Microsatellite instability in colorectal cancer: frequency, clinical and morphological features, role in the choice of treatment
Background. The purpose was to evaluate the frequency, clinical and morphological features of microsatellite instability (MSI) in colorectal cancer (CRC) in the Ukrainian population. Materials and methods. The study included 351 patients with CRC. Two methods were used to diagnose MSI: 1) detection of the instability in the microsatellite loci using polymerase chain reaction; 2) immunohistochemically, by detecting the deficiency of the mismatch repair system proteins (MLH1, MSH2, MSH6, PMS2; Dako). In addition, some patients were tested for KRAS, NRAS and BRAF mutations by realtime polymerase chain reaction. Results. It was shown that the frequency of MSI among Ukrainian patients with CRC was 14.2 %. The frequency of MSIH status was significantly higher in men (25.35 %) than in women (10 %) (P = 0.04). The MSIH status was associated with younger age (P = 0.002) in men. In addition, MSIH CRC was more often associated with special histological types of CRC, inflammatory infiltration and higher rate of BRAF mutation (P = 0.03). Although almost half of the MSIH CRC showed high grade, distant metastases rate was significantly lower comparing with MSI (17.4 vs. 52.9 %, P = 0.001) regardless of gender. Conclusions. Screening of patients with CRC on MSI will allow the identification of additional candidates for immunotherapy in order to improve treatment efficacy and outcomes.
Full Text:PDF (Русский)
Arakawa K., Hata K., Kawai K. et al. Predictors for High Microsatellite Instability in Patients with Colorectal Cancer Fulfilling the Revised Bethesda Guidelines // Anticancer. Res. — 2018. — 38 (8). — 4871-4876. doi: 10.21873/anticanres.12800.
Avendaño-Ortiz J., Casarrubios M., Montalbán-Hernández K. et al. PD-L1/PD-1 crosstalk in colorectal cancer: are we targeting the right cells? // BMC Cancer. — 2018. — 3, 18 (1). — 945. doi: 10.1186/s12885-018-4853-0.
Bhalla A., Zulfiqar M., Bluth M.H. Molecular Diagnostics in Colorectal Carcinoma: Advances and Applications for 2018 // Clin. Lab. Med. — 2018. — 38 (2). — 311-342. doi: 10.1016/j.cll.2018.02.008.
Brenner H., Chen C. The colorectal cancer epidemic: challenges and opportunities for primary, secondary and tertiary prevention // Br. J. Cancer. — 2018. doi: 10.1038/s41416-018-0264-x
Dawood S. The evolving role of immune oncology in colorectal cancer // Chin. Clin. Oncol. — 2018. — 7 (2). — 17. doi: 10.21037/cco.2018.04.07.
Díaz-Tasende J. Colorectal cancer screening and survival // Rev. Esp. Enferm. Dig. — 2018. — 4. — 110. doi: 10.17235/reed.2018.5870/2018.
Dienstmann R., Salazar R., Tabernero J. Molecular Subtypes and the Evolution of Treatment Decisions in Metastatic Colorectal Cancer // Am. Soc. Clin. Oncol. Educ. Book. — 2018. — 23 (38). — 231-238. doi: 10.1200/EDBK_200929.
Fabrizio D.A., George T.J. Jr, Dunne R.F. et al. Beyond microsatellite testing: assessment of tumor mutational burden identifies subsets of colorectal cancer who may respond to immune checkpoint inhibition // J. Gastrointest. Oncol. — 2018. — 9 (4). — 610-617. doi: 10.21037/jgo.2018.05.06.
Gupta R., Sinha S., Paul R.N. The impact of microsatellite stability status in colorectal cancer // Curr. Probl. Cancer. — 2018. — 18. pii: S0147-0272(17)30169-1. doi: 10.1016/j.currproblcancer.2018.06.010.
Nguyen H.T., Duong H.Q. The molecular characteristics of colorectal cancer: Implications for diagnosis and therapy // Oncol. Lett. — 2018. — 16 (1). — 9-18. doi: 10.3892/ol.2018.8679.
Patel S.A., Longacre T.A., Ladabaum U., Lebensohn A., Lin A.Y., Haraldsdottir S. Tumor Molecular Testing Guides Anti-PD-1 Therapy and Provides Evidence for Pathogenicity of Mismatch Repair Variants // Oncologist. — 2018. — 2. pii: theoncologist.2018-0108. doi: 10.1634/theoncologist.2018-0108.
Pearlman R., Markow M., Knight D. et al. Two-stain immunohistochemical screening for Lynch syndrome in colorectal cancer may fail to detect mismatch repair deficiency // Mod. Pathol. — 2018. — 2. doi: 10.1038/s41379-018-0058-y.
Salem M.E., Puccini A., Grothey A. et al. Landscape of Tumor Mutation Load, Mismatch Repair Deficiency, and PD-L1 Expression in a Large Patient Cohort of Gastrointestinal Cancers // Mol. Cancer. Res. — 2018. — 16 (5). — 805-812. doi: 10.1158/1541-7786.MCR-17-0735.
Trabelsi M., Farah F., Blel A., Jaafoura M.H., Kharrat M., Rammeh S. Prognostic values of detecting MSI phenotypes in colorectal carcinoma by immunohistochemical method compared to molecular investigation // Tunis Med. — 2017. — 95 (12). — 229-236.
Van der Jeught K., Xu H.C., Li Y.J., Lu X.B., Ji G. Drug resistance and new therapies in colorectal cancer // World J. Gastroenterol. — 2018. — 14, 24 (34). — 3834-3848. doi: 10.3748/wjg.v24.i34.3834.
Xiao X., Dong D., He W., Song L., Wang Q., Yue J., Xie L. Mismatch repair deficiency is associated with MSI phenotype, increased tumor-infiltrating lymphocytes and PD-L1 expression in immune cells in ovarian cancer // Gynecol. Oncol. — 2018. — 149 (1). — 146-154. doi: 10.1016/j.ygyno.2018.02.009.
Yamamoto H., Imai K. Microsatellite instability: an update // Arch. Toxicol. — 2015. — 89 (6). — 899-921. doi: 10.1007/s00204-015-1474-0.
- There are currently no refbacks.
Copyright (c) 2019 Practical oncology
This work is licensed under a Creative Commons Attribution 4.0 International License.
© Publishing House Zaslavsky, 1997-2020