Strong HLA-DR expression in large bowel carcinomas is associated with good prognosis

Andersen, Solveig Norheim; Rognum, Torleiv O.; Lund, Eiliv; Meling, Gunn Iren; Hauge, Siri Helene

doi:10.1038/bjc.1993.290

Cited by 65 publications

(42 citation statements)

References 32 publications

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“…This scenario will offer an explanation for the fact that K-ras mutations are less frequent in carcinomas than in adenomas. Furthermore, this view would be compatible with the observation that class II expression is associated with a better prognosis in colorectal carcinomas (Norheim Andersen et al, 1993).…”

Section: Discussionsupporting

confidence: 76%

“…The same investigator (SNA) was responsible for the fluorescence scoring throughout the study. Reproducibility studies of a similar fluorescence scoring system have been published previously (Norheim Andersen et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

“…The significance of class I and II MHC expression in the immune recognition of human tumours is a matter of dispute. Recently we demonstrated better survival of patients with HLA-DR-positive large bowel carcinomas than of those without (Norheim Andersen et al, 1993). Others, however, have been unable to show such a relationship (Ghosh et al, 1986;Moller et al, 1991).…”

mentioning

confidence: 91%

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K-ras mutations and HLA-DR expression in large bowel adenomas

Andersen

Breivik²,

Løvig³

et al. 1996

Br J Cancer

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Summary A total of 72 sporadic colorectal adenomas in 56 patients were studied for the presence of point mutations in codons 12 and 13 of the K-ras gene and for HLA-DR antigen expression related to clinicopathological variables. Forty K-ras mutations in 39 adenomas were found (54%): 31 (77%) in codon 12 and nine (23%) in codon 13. There was a strong relationship between the incidence of K-ras mutations and adenoma type, degree of dysplasia and sex. The highest frequency of K-ras mutations was seen in large adenomas of the villous type with high-grade dysplasia. Fourteen out of 15 adenomas obtained from 14 women above 65 years of age carried mutations. HLA-DR positivity was found in 38% of the adenomas, large tumours and those with high-grade dysplasia having the strongest staining. Coexpression of K-ras mutations and HLA-DR was found significantly more frequently in large and highly dysplastic adenomas, although twoway analysis of variance showing size and grade of dysplasia to be the most important variable. None of the adenomas with low-grade dysplasia showed both K-ras mutation and HLA-DR positivity (P=0.004). K-ras mutation is recognised as an early event in colorectal carcinogenesis. The mutation might give rise to peptides that may be presented on the tumour cell surface by class II molecules, and thereby induce immune responses against neoplastic cells.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 91%

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K-ras mutations and HLA-DR expression in large bowel adenomas

Andersen

Breivik²,

Løvig³

et al. 1996

Br J Cancer

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“…A pronounced peri-and intratumoral lymphocytic infiltrate has repeatedly been shown to be related to a better prognosis (Jass, 1986;Halvorsen and Seim, 1989;Di Giorgio et al, 1992). Our results on MHC II expression and appearance of CD4+ lymphocytes are, thus, in good agreement with the association between strong expression of HLA-DR and good prognosis as reported by Andersen et al (1993). In contrast to our results, Daar et al (1982) did not find any correlation between the MHC II expression and the degree of mononuclear cell infiltration.…”

Section: Discussioncontrasting

confidence: 55%

Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis

Håkansson

Adell²,

Boeryd³

et al. 1997

Br J Cancer

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Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis L HAkansson1, G Adell1, B Boeryd2, F Sjogren3 and R Sjodahl4Departments of 'Oncology, 2Pathology, 3Clinical Immunology and 4Surgery, University Hospital of Linkoping, S-581 85 Linkoping, Sweden Summary Local immunoregulation mediated by mononuclear tumour-infiltrating cells is considered of importance for tumour progression of colorectal cancer, although the balance between immunosuppressor and cytotoxic activities is unclear. Colorectal cancers from 26 patients were investigated using a panel of monoclonal antibodies in order to identify subsets of mononuclear inflammatory cells and to study their pattern of distribution in relation to tumour stage and cytotoxic immune reactivity against the tumour. In all but five tumours, mononuclear cells, lymphocytes or monocytes were present in fairly large numbers, particularly in the stroma. The infiltration of CD4+ mononuclear cells predominated over the CD8+ subset. Infiltration near the tumour cells was found in four cancers only. Stromal infiltration of CD11c+ macrophages was found in all but eight tumours. Small regressive areas, in which the histological architecture of the tumours was broken down, were found in 17 tumours with intense or moderate infiltration by CD4+ lymphocytes or CD1 1 c+ macrophages. Probably this destruction of tumour tissue was caused by cytotoxic activity of the tumour-infiltrating mononuclear cells. In Dukes' class A and B tumours, CD4+ lymphocytes predominated over CD4+ cells with macrophage morphology, but the latter were increasingly found in Dukes' class C and D disease. The occurrence of MHC Il-positive macrophages and lymphocytes in different Dukes' classes was similar to that of CD4+ cells. In contrast to this, CD11c+ and CD11a+ cells were more frequent in Dukes' A and B class tumours compared with Dukes' C and D. Four out of nine tumours of the latter stages showed a poor inflammatory reaction. The interpretation of our results is that the subsets of tumourinfiltrating mononuclear cells change with advancing Dukes' class and that the local immune control is gradually broken down in progressive tumour growth, even if some cytotoxic activity is still present.

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“…In that regard, the prognoses of colorectal cancers strongly correlate with the infiltration of CD4 þ lymphocytes, which recognize tumor antigen presented with MHC class II molecules (Andersen et al, 1993;Lovig et al, 2002), so that colorectal cancers that lack HLA-DR have worse prognoses than those that do (Lovig et al, 2002). For these reasons, understanding the molecular mechanisms regulating expression of MHC class II molecules may represent an important step toward developing efficient immunotherapies with which to treat gastrointestinal cancers.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic inactivation of class II transactivator (CIITA) is associated with the absence of interferon-γ-induced HLA-DR expression in colorectal and gastric cancer cells

et al. 2004

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Tightly regulated at the level of transcription, expression of MHC class II molecules varies significantly among gastrointestinal cancers. High levels of MHC class II expression are often associated with a better prognosis, which is indicative of the involvement of CD4 þ lymphocytes in tumor suppression, but the molecular mechanism by which MHC class II expression is regulated remains unclear. In the present study, we investigated the expression of one inducible MHC class II molecule, HLA-DR, and its coactivators in a panel of colorectal and gastric cancer cell lines. Interferon-c induced expression of HLA-DR in 14 of 20 cell lines tested; the remaining six cell lines did not express HLA-DR. Analysis of the expression of transcription factors and coactivators associated with HLA-DR revealed that the loss of CIITA expression was closely associated with the absence of HLA-DR induction. Moreover, DNA methylation of the 5 0 CpG island of CIITA-PIV was detected in all cancer cells that lacked CIITA. The methylation and resultant silencing of CIITA-PIV depended on the activities of two DNA methyltransferases, DNMT1 and DNMT3B, and their genetic inactivation restored CIITA-PIV expression. It thus appears that CIITA methylation is a key mechanism that enables some gastrointestinal cancer cells to escape immune surveillance.

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Strong HLA-DR expression in large bowel carcinomas is associated with good prognosis

Cited by 65 publications

References 32 publications

K-ras mutations and HLA-DR expression in large bowel adenomas

K-ras mutations and HLA-DR expression in large bowel adenomas

Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis

Epigenetic inactivation of class II transactivator (CIITA) is associated with the absence of interferon-γ-induced HLA-DR expression in colorectal and gastric cancer cells

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