Actualización en inestabilidad de microsatélitesbiomarcador predictivo de respuesta a inmunoterapia

  1. Irene Ruiz Adelantado
  2. Clara Sáez Ibarra
  3. Laura Noguera Alonso
  4. Lorenzo Alarcón García
Revista:
Revista Sanitaria de Investigación

ISSN: 2660-7085

Ano de publicación: 2024

Volume: 5

Número: 5

Tipo: Artigo

DIALNET GOOGLE SCHOLAR lock_openAcceso aberto editor

Outras publicacións en: Revista Sanitaria de Investigación

Resumo

Microsatellite instability (MSI) represents a pattern of hypermutability occurring in DNA areas called microsatellites, which due to their repetitive nature are highly susceptible to errors caused by disruptions in DNA repair systems, specifically defects in the mismatch repair (MMR) system. These alterations are well-described in tumors included in the spectrum of Lynch Syndrome. It has been observed that patients with microsatellite instability, being in a state of hypermutability, express a greater number of neoantigens, rendering them susceptible to immunotherapy treatments. Approvals have recently been granted for the treatment of patients with microsatellite instability regardless of tumor type or location (agnostic therapy), although despite this, there is no consensus on when it is necessary to study it. Studies and guidelines recommend screening with immunohistochemistry of the 4 MMR system proteins and polymerase chain reaction (PCR) of microsatellites, as aberrant results have been described in up to 10% of cases. Next-generation sequencing (NGS) of MMR system protein genes is the most accurate detection method, but its low availability in healthcare centers relegates it to a method relegated to research. Regarding immunotherapy, a universal determination is not established, and individualized studies are recommended for cases refractory to conventional treatment. Studies reported in the literature use different detection methods, with variable cutoff points, which hinders standardization, interpretation, and reproducibility.

Referencias bibliográficas

  • Kawakami H, Zaanan A, Sinicrope FA. Implications of mismatch repair-deficient status on management of early-stage colorectal cancer. J Gastrointest Oncol 2015; 6: 676-684.
  • Richman S. Deficient mismatch repair: Read all about it (Review). Int Oncol 2015; 47:1189-1202.
  • Baretti M, Le DT. DNA mismatch repair in cancer. Pharmacol Ther 2018; 189: 45–62.
  • Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, Gevafb R, Gottfried M, Penel N, Hansen AR, Piha-Paul SA, Doi T, Gao B, Chung HC, Lopez-Martin J, Bang YJ, Frommer RS, Shah M, Ghori R, Joe AK, Pruitt SK, Diaz LA Jr. Efficacy of Pembrolizumab in Patients with Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study. J Clin Oncol. 2020 Jan 1;38(1):1-10.
  • Luchini C, Bibeau F, Ligtenberg MJL, Singh N, Nottegar A, Bosse T, Miller R, Riaz N, Douillard JY, Andre F, Scarpa A. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol. 2019 Aug 1;30(8):1232-1243.
  • Beghelli S, de Manzoni G, Barbi S, et al. Microsatellite instability in gastric cancer is associated with better prognosis in only stage II cancers. Surgery 2006; 139: 347-356.
  • Funkhouser WK, Jr., Lubin IM, Monzon FA, et al. Relevance, pathogenesis, and testing algorithm for mismatch repair-defective colorectal carcinomas: a report of the association for molecular pathology. J Mol Diagn 2012; 14: 91-103.
  • Lindor NM, Burgart LJ, Leontovich O, et al. Immunohistochemistry versus microsatellite instability testing in phenotyping colorectal tumors. J Clin Oncol 2002; 20: 1043-1048.
  • Engel KB, Moore HM. Effects of preanalytical variables on the detection of proteins by immunohistochemistry in formalin-fixed, paraffin- embedded tissue. Arch Pathol Lab Med 2011; 135: 537–543.
  • Rodriguez-Bigas MA, Boland CR, Hamilton SR et al. A National Cancer Institute Workshop on hereditary nonpolyposis colorectal cancer syndrome: meeting highlights and Bethesda guidelines. J Natl Cancer Inst 1997; 89(23): 1758–1762.
  • Goel A, Nagasaka T, Hamelin R, Boland CR. An optimized pentaplex PCR for detecting DNA mismatch repair-deficient colorectal cancers. PLoS One 2010; 5(2): e9393.
  • Umar A, Boland CR, Terdiman JP et al. Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004; 96(4): 261–268.
  • Hause RJ, Pritchard CC, Shendure J, Salipante SJ. Classification and characterization of microsatellite instability across 18 cancer types. Nat Med 2016; 22(11): 1342–1350.
  • Nowak JA, Yurgelun MB, Bruce JL et al. Detection of mismatch repair deficiency and microsatellite instability in colorectal adenocarcinoma by targeted next-generation sequencing. J Mol Diagn 2017; 19(1): 84–91.
  • Muller CI, Schulmann K, Reinacher-Schick A, et al. Predictive and prognostic value of microsatellite instability in patients with advanced colorectal cancer treated with a fluoropyrimidine and oxaliplatin containing first-line chemotherapy. A report of the AIO Colorectal Study Group. Int J Colorectal Dis 2008; 23: 1033-1039.
  • Dudley JC, Lin MT, Le DT, et al. Microsatellite Instability as a Biomarker for PD-1 Blockade. Clin Cancer Res 2016; 22: 813-820.
  • Le DT, Uram JN, Wang H, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015; 372: 2509-2520.
  • Kelderman S, Schumacher TN, Kvistborg P. Mismatch Repair-Deficient Cancers Are Targets for Anti-PD-1 Therapy. Cancer Cell 2015; 28: 11-13.
  • Imai K, Yamamoto H. Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 2008; 29: 673-680.
  • Lynch PM. The Case for Universal Testing of Colorectal Tumors for Microsatellite Instability: A Coming Mismatch Between Clinical and Laboratory Testing. Dig Dis Sci 2015; 60: 2225-2227.
  • Ligtenberg MJ, Kuiper RP, Chan TL, et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3′ exons of TACSTD1. Nat Genet 2009; 41: 112-117.
  • Durno CA, Sherman PM, Aronson M, et al. Phenotypic and genotypic characterisation of biallelic mismatch repair deficiency (BMMR-D) syndrome. Eur J Cancer 2015; 51: 977-983.
  • Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357(6349):409-13.
  • Gargiulo P, Della Pepa C, Berardi S, et al. Tumor genotype and immune microenvironment in POLE-ultramutated and MSI-hypermutated Endometrial Cancers: New candidates for checkpoint blockade immunotherapy? Cancer Treat Rev 2016; 48: 61-68.
  • Setaffy L, Langner C. Microsatellite instability in colorectal cancer: clinicopathological significance. Pol J Pathol 2015; 66: 203-218.
  • Sargent DJ, 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: 3219-3226.
  • Marrelli D, Polom K, Pascale V, et al. Strong Prognostic Value of Microsatellite Instability in Intestinal Type Non-cardia Gastric Cancer. Ann Surg Oncol 2016; 23: 943-950.
  • Giampieri R, Maccaroni E, Mandolesi A, et al. Mismatch repair deficiency may affect clinical outcome through immune response activation in metastatic gastric cancer patients receiving first-line chemotherapy. Gastric Cancer 2016.
  • Bockorny B, Pectasides E. The emerging role of immunotherapy in gastric and esophageal adenocarcinoma. Future Oncol 2016.
  • Jou E, Rajdev L. Current and emerging therapies in unresectable and recurrent gastric cancer. World J Gastroenterol 2016; 22: 4812-4823.
  • Gingras MC, Covington KR, Chang DK et al. Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation. Cell Rep 2016; 14: 907-919.
  • Yachida S, Wood LD, Suzuki M, et al. Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma. Cancer Cell 2016; 29: 229-240.
  • Gingras MC, Covington KR, Chang DK et al. Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation. Cell Rep 2016; 14: 907-919.
  • Yachida S, Wood LD, Suzuki M, et al. Genomic Sequencing Identifies ELF3 as a Driver of Ampullary Carcinoma. Cancer Cell 2016; 29: 229-240.
  • Bockorny B, Pectasides E. The emerging role of immunotherapy in gastric and esophageal adenocarcinoma. Future Oncol 2016.
  • Roa SJ, Martinez SR, Montenegro S, et al. [Microsatellite instability and human papilloma virus genotypes in preneoplastic and neoplastic uterine cervix lesions]. Rev Med Chil 2007; 135: 37-44.
  • Orta L, Klimstra DS, Qin J, et al. Towards identification of hereditary DNA mismatch repair deficiency: sebaceous neoplasm warrants routine immunohistochemical screening regardless of patient’s age or other clinical characteristics. Am J Surg Pathol 2009; 33: 934-944.
  • Martinez R, Schackert HK, Plaschke J, et al. Molecular mechanisms associated with chromosomal and microsatellite instability in sporadic glioblastoma multiforme. Oncology 2004; 66: 395-403.
  • Alonso M, Hamelin R, Kim M, et al. Microsatellite instability occurs in distinct subtypes of pediatric but not adult central nervous system tumors. Cancer Res 2001; 61: 2124-2128.
  • Eckert A, Kloor M, Giersch A, et al. Microsatellite instability in pediatric and adult high-grade gliomas. Brain Pathol 2007; 17: 146-150.
  • Viana-Pereira M, Lee A, Popov S, et al. Microsatellite instability in pediatric high grade glioma is associated with genomic profile and differential target gene inactivation. PLoS One 2011; 6: e20588.
  • Beltran H. DNA mismatch repair in prostate cancer. J Clin Oncol 2013; 31: 1782-1784.
  • Haraldsdottir S, Hampel H, Wei L, et al. Prostate cancer incidence in males with Lynch syndrome. Genet Med 2014; 16: 553-557.
  • Abida W, Cheng ML, Armenia J, Middha S, Autio KA, Vargas HA, Rathkopf D, Morris MJ, Danila DC, Slovin SF, Carbone E, Barnett ES, Hullings M, Hechtman JF, Zehir A, Shia J, Jonsson P, Stadler ZK, Srinivasan P, Laudone VP, Reuter V, Wolchok JD, Socci ND, Taylor BS, Berger MF, Kantoff PW, Sawyers CL, Schultz N, Solit DB, Gopalan A, Scher HI. Analysis of the Prevalence of Microsatellite Instability in Prostate Cancer and Response to Immune Checkpoint Blockade. JAMA Oncol. 2019 Apr 1;5(4):471-478.
  • Bonneville, R., Krook, M. A., Kautto, E. A., Miya, J., Wing, M. R., Chen, H. Z., Reeser, J. W., Yu, L., & Roychowdhury, S. (2017). Landscape of Microsatellite Instability across 39 Cancer Types. JCO precision oncology, 2017, PO.17.00073.
  • Gubin MM, Zhang X, Schuster H, et al. Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 2014; 515: 577-581.
  • Llosa NJ, Cruise M, Tam A, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 2015; 5: 43-51.
  • Lenz HJ, Van Cutsem E, Luisa Limon M, Wong KYM, Hendlisz A, Aglietta M, García-Alfonso P, Neyns B, Luppi G, Cardin DB, Dragovich T, Shah U, Abdullaev S, Gricar J, Ledeine JM, Overman MJ, Lonardi S. First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study. J Clin Oncol. 2022 Jan 10;40(2):161-170.
  • Lemery S, Keegan P, Pazdur R. First FDA Approval Agnostic of Cancer Site — When a Biomarker Defines the Indication. N Engl J Med. 2017;377(15):1409-12.
  • Marcus L, Lemery SJ, Keegan P, Pazdur R. FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors. Clin Cancer Res. 2019 Jul 1;25(13):3753-3758. doi: 10.1158/1078-0432.CCR-18-4070. Epub 2019 Feb 20.
  • Bristol Myers Squibb receives European Commission approval for Opdivo (nivolumab) plus Yervoy (ipilimumab) for the treatment of mismatch repair deficient or microsatellite instability–high metastatic colorectal cancer after prior chemotherapy. News release. Bristol Myers Squibb. June 29, 2021. Accessed June 29, 2021.
  • European Commission approves Merck’s KEYTRUDA® (pembrolizumab) for patients with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors in five different types of cancer. News release. Merck. April 29, 2022.
  • European Commission approves KEYTRUDA (pembrolizumab) as first-line treatment in adult patients with metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer. News release. Merck. January 26, 2021.
  • Viale G, Trapani D, Curigliano G. Mismatch Repair Deficiency as a Predictive Biomarker for Immunotherapy Efficacy. BioMed Res Int. 2017;2017:1-7.
Fonte de datos: Dialnet