High-frequency microsatellite instability and BRAF mutation (V600E) in unselected Serbian patients with colorectal cancer
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Microsatellite instability (MSI) is a genetic consequence of a MisMatch Repair defect in colorectal cancer (CRC). We compared clinicopathohistological features with MSI status of CRC and evaluated prognostic significance of MSI status and BRAF mutation in the group of MSI-H tumors. 155 primary CRCs were excised surgically, 2006–2008. MSI analysis was carried out using a fluorescence-based pentaplex polymerase chain reaction technique. BRAF mutation (V600E) was analyzed by direct sequencing in MSI-H tumors. For all patients were evaluated: age, gender, localization, tumor cell type, tumor differentiation, mucin production, lymphocytic infiltration (TILs) and TNM stage. Patients’ disease-free survival (DFS) was compared according to MSI and BRAF status using Kaplan–Meier test. Of the 155 CRCs, 19 (12.3%) were MSI-H, and 136 (87.7%) were MSS/L. BRAF mutations were found in 4 of the MSI-H tumors. Patients with MSI-H CRC had lower recurrence rate (log rank test; P = 0.04) than MSS/L group. Patients with MSI-H tumor and BRAF mutation had worse DFS than MSI-H tumors without this mutation (log rank test; P = 0.01). Most of the clinicopathologic characteristics of MSI-H CRC in Serbian patients are similar to those reported in previous studies. Patients with MSI tumor phenotype had favourable prognosis, but in those with BRAF mutation higher recurrence rate was observed.
KeywordsMicrosatellite instability Colon cancer Clinicopathohistological features BRAF mutation
This work was supported by Ministry of Science; Republic of Serbia: Grant No 41033.
Conflict of interest
The authors declare that they have no conflict of interest.
- Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW et al (1998) A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257PubMedGoogle Scholar
- Carethers JM, Smith EJ, Behling CA et al (2004) Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer mismatch repair proficiency and in vitro response to 5-fluorouracil. Gastroenterology 126:394–401. doi: 10.1053/j.gastro.2003.12.023 PubMedCrossRefGoogle Scholar
- Kazama Y, Watanabe T, Kanazawa T, Tanaka J, Tanaka T, Nagawa H (2008) Poorly differentiated colorectal adenocarcinomas show higher rates of microsatellite instability and promoter methylation of p16 and hMLH1: a study matched for T classification and tumor location. J Surg Oncol 97(3):278–283. doi: 10.1002/jso.20960 PubMedCrossRefGoogle Scholar
- McGivern A, Wynter CV, Whitehall VL, Kambara T, Spring KJ, Walsh MD et al (2004) Promoter hypermethylation frequency and BRAF mutations distinguish hereditary non-polyposis colon cancer from sporadic MSI-H colon cancer. Fam Cancer 3:101–107. doi: 10.1023/B:FAME.0000039861.30651.c8 PubMedCrossRefGoogle Scholar
- Westra J, Schaapveld M, Hollema H et al (2005) Determination of TP53 mutation is more relevant than microsatellite instability status for the prediction of disease-free survival in adjuvant-treated stage III colon cancer patients. J Clin Oncol 23:5635–5643. doi: 10.1200/JCO.2005.04.096 PubMedCrossRefGoogle Scholar
- Yearsley M, Hampel H, Lehman A, Nakagawa H, de la Chapelle A, Frankel WL (2006) Histologic features distinguish microsatellite high from microsatellite-low and microsatellite-stable colorectal carcinomas, but do not differentiate germline mutations from methylation of the MLH1 promoter. Hum Pathol 37:831–838. doi: 10.1016/j.humpath.2006.02.009 PubMedCrossRefGoogle Scholar