title: Tumor-infiltrating lymphocytes and dendritic cells in human colorectal cancer: their relationship to KRAS mutational status and disease recurrence.
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.
authors: Department of Immunology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, V Úvalu 84, 15006 Prague 5, Czech Republic.
authors: Petr
authors: P
authors: Kocián
authors: Monika
authors: M
authors: Šedivcová
authors: Jan
authors: J
authors: Drgáč
authors: Kateřina
authors: K
authors: Cerná
authors: Jiří
authors: J
authors: Hoch
authors: Roman
authors: R
authors: Kodet
authors: Jiřina
authors: J
authors: Bartůňková
authors: Radek
authors: R
authors: Špíšek
authors: Anna
authors: A
authors: Fialová
mesh_terms: D018949:Antigens, CD1 / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000235:genetics; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D004252:DNA Mutational Analysis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D056726:Genetic Association Studies; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D018949:Antigens, CD1; D014408:Biomarkers, Tumor; C419393:CD1a antigen; D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; C117307:KRAS protein, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C095362:limbic system-associated membrane protein; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins