ABSTRACT
KRAS and BRAF mutations are well-recognized molecular alterations during colorectal carcinogenesis, but there is little agreement on their effect on tumor characteristics. Therefore, we aimed to evaluate the distribution of the most common KRAS and BRAF mutations in Greek patients with colorectal cancer and their possible associations with clinical histopathological parameters. In this study, 322 and 188 colorectal carcinomas were used for the mutation analysis of KRAS (exon 2) and BRAF (exon 15) genes, respectively. The mutational status of both genes was evaluated by polymerase chain reaction and sequencing analysis. Although the overall frequency of KRAS mutations (36.6%) seemed to be similar to those reported for other populations, the rate of point mutations at codon 13 was significantly lower (12%) in Greek patients with colorectal cancer and associated with male gender (P < 0.05). Tumors with G>T codon 12 transversions and G>C transitions showed more frequent lymph node metastasis (P < 0.05, P < 0.005, respectively). The rate of KRAS mutations gradually decreased with increasing histological grade (P < 0.05), as opposed to BRAF mutations, which were strongly associated with poorly differentiated tumors (P < 0.005). Additionally, we found that the histological features of preexisting adenoma were associated with the absence of BRAF mutations, in contrast to KRAS (P < 0.05). Our data suggested that there seems to be a correlation between morphological criteria and discrete genetic pathways in colorectal carcinogenesis. Moreover, ethnic or geographic factors may have an impact on genetic background of colorectal carcinomas, and specific types of KRAS mutations may influence the metastatic potential of colorectal tumors.
Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Mutation , Proto-Oncogene Proteins B-raf/genetics , ras Proteins/genetics , Amino Acid Substitution , Codon , DNA Mutational Analysis , Exons , Female , Humans , Male , Neoplasm Grading , Neoplasm Staging , Point Mutation , PrognosisABSTRACT
OBJECTIVE: Cancer patients usually develop malnutrition which may alter their innate immune system integrity. The aim of this study was to investigate the clinical relevance of chemokine response after lipopolysaccharide (LPS)-stimulation in metastatic non-small cell lung cancer (NSCLC). METHODS: Blood samples from metastatic NSCLC patients were incubated with LPS before the onset of systemic therapy. Interleukin (IL)-6 and IL-8 levels at baseline and after LPS-stimulation were measured and the fold change compared to baseline levels was evaluated as the stimulation index for each cytokine per patient. Results were correlated with sex, age, smoking status, histologic subtype, performance status (PS), albumin, Mini Nutritional Assessment (MNA) status and clinical outcomes. RESULTS: Totally 103 patients were evaluated. Mean (±SD) stimulation index was 37.6 (±57.8) for IL-6 and 76.7 (±133.4) for IL-8. The disease control rate after first-line chemotherapy was 44/80 (55 %) and the mean (±SD) progression-free survival (PFS) and overall survival (OS) were 4.2 (±3.9) and 9.2 (±1.1) months, respectively. MNA, PS, albumin, IL-6 and IL-8 stimulation indices were univariately associated with PFS and OS. IL-8 stimulation index emerged as an independent predictor of both PFS and OS, along with PS, and albumin levels. CONCLUSION: The extent of IL-6 and IL-8 stimulation after ex vivo induction with LPS is an important predictor of clinical outcome in metastatic NSCLC patients.