Microsatellite instability as a biomarker for PD-1 blockade

Clinical Cancer Research

Volumn 22, Issue 4, 2016, Pages 813-820

  Dudley, Jonathan C ^a   Lin, Ming Tseh ^b   Le, Dung T ^b   Eshleman, James R ^b  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MISMATCH REPAIR PROTEIN PMS2; PROGRAMMED DEATH 1 RECEPTOR; PROTEIN MLH1; PROTEIN MSH2; PROTEIN MSH6; ANTINEOPLASTIC AGENT; PDCD1 PROTEIN, HUMAN; TUMOR MARKER;

BLADDER CANCER; BREAST CANCER; CANCER DIAGNOSIS; CARCINOGENESIS; COLORECTAL CANCER; DIAGNOSTIC APPROACH ROUTE; DNA METHYLATION; ENDOMETRIUM CANCER; ESOPHAGEAL ADENOCARCINOMA; ESOPHAGUS CANCER; EWING SARCOMA; GENE MUTATION; GERM CELL TUMOR; GLIOBLASTOMA; HEAD AND NECK SQUAMOUS CELL CARCINOMA; HEREDITARY NONPOLYPOSIS COLORECTAL CANCER; HUMAN; IMMUNOHISTOCHEMISTRY; KIDNEY CARCINOMA; LIVER CELL CARCINOMA; LUNG CANCER; LYMPHOCYTIC INFILTRATION; MELANOMA; MICROSATELLITE INSTABILITY; OSTEOSARCOMA; OVARY CANCER; PANCREAS ADENOCARCINOMA; POLYMERASE CHAIN REACTION; PRACTICE GUIDELINE; PREDICTION; PRIORITY JOURNAL; PROGNOSIS; PROMOTER REGION; PROSTATE CANCER; REVIEW; SKIN CANCER; SOFT TISSUE SARCOMA; UTERINE CERVIX CANCER; ANTAGONISTS AND INHIBITORS; COLORECTAL NEOPLASMS; GENETICS; MOLECULARLY TARGETED THERAPY; TREATMENT OUTCOME;

ANTINEOPLASTIC AGENTS; BIOMARKERS, TUMOR; COLORECTAL NEOPLASMS; HUMANS; MICROSATELLITE INSTABILITY; MOLECULAR TARGETED THERAPY; PROGNOSIS; PROGRAMMED CELL DEATH 1 RECEPTOR; TREATMENT OUTCOME;

EID: 84964398060     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-15-1678     Document Type: Review

References (100)

1. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366:2455-65.
2. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366:2443-54.
3. Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1 (PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol 2012;24:207-12.
4. Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006;313:1960-4.
5. Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 2005;353:2654-66.
6. Llosa NJ, CruiseM, TamA, Wicks EC, Hechenbleikner EM, Taube JM, etal. The vigorous immune microenvironment ofmicrosatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 2015;5:43-51.
7. Schwitalle Y, Kloor M, Eiermann S, Linnebacher M, Kienle P, Knaebel HP, et al. Immune response against frameshift-induced neopeptides in HNPCC patients and healthy HNPCC mutation carriers. Gastroenterology 2008;134:988-97.
8. LeDT, Uram JN, WangH, Bartlett BR, KemberlingH, EyringAD, etal. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015;372:2509-20.
9. Kelderman S, Schumacher TN, Kvistborg P. Mismatch repair-deficient cancers are targets for anti-PD-1 therapy. Cancer Cell 2015;28:11-3.
10. Roberts SA, Gordenin DA. Hypermutation in human cancer genomes: footprints and mechanisms. Nat Rev Cancer 2014;14:786-800.
11. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, et al. Signatures of mutational processes in human cancer. Nature 2013;500:415-21.
12. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015;348:124-8.
13. SnyderA, MakarovV, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, etal. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 2014;371:2189-99.
14. Yadav M, Jhunjhunwala S, Phung QT, Lupardus P, Tanguay J, Bumbaca S, et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature 2014;515:572-6.
15. Parsons R, Li GM, Longley MJ, Fang WH, Papadopoulos N, Jen J, et al. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell 1993;75:1227-36.
16. Bhattacharyya NP, Skandalis A, Ganesh A, Groden J, Meuth M. Mutator phenotypes in human colorectal carcinoma cell lines. Proc Natl Acad Sci U S A 1994;91:6319-23.
17. Eshleman JR, Lang EZ, Bowerfind GK, Parsons R, Vogelstein B, Willson JK, et al. Increased mutation rate at the hprt locus accompanies microsatellite instability in colon cancer. Oncogene 1995;10:33-7.
18. Modrich P. DNA mismatch correction. Annu Rev Biochem 1987;56:435-66.
19. Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, et al. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 1993;75:1027-38.
20. Liu B, Parsons RE, Hamilton SR, Petersen GM, Lynch HT, Watson P, et al. hMSH2 mutationsinhereditary nonpolyposis colorectal cancer kindreds. Cancer Res 1994;54:4590-4.
21. Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA, etal. Mutation of amutL homologinhereditary colon cancer. Science 1994;263:1625-9.
22. Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK, et al. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature 1994;368:258-61.
23. Eshleman JR, Markowitz SD. Mismatch repair defects in human carcinogenesis. Hum Mol Genet 1996;5:1489-94.
24. Ligtenberg MJ, Kuiper RP, Chan TL, Goossens M, Hebeda KM, Voorendt M, et al. Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 30 exons of TACSTD1. Nat Genet 2009;41:112-7.
25. Markowitz S, Wang J, Myeroff L, Parsons R, Sun L, Lutterbaugh J, et al. Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science 1995;268:1336-8.
26. Umar A, Risinger JI, Hawk ET, Barrett JC. Testing guidelines for hereditary non-polyposis colorectal cancer. Nat Rev Cancer 2004;4:153-8.
27. Cancer Genome Atlas N. Comprehensive molecular characterization of human colon and rectal cancer. Nature 2012;487:330-7.
28. Jung B, Doctolero RT, Tajima A, Nguyen AK, Keku T, Sandler RS, et al. Loss of activin receptor type 2 protein expression in microsatellite unstable colon cancers. Gastroenterology 2004;126:654-9.
29. Funkhouser W K Jr, Lubin IM, Monzon FA, Zehnbauer BA, Evans JP, Ogino S, 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.
30. Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch JF, Lynch PM, et al. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 1993;104:1535-49.
31. Veigl ML, KasturiL, Olechnowicz J, MaAH, LutterbaughJD, Periyasamy S, et al. Biallelic inactivation of hMLH1 by epigenetic gene silencing, a novel mechanism causing human MSI cancers. Proc Natl Acad Sci U S A 1998;95:8698-702.
32. Herman JG, Umar A, Polyak K, Graff JR, Ahuja N, Issa JP, et al. Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc Natl Acad Sci U S A 1998;95:6870-5.
33. Kane MF, Loda M, Gaida GM, Lipman J, Mishra R, Goldman H, et al. Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. Cancer Res 1997;57:808-11.
34. Geurts-Giele WR, Leenen CH, Dubbink HJ, Meijssen IC, Post E, Sleddens HF, et al. Somatic aberrations of mismatch repair genes as a cause of microsatellite-unstable cancers. J Pathol 2014;234:548-59.
35. Kastrinos F, Stoffel EM, Balmana J, Steyerberg EW, Mercado R, Syngal S. Phenotype comparison of MLH1 and MSH2 mutation carriersina cohort of 1, 914 individuals undergoing clinical genetic testing in the United States. Cancer Epidemiol Biomarkers Prev 2008;17:2044-51.
36. Ramsoekh D, Wagner A, van Leerdam ME, Dooijes D, Tops CM, Steyerberg EW, et al. Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management. Hered Cancer Clin Pract 2009;7:17.
37. Talseth-Palmer BA, Wijnen JT, Brenne IS, Jagmohan-Changur S, Barker D, Ashton KA, et al. Combined analysis of three Lynch syndrome cohorts confirms the modifying effects of 8q23.3 and 11q23.1 in MLH1 mutation carriers. Int J Cancer 2013;132:1556-64.
38. Leggett B, Whitehall V. Role of the serrated pathway in colorectal cancer pathogenesis. Gastroenterology 2010;138:2088-100.
39. Eshleman JR, Casey G, Kochera ME, Sedwick WD, Swinler SE, Veigl ML, etal. Chromosome number and structure both aremarkedly stablein RER colorectal cancers and are not destabilizedbymutationofp53. Oncogene 1998;17:719-25.
40. Kim H, Jen J, Vogelstein B, Hamilton SR. Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol 1994;145:148-56.
41. Goldstein J, Tran B, Ensor J, Gibbs P, Wong HL, Wong SF, et al. Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with highlevel microsatellite instability (MSI-H). Ann Oncol 2014;25:1032-8.
42. Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 2005;23:609-18.
43. Lochhead P, Kuchiba A, Imamura Y, Liao X, Yamauchi M, Nishihara R, et al. Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication. J Natl Cancer Inst 2013;105:1151-6.
44. Phipps AI, Limburg PJ, Baron JA, Burnett-Hartman AN, Weisenberger DJ, Laird PW, et al. Association between molecular subtypes of colorectal cancer and patient survival. Gastroenterology 2015;148:77-87.
45. French AJ, Sargent DJ, Burgart LJ, Foster NR, Kabat BF, Goldberg R, et al. Prognostic significance of defective mismatch repair and BRAF V600E in patients with colon cancer. Clin Cancer Res 2008;14:3408-15.
46. Ribic CM, Sargent DJ, Moore MJ, Thibodeau SN, French AJ, Goldberg RM, et al. Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. NEngl JMed 2003;349:247-57.
47. Carethers JM, Smith EJ, Behling CA, Nguyen L, Tajima A, Doctolero RT, et al. Use of 5-fluorouracil and survival in patients with microsatelliteunstable colorectal cancer. Gastroenterology 2004;126:394-401.
48. Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, 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;28:3219-26.
49. Tajima A, Hess MT, Cabrera BL, Kolodner RD, Carethers JM. The mismatch repair complex hMutS alpha recognizes 5-fluorouracil-modified DNA: implications for chemosensitivity and resistance. Gastroenterology 2004;127:1678-84.
50. Tajima A, Iwaizumi M, Tseng-Rogenski S, Cabrera BL, Carethers JM. Both hMutS alpha and hMutS beta DNA mismatch repair complexes participate in 5-fluorouracil cytotoxicity. PLoS One 2011;6:e28117.
51. Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology 2010;138:2073-87.
52. Sinicrope FA, Foster NR, Thibodeau SN, Marsoni S, Monges G, Labianca R, et al. DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst 2011;103:863-75.
53. WebberEM, Kauffman TL, O'Connor E, Goddard KA. Systematic review of the predictive effect of MSI status in colorectal cancer patients undergoing 5FU-based chemotherapy. BMC Cancer 2015;15:156.
54. Vasen HF, Mecklin JP, Khan PM, Lynch HT. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 1991;34:424-5.
55. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. 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 1998;58:5248-57.
56. Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Ruschoff J, et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004;96:261-8.
57. Moreira L, Balaguer F, Lindor N, delaChapelle A, Hampel H, Aaltonen L A, et al. Identification of Lynch syndrome among patients with colorectal cancer. JAMA 2012;308:1555-65.
58. BergKD, Glaser CL, Thompson RE, HamiltonSR, Griffin CA, Eshleman JR. Detection of microsatellite instability by fluorescence multiplex polymerase chain reaction. J Mol Diagn 2000;2:20-8.
59. Bacher JW, Flanagan LA, Smalley RL, Nassif NA, Burgart LJ, Halberg RB, et al. Development of a fluorescent multiplex assay for detection of MSI-High tumors. Dis Markers 2004;20:237-50.
60. Murphy KM, Zhang S, Geiger T, Hafez MJ, Bacher J, Berg KD, et al. Comparison of the microsatellite instability analysis system and the Bethesda panel for the determination of microsatellite instability in colorectal cancers. J Mol Diagn 2006;8:305-11.
61. Ward PM, Dubeau L, Felix J, Kim G, Bacher JW. Comparison between performance of primers for long versus short microsatellite biomarkers in the detection of microsatellite instability due to aberrant MSH6 expression in endometrioid carcinomas [abstract]. In: Proceedings of the Association for Molecular Pathology 2014 Meeting; 2014 Nov. 12-15; National Harbor, MD. Bethesda (MD): AMP; 2014. Abstract nr ST74.
62. Kim TM, Laird PW, Park PJ. The landscape of microsatellite instability in colorectal and endometrial cancer genomes. Cell 2013;155:858-68.
63. Palomaki GE, McClain MR, Melillo S, Hampel HL, Thibodeau SN. EGAPP supplementary evidence review: DNA testing strategies aimed at reducing morbidity and mortality from Lynch syndrome. Genet Med 2009;11:42-65.
64. Ladabaum U, Wang G, Terdiman J, Blanco A, Kuppermann M, Boland CR, et al. Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis. Ann Intern Med 2011;155:69-79.
65. Mvundura M, Grosse SD, Hampel H, Palomaki GE. The cost-effectiveness of genetic testing strategies for Lynch syndrome among newly diagnosed patients with colorectal cancer. Genet Med 2010;12:93-104.
66. Snowsill T, Huxley N, Hoyle M, Jones-Hughes T, Coelho H, Cooper C, et al. A model-based assessment of the cost-utility of strategies to identify Lynch syndrome in early-onset colorectal cancer patients. BMC Cancer 2015;15:313.
67. Mills AM, Liou S, Ford JM, Berek JS, Pai RK, Longacre TA. Lynch syndrome screening should be considered for all patients with newly diagnosed endometrial cancer. Am J Surg Pathol 2014;38:1501-9.
68. Seruca R, Santos NR, David L, Constancia M, Barroca H, Carneiro F, et al. Sporadic gastric carcinomas with microsatellite instability display a particular clinicopathologic profile. Int J Cancer 1995;64:32-6.
69. Orta L, Klimstra DS, Qin J, Mecca P, Tang LH, Busam KJ, 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;33:934-44.
70. MayerF, Gillis AJ, Dinjens W, Oosterhuis JW, BokemeyerC, Looijenga LH. Microsatellite instability of germ cell tumors is associated with resistance to systemic treatment. Cancer Res 2002;62:2758-60.
71. Yamamoto H, Itoh F, Fukushima H, Kaneto H, Sasaki S, Ohmura T, et al. Infrequent widespread microsatellite instability in hepatocellular carcinomas. Int J Oncol 2000;16:543-7.
72. Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 2005;352:1851-60.
73. Zighelboim I, Goodfellow PJ, Gao F, Gibb RK, Powell MA, Rader JS, et al. Microsatellite instability and epigenetic inactivation of MLH1 and outcomeofpatientswith endometrial carcinomasoftheendometrioid type. J Clin Oncol 2007;25:2042-8.
74. Hampel H, Frankel W, Panescu J, Lockman J, Sotamaa K, Fix D, et al. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res 2006;66:7810-7.
75. Cancer Genome Atlas Research N. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014;513:202-9.
76. Chiappini F, Gross-Goupil M, Saffroy R, Azoulay D, Emile JF, Veillhan LA, et al. Microsatellite instability mutator phenotype in hepatocellular carcinoma in non-alcoholic and non-virally infected normal livers. Carcinogenesis 2004;25:541-7.
77. Ruemmele P, Dietmaier W, Terracciano L, Tornillo L, Bataille F, Kaiser A, et al. Histopathologic features and microsatellite instability of cancers of the papilla of vater and their precursor lesions. Am J Surg Pathol 2009;33:691-704.
78. Mitmaker E, Alvarado C, Begin LR, Trifiro M. Microsatellite instability in benign and malignant thyroid neoplasms. J Surg Res 2008;150:40-8.
79. Cesinaro AM, Ubiali A, Sighinolfi P, Trentini GP, Gentili F, Facchetti F. Mismatch repair proteins expression and microsatellite instability in skin lesions with sebaceous differentiation: a study in different clinical subgroups with and without extracutaneous cancer. Am J Dermatopathol 2007;29:351-8.
80. Kruse R, Rutten A, Schweiger N, Jakob E, Mathiak M, Propping P, et al. Frequency of microsatellite instability in unselected sebaceous gland neoplasias and hyperplasias. J Invest Dermatol 2003;120:858-64.
81. Palmieri G, Ascierto PA, Cossu A, Colombino M, Casula M, Botti G, et al. Assessment of genetic instability in melanocytic skin lesions through microsatellite analysis of benign naevi, dysplastic naevi, and primary melanomas and their metastases. Melanoma Res 2003;13:167-70.
82. Murphy MA, Wentzensen N. Frequency of mismatch repair deficiency in ovarian cancer: a systematic review This article is a US Government work and, as such, is in the public domain of the United States of America. Int J Cancer 2011;129:1914-22.
83. Lazo PA. The molecular genetics of cervical carcinoma. Br J Cancer 1999;80:2008-18.
84. Farris AB I I I, Demicco EG, Le LP, Finberg KE, Miller J, Mandal R, et al. Clinicopathologic and molecular profiles of microsatellite unstable Barrett Esophagus-associated adenocarcinoma. AmJSurg Pathol 2011;35:647-55.
85. Kawaguchi K, Oda Y, Takahira T, Saito T, Yamamoto H, Kobayashi C, et al. Microsatellite instability and hMLH1 and hMSH2 expression analysis in soft tissue sarcomas. Oncol Rep 2005;13:241-6.
86. Glavac D, Volavsek M, Potocnik U, Ravnik-Glavac M, Gale N. Low microsatellite instability and high loss of heterozygosity rates indicate dominant role of the suppressor pathway in squamous cell carcinoma of head and neck and loss of heterozygosity of 11q14.3 correlates with tumor grade. Cancer Genet Cytogenet 2003;146:27-32.
87. Hammerschmied C, Stoehr R, Walter B, Denzinger S, Burger M, Blaszyk H, et al. The role of elevated microsatellite alterations at selected tetranucleotides (EMAST) in renal cell carcinoma (RCC). Cancer Res 2007;67:1934.
88. Alldinger I, Schaefer KL, Goedde D, Ottaviano L, Dirksen U, Ranft A, et al. Microsatellite instability in Ewing tumor is not associated with loss of mismatch repair protein expression. J Cancer Res Clin Oncol 2007;133:749-59.
89. ReuschenbachM, Sommerer C, HartschuhW, ZeierM, DoeberitzM, Kloor M. Absence of mismatch repair deficiency-related microsatellite instability in non-melanoma skin cancer. J Invest Dermatol 2012;132:491-3.
90. Burger M, Denzinger S, Hammerschmied CG, Tannapfel A, Obermann EC, Wieland WF, et al. Elevated microsatellite alterations at selected tetranucleotides (EMAST) and mismatch repair gene expression in prostate cancer. J Mol Med (Berl) 2006;84:833-41.
91. Okuda T, Kawakami K, Ishiguro K, Oda M, Omura K, Watanabe G. The profile of hMLH1 methylation and microsatellite instability in colorectal and non-small cell lung cancer. Int J Mol Med 2005;15:85-90.
92. Ninomiya H, Nomura K, Satoh Y, Okumura S, Nakagawa K, Fujiwara M, et al. Genetic instability in lung cancer: concurrent analysis of chromosomal, mini- and microsatellite instability and loss of heterozygosity. Br J Cancer 2006;94:1485-91.
93. Entz-Werle N, Marcellin L, Gaub MP, Guerin E, SchneiderA, Berard-Marec P, et al. Prognostic significance of allelic imbalance at the c-kit gene locus and c-kit overexpression by immunohistochemistry in pediatric osteosarcomas. J Clin Oncol 2005;23:2248-55.
94. Martinez R, Schackert HK, Appelt H, Plaschke J, Baretton G, Schackert G. Low-level microsatellite instability phenotype in sporadic glioblastoma multiforme. J Cancer Res Clin Oncol 2005;131:87-93.
95. Laghi L, Beghelli S, Spinelli A, Bianchi P, Basso G, Di Caro G, et al. Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma. PLoS One 2012;7:e46002.
96. Anbazhagan R, Fujii H, Gabrielson E. Microsatellite instability is uncommon in breast cancer. Clin Cancer Res 1999;5:839-44.
97. Adem C, Soderberg CL, Cunningham JM, Reynolds C, Sebo TJ, Thibodeau SN, et al. Microsatellite instability in hereditary and sporadic breast cancers. Int J Cancer 2003;107:580-2.
98. Kuligina E, Grigoriev MY, Suspitsin EN, Buslov KG, Zaitseva OA, Yatsuk OS, et al. Microsatellite instability analysis of bilateral breast tumors suggests treatment-related origin of some contralateral malignancies. J Cancer Res Clin Oncol 2007;133:57-64.
99. Toyama T, Iwase H, Yamashita H, Iwata H, Yamashita T, Ito K, et al. Microsatellite instability in sporadic human breast cancers. Int J Cancer 1996;68:447-51.
100. Catto JW, Xinarianos G, Burton JL, Meuth M, Hamdy FC. Differential expressionofhMLH1 and hMSH2is related tobladder cancer grade, stage and prognosis but not microsatellite instability. Int J Cancer 2003;105:484-90.