title: Coexistence of MSI with KRAS mutation is associated with worse prognosis in colorectal cancer.
abstract: Kristen rat sarcoma viral oncogene homolog (KRAS) and microsatellite instability (MSI) are prognostic markers of colorectal cancer (CRC). However, the clinical value is still not fully understood, when giving the consideration to both the molecular makers. Five hundred fifty-one patients with CRC were retrospectively assessed by determining their clinicopathological features. KRAS mutations were detected by polymerase chain reaction. MSI, a defect in the mismatch repair (MMR) system, was detected by immunohistochemistry. The prognostic value of KRAS in combination with MSI was studied. Among 551 CRC patients, mutations in KRAS codon 12 and KRAS codon 13 were detected in 34.5% and 10.5% of patients, respectively. Four hundred one tumors were randomly selected to detect for MMR proteins expression. In this analysis, 30 (7.5%) tumors that had at least 1 MMR protein loss were defined as MMR protein-deficient (MMR-D), and the remaining tumors were classed as MMR protein-intact (MMR-I). According to KRAS mutation and MSI status, CRC was classified into 4 groups: Group 1, KRAS-mutated and MMR-I; Group 2, KRAS-mutated and MMR-D; Group 3, KRAS wild and MMR-I; and Group 4, KRAS wild and MMR-D. We found that patients in Group4 had the best prognosis. In conclusion, combination status of KRAS and MSI status may be used as a prognostic biomarker for CRC patient, if validated by larger studies.
authors.affiliation: The Comprehensive Cancer Center, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University Department of Pathology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.forename: Wen-Yue
authors.initials: WY
authors.lastname: Yan
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Lei
authors.initials: L
authors.lastname: Cheng
authors.forename: Mi
authors.initials: M
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jiong
authors.initials: J
authors.lastname: Shi
authors.forename: Bao-Rui
authors.initials: BR
authors.lastname: Liu
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Qian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D012189:Retrospective Studies; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)