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Tumor-infiltrating lymphocytes and dendritic cells in human colorectal cancer: their relationship to KRAS mutational status and disease recurrence
P. Kocián, M. Šedivcová, J. Drgáč, K. Cerná, J. Hoch, R. Kodet, J. Bartůňková, R. Špíšek, A. Fialová
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Antigens, CD1 biosynthesis MeSH
- Cell Differentiation genetics MeSH
- Early Detection of Cancer MeSH
- Dendritic Cells immunology metabolism pathology MeSH
- Genetic Association Studies MeSH
- GPI-Linked Proteins biosynthesis MeSH
- Carcinoma diagnosis genetics pathology physiopathology MeSH
- Colorectal Neoplasms diagnosis genetics pathology physiopathology MeSH
- Humans MeSH
- Neoplasm Recurrence, Local MeSH
- Cell Adhesion Molecules, Neuronal biosynthesis MeSH
- Mutation genetics MeSH
- DNA Mutational Analysis MeSH
- Biomarkers, Tumor genetics MeSH
- Follow-Up Studies MeSH
- Cell Movement genetics MeSH
- Prognosis MeSH
- Proto-Oncogene Proteins genetics MeSH
- ras Proteins genetics MeSH
- Lymphocytes, Tumor-Infiltrating immunology metabolism pathology MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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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- $a 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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