Abstract |
The prognosis of newly diagnosed colorectal cancer patients relies mostly on tumor-node metastasis classification. However, analyses of tumor-infiltrating lymphocytes and several molecular markers have also shown promising prognostic value. Mutations in the proto-oncogene KRAS, which occur early in colorectal carcinogenesis, have been demonstrated to be common in human colorectal cancer (CRC); however, their prognostic significance remains controversial. We examined the correlations between KRAS mutational status and tumor-infiltrating immune cells with respect to CRC recurrence. Mutations in KRAS were identified in 45.5% of the primary carcinomas in our cohort of patients: 65% in codon 12 and 35% in codon 13. Although codon 13 KRAS mutations were associated with disease relapse, they were present in both disease-free and relapsed patients. However, disease-free and relapsed patients differed markedly in their patterns of tumor-infiltrating immune cells. There was a trend toward decreased density of tumor-infiltrating lymphocytes (TILs) within the group of relapsed cases. In addition, relapsed patients with codon 13 mutations had markedly lower levels of tumor-infiltrating mature DC-LAMP(+) dendritic cells (DCs) and higher frequency of CD1a(+) cells compared with disease-free patients. Our data suggest that CRC patients with low levels of TILs, a high CD1a(+)/DC-LAMP(+) tumor-infiltrating DC ratio, and a KRAS mutation in codon 13 are at a high risk of disease recurrence.
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Authors | Petr Kocián, Monika Šedivcová, Jan Drgáč, Kateřina Cerná, Jiří Hoch, Roman Kodet, Jiřina Bartůňková, Radek Špíšek, Anna Fialová |
Journal | Human immunology
(Hum Immunol)
Vol. 72
Issue 11
Pg. 1022-8
(Nov 2011)
ISSN: 1879-1166 [Electronic] United States |
PMID | 21884745
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Antigens, CD1
- Biomarkers, Tumor
- CD1a antigen
- Cell Adhesion Molecules, Neuronal
- GPI-Linked Proteins
- KRAS protein, human
- MAS1 protein, human
- Proto-Oncogene Mas
- Proto-Oncogene Proteins
- limbic system-associated membrane protein
- Proto-Oncogene Proteins p21(ras)
- ras Proteins
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Topics |
- Antigens, CD1
(biosynthesis)
- Biomarkers, Tumor
(genetics)
- Carcinoma
(diagnosis, genetics, pathology, physiopathology)
- Cell Adhesion Molecules, Neuronal
(biosynthesis)
- Cell Differentiation
(genetics)
- Cell Movement
(genetics)
- Colorectal Neoplasms
(diagnosis, genetics, pathology, physiopathology)
- DNA Mutational Analysis
- Dendritic Cells
(immunology, metabolism, pathology)
- Early Detection of Cancer
- Female
- Follow-Up Studies
- GPI-Linked Proteins
(biosynthesis)
- Genetic Association Studies
- Humans
- Lymphocytes, Tumor-Infiltrating
(immunology, metabolism, pathology)
- Male
- Mutation
(genetics)
- Neoplasm Recurrence, Local
- Prognosis
- Proto-Oncogene Mas
- Proto-Oncogene Proteins
(genetics)
- Proto-Oncogene Proteins p21(ras)
- ras Proteins
(genetics)
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