Bevezetés: A vastagbéldaganatokra jellemző genetikai instabilitás megnyilvánulhat több úton: kromoszomális instabilitás, mikroszatellita-instabilitás, illetve „CpG-island methylator phenotype”. Ezek pontosabb karakterizálásával a rendelkezésre álló kezelések elviekben optimalizálhatók lehetnek. Célkitűzés: A szerzők a mikroszatellita-instabilitás előfordulását, heterogenitását, prognosztikus és prediktív potenciálját vizsgálták 122 primer colontumor szisztematikusan szelektált régióiban és 69 párosított májmetasztázisban. Módszer: Szöveti multiblokkok kialakítása után az MLH1, MSH2, MSH6 és PMS2 kifejeződését vizsgálták immunhisztokémiai módszerrel. Eredmények: A betegek 11,5%-a (14/122) rendelkezett mikroszatellita-instabil fenotípusú daganattal. A különböző tumorrégiók fehérjekifejeződésében nem volt jelentős különbség. A primer tumor–májmetasztázis párok esetében 20,2%-ban a kettő más mismatch repair státusba volt sorolható. A relapsusmentes és teljes túlélést tekintve a mismatch repair státus nem volt prognosztikus. Az 5-fluorouracil-, oxaliplatin-, irinotecan-, bevacizumab-, cetuximab-, panitumumabterápia hatékonyságát tekintve mismatch repair státus nem volt prediktív a progressziómentes és teljes túlélés adatai alapján. Következtetések: A prognosztikus faktorok pontosabb meghatározása nagyobb esetszámú, pontosan szelektált vizsgálat keretében hatékonyabbá teheti a kezelés megválasztását. Orv. Hetil., 2015, 156(36), 1460–1471.
Tusnády, G., Gaudi, I., Rejtő, L., et al.: Survival chances of Hungarian cancer patients in the National Cancer Registry. [A magyar daganatos betegek túlélési esélye a nemzeti rákregiszter adatai alapján.] Magy. Onkol., 2008, 52(4), 339–349. [Hungarian]
Goel, A., Arnold, C. N., Niedzwiecki, D., et al.: Characterization of sporadic colon cancer by patterns of genomic instability. Cancer Res., 2003, 63(7), 1608–1614.
Liefers, G. J., Tollenaar, R. A.: Cancer genetics and their application to individualised medicine. Eur. J. Cancer, 2002, 38(7), 872–879.
Konishi, M., Kikuchi-Yanoshita, R., Tanaka, K., et al.: Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer. Gastroenterology, 1996, 111(2), 307–317.
Aaltonen, L. A., Peltomäki, P., Leach, F. S., et al.: Clues to the pathogenesis of familial colorectal cancer. Science, 1993, 260(5109), 812–816.
Kouraklis, G., Misiakos, E. P.: Hereditary nonpolyposis colorectal cancer (Lynch syndrome): criteria for identification and management. Dig. Dis. Sci., 2005, 50(2), 336–344.
Yamamoto, H., Imai, K.: Microsatellite instability: an update. Arch. Toxicol., 2015, 89(6), 899–921.
Popat, S., Hubner, R., Houlston, R. S.: Systematic review of microsatellite instability and colorectal cancer prognosis. J. Clin. Oncol., 2005, 23(3), 609–618.
Bubb, V. J., Curtis, L. J., Cunningham, C., et al.: Microsatellite instability and the role of hMSH2 in sporadic colorectal cancer. Oncogene, 1996, 12(12), 2641–2649.
Sinicrope, F. A., Foster, N. R., Yoon, H. H., et al.: Association of obesity with DNA mismatch repair status and clinical outcome in patients with stage II or III colon carcinoma participating in NCCTG and NSABP adjuvant chemotherapy trials. J. Clin. Oncol., 2012, 30(4), 406–412.
Cicek, M. S., Lindor, N. M., Gallinger, S., et al.: Quality assessment and correlation of microsatellite instability and immunohistochemical markers among population- and clinic-based colorectal tumors results from the Colon Cancer Family Registry. J. Mol. Diagn., 2011, 13(3), 271–281.
Kim, H., Jen, J., Vogelstein, B., et al.: Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am. J. Pathol., 1994, 145(1), 148–156.
Tejpar, S.: The multidisciplinary management of gastrointestinal cancer. The use of molecular markers in the diagnosis and treatment of colorectal cancer. Best Pract. Res. Clin. Gastroenterol., 2007, 21(6), 1071–1087.
Gafa, R., Maestri, I., Matteuzzi, M., et al.: Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability. Cancer, 2000, 89(10), 2025–2037.
Carethers, J. M., Murali, B., Yang, B., et al.: Influence of race on microsatellite instability and CD8+ T cell infiltration in colon cancer. PLoS ONE, 2014, 9(6), e100461.
Cascinu, S., Georgoulias, V., Kerr, D., et al.: Colorectal cancer in the adjuvant setting: perspectives on treatment and the role of prognostic factors. Ann. Oncol., 2003, 14 (Suppl. 2), ii25–ii29.
Sargent, D. J., Marsoni, S., Monges, G., et al.: Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J. Clin. Oncol., 2010, 28(20), 3219–3226.
Ribic, C. M., Sargent, D. J., Moore, M. J., et al.: Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N. Engl. J. Med., 2003, 349(3), 247–257.
Donada, M., Bonin, S., Barbazza, R., et al.: Management of stage II colon cancer – the use of molecular biomarkers for adjuvant therapy decision. BMC Gastroenterol., 2013, 13, 36.
Boland, C. R., Goel, A.: Microsatellite instability in colorectal cancer. Gastroenterology, 2010, 138(6), 2073–2087. e3.
Lynch, H. T., Lynch, J. F., Lynch, P. M., et al.: Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Fam. Cancer, 2008, 7(1), 27–39.
Lynch, H. T., Smyrk, T. C., Watson, P., et al.: Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology, 1993, 104(5), 1535–1549.
Gryfe, R., Kim, H., Hsieh, E. T., et al.: Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N. Engl. J. Med., 2000, 342(2), 69–77.
Al-Sohaily, S., Biankin, A., Leong, R., et al.: Molecular pathways in colorectal cancer. J. Gastroenterol. Hepatol., 2012, 27(9), 1423–1431.
Abdel-Rahman, W. M., Georgiades, I. B., Curtis, L. J., et al.: Role of BAX mutations in mismatch repair-deficient colorectal carcinogenesis. Oncogene, 1999, 18(12), 2139–2142.
Barnetson, R., Jass, J., Tse, R., et al.: Mutations associated with microsatellite unstable colorectal carcinomas exhibit widespread intratumoral heterogeneity. Genes Chromosomes Cancer, 2000, 29(2), 130–136.
Chung, Y. J., Park, S. W., Song, J. M., et al.: Evidence of genetic progression in human gastric carcinomas with microsatellite instability. Oncogene, 1997, 15(14), 1719–1726.
Ishimaru, G., Adachi, J., Shiseki, M., et al.: Microsatellite instability in primary and metastatic colorectal cancers. Int. J. Cancer, 1995, 64(3), 153–157.
Blaker, H., Graf, M., Rieker, R. J., et al.: Comparison of losses of heterozygosity and replication errors in primary colorectal carcinomas and corresponding liver metastases. J. Pathol., 1999, 188(3), 258–262.
Barnetson, R., Eckstein, R., Robinson, B., et al.: There is no increase in frequency of somatic mutations in metastases compared with primary colorectal carcinomas with microsatellite instability. Genes Chromosomes Cancer, 2003, 38(2), 149–156.
Chen, W. S., Chen, J. Y., Liu, J. M., et al.: Microsatellite instability in sporadic-colon-cancer patients with and without liver metastases. Int. J. Cancer, 1997, 74(4), 470–474.
Chong, J. M., Fukayama, M., Hayashi, Y., et al.: Microsatellite instability in the progression of gastric carcinoma. Cancer Res., 1994, 54(17), 4595–4597.
Merlo, A., Mabry, M., Gabrielson, E., et al.: Frequent microsatellite instability in primary small cell lung cancer. Cancer Res., 1994, 54(8), 2098–2101.
McConechy, M. K., Talhouk, A., Li-Chang, H. H., et al.: Detection of DNA mismatch repair (MMR) deficiencies by immunohistochemistry can effectively diagnose the microsatellite instability (MSI) phenotype in endometrial carcinomas. Gynecol. Oncol., 2015, 137(2), 306–310.
Korphaisarn, K., Pongpaibul, A., Limwongse, C., et al.: Deficient DNA mismatch repair is associated with favorable prognosis in Thai patients with sporadic colorectal cancer. World J. Gastroenterol., 2015, 21(3), 926–934.
Hong, S. P., Min, B. S., Kim, T. I., et al.: The differential impact of microsatellite instability as a marker of prognosis and tumour response between colon cancer and rectal cancer. Eur. J. Cancer, 2012, 48(8), 1235–1243.
Roth, A. D., Delorenzi, M., Tejpar, S., et al.: Integrated analysis of molecular and clinical prognostic factors in stage II/III colon cancer. J. Natl. Cancer Inst., 2012, 104(21), 1635–1646.
Merok, M. A., Ahlquist, T., Røyrvik, E. C., et al.: Microsatellite instability has a positive prognostic impact on stage II colorectal cancer after complete resection: results from a large, consecutive Norwegian series. Ann. Oncol., 2013, 24(5), 1274–1282.
Des Guetz, G., Schischmanoff, O., Nicolas, P., et al.: Does microsatellite instability predict the efficacy of adjuvant chemotherapy in colorectal cancer? A systematic review with meta-analysis. Eur. J. Cancer, 2009, 45(10), 1890–1896.
Elsaleh, H., Joseph, D., Grieu, F., et al.: Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet, 2000, 355(9217), 1745–1750.
Hemminki, A., Mecklin, J. P., Järvinen, H., et al.: Microsatellite instability is a favorable prognostic indicator in patients with colorectal cancer receiving chemotherapy. Gastroenterology, 2000, 119(4), 921–928.
Jover, R., Zapater, P., Castells, A., et al.: The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status. Eur. J. Cancer, 2009, 45(3), 365–373.
Kim, G. P., Colangelo, L. H., Wieand, H. S., et al.: Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute–National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J. Clin. Oncol., 2007, 25(7), 767–772.
Klingbiel, D., Saridaki, Z., Roth, A. D., et al.: Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial. Ann. Oncol., 2015, 26(1), 126–132.
Neumann, J., Reu, S., Kirchner, T.: Prognostic marker profiles for risk of distant metastases in colorectal cancer. Pathologe, 2012, 33(1), 39–44.
Ooki, A., Akagi, K., Yatsuoka, T., et al.: Combined microsatellite instability and BRAF gene status as biomarkers for adjuvant chemotherapy in stage III colorectal cancer. J. Surg. Oncol., 2014, 110(8), 982–988.