in less than 50% of the tumor cells (low). P value is based on univariate log rank analyses
See this image and copyright information in PMC

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