別添文献

2000 年以降にPubMed に報告された、MSI 検査またはIHC 検査によりdMMR と診断された固形がんの頻度をまとめると下記表のようになる。

表. MSI検査またはIHC検査によるdMMR固形がんの種類別頻度

  頻度 Stage IVにおける頻度 アジア諸国における頻度
子宮内膜がん 11-35% 11-19% 29%
胃がん 0-50% 0-18% 8–50%
結腸・直腸がん 4-42% 3.5-5% 1.9-6%
食道がん 0-14% N.R. N.R.
卵巣がん serous3-13%
mucinous: 4-22%
endometrial:4–27%
clear cell:0–14%
N.R. N.R.
乳がん 0–20% N.R. N.R.
頭蓋内腫瘍 0-43% N.R. N.R.
膵がん 0–22% N.R. 13–17%
胆道がん 0–88% 10% 3–41%
小腸がん 9–100% 20% 25–45%
前立腺がん 1–8% N.R. N.R.
尿路上皮がん 3–35% N.R. N.R.
脂腺系腫瘍 40-60% N.R. N.R.

N.R.: not reported

子宮内膜がん 検査法 症例数 Stage dMMR頻度
Matthews KS et al. 2008 IHC 61 (50歳未満のみ) I-IV 34%
Huang HN et al.2015* MSI/IHC 42 N.R. 29%
    19(卵巣・子宮内膜がん合併) N.R. 21%
Ruiz I et al. 2014 IHC 212 I-IV 30%
Egoavil C et al. 2013 MSI/IHC 173 I-IV 35%
Nelson GS et al. 2013 IHC 102 I-IV 28%
Stelloo E et al. 2015 IHC 86 I-IV 15%
  MSI 86 I-IV 22%
Peterson LM et al. 2012 MSI 94 N.R. 31%
  IHC 95 N.R. 25%
Steinbakk A et al. 2011 MSI 273 I-IV 14%
Mackay HJ et al. 2010 MSI 84 I/II 27%
    82 III/IV 11%
Nout RA et al. 2012 MSI/IHC 64 IV 19%
1)
Matthews KS, Estes JM, Conner MG et al. Lynch syndrome in women less than 50 years of age with endometrial cancer. Obstet Gynecol. 2008; 111(5): 1161-1166.
2)
Huang HN, Lin MC, Tseng LH et al. Ovarian and endometrial endometrioid adenocarcinomas have distinct profiles of microsatellite instability, PTEN expression, and ARID1A expression. Histopathology. 2015; 66(4): 517-528.
3)
Ruiz I, Martín-Arruti M, Lopez-Lopez E et al. Lack of association between deficient mismatch repair expression and outcome in endometrial carcinomas of the endometrioid type. Gynecol Oncol. 2014; 134(1): 20-23.
4)
Egoavil C, Alenda C, Castillejo A et al. Prevalence of Lynch syndrome among patients with newly diagnosed endometrial cancers. PLoS One. 2013; 8(11): e79737.
5)
Nelson GS, Pink A, Lee S et al. MMR deficiency is common in high-grade endometrioid carcinomas and is associated with an unfavorable outcome. Gynecol Oncol. 2013; 131(2): 309-314.
6)
Stelloo E, Bosse T, Nout RA et al. Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative. Mod Pathol. 2015; 28(6): 836-844.
7)
Peterson LM, Kipp BR, Halling KC et al. Molecular characterization of endometrial cancer: a correlative study assessing microsatellite instability, MLH1 hypermethylation, DNA mismatch repair protein expression, and PTEN, PIK3CA, KRAS, and BRAF mutation analysis. Int J Gynecol Pathol. 2012; 31(3): 195-205.
8)
Steinbakk A, Malpica A, Slewa A et al. High frequency microsatellite instability has a prognostic value in endometrial endometrioid adenocarcinoma, but only in FIGO stage 1 cases. Cell Oncol (Dordr). 2011; 34(5): 457-465.
9)
Mackay HJ, Gallinger S, Tsao MS et al. Prognostic value of microsatellite instability (MSI) and PTEN expression in women with endometrial cancer: results from studies of the NCIC Clinical Trials Group (NCIC CTG). Eur J Cancer. 2010; 46(8): 1365-1373.
10)
Nout RA, Bosse T, Creutzberg CL et al. Improved risk assessment of endometrial cancer by combined analysis of MSI, PI3K-AKT, Wnt/β-catenin and P53 pathway activation. Gynecol Oncol. 2012; 126(3): 466-473.
胃がん 検査法 症例数 Stage dMMR頻度
Arai T et al. 2013* MSI 464 I-IV 17.7%
Mathiak M et al. 2017 MSI/IHC 452 I-IV 7.5%
Seo HM et al. 2009* I/IHC 292 I-IV 9.2%
Lee HS et al. 2002* MSI/IHC 327 I-IV 9.5%
(StageIII-IVでは4.2%)
Kim KJ et al. 2013* MSI/IHC 1178 I-IV 8.7%
An JY et al. 2012* MSI 1990 I-IV 8.5%
Hayashi T et al. 2006* MSI/IHC 103 (胃がんと大腸がんのdouble primary症例) N.R. 23%
Fang WL et al. 2012* MSI 214 I-III 11.7%
Huang YQ et al. 2010* MSI 288 I-IV 8.0%
Corso G et al. 2009 MSI 250 N.R. 25.2%
Beghelli S et al. 2006 MSI/IHC 510 II 16.3%
Falchetti M et al. 2008 MSI/IHC 159 T1-4 17.0%
Leite M et al. 2011 MSI/IHC 381
29 (家族性)
N.R. 23.1%
24.1%
Bacani J et al. 2005 MSI/IHC 139 I-IV 5.0%
Bevilacqua RA et al. 2000 MSI 42 I-IV 19.0%
van Grieken NC et al. 2013 MSI/IHC 278 (UK)
230 (日本)
204 (シンガポール)
N.R.
II/III
N.R.
9.5%
9.1%
13.9%
Schneider BG et al. 2000 MSI 169 I-IV 17.2%
Gylling A et al. 2007 MSI/IHC 46
15 (リンチ症候群)
I-IV 21.7%
86.7%
An C et al. 2005* MSI 81 N.R. 18.5%
Carvalho R et al. 2004 MSI/IHC 40 N.R. 0%
Chang MS et al. 2003* MSI 549 T1-4 9.7%
Choe WH et al. 2005* MSI/IHC 28 I-IV 50%
(StageIVのみでは0%)
Ferrasi AC et al. 2010 MSI 86 I-IV 16.3%
Grogg KL et al. 2003 IHC 110 I-IV 17%
Kim H et al. 2011* MSI 1786 I-IV 9%
Kim KM et al. 2003* MSI 116 I-IV 14%
Lee HJ et al. 2013* IHC 156 I-IV 10.9%
Lü BJ et al. 2004* MSI 17 (髄様がん) N.R. 41.2%
Mizoshita T et al. 2005* MSI/IHC 70 Advanced 18.6%
Oki E et al. 2009* MSI 240 I-IV 9.4%
(StageIII/IVのみ7.9%)
Solcia E et al. 2009 MSI 294 I-IV 13.9%
Sugai T et al. 2004* MSI 62 I-II 9.7%
Wu M et al. 2004* MSI 62 I-IV 23%
Kim SY et al. 2015* MSI 1276 II/III 8.2%
Choi YY et al. 2011* MSI/IHC 5438 I-IV 13%
Cristescu R et al. 2015* MSI/IHC 300 I-IV 22.7%
(StageIVのみで13.2%)
1)
Arai T, Sakurai U, Sawabe M et al. Frequent microsatellite instability in papillary and solid-type, poorly differentiated adenocarcinomas of the stomach. Gastric Cancer. 2013; 16(4): 505-512.
2)
Mathiak M, Warneke VS, Behrens HM et al. Clinicopathologic Characteristics of Microsatellite Instable Gastric Carcinomas Revisited: Urgent Need for Standardization. Appl Immunohistochem Mol Morphol. 2017; 25(1): 12-24.
3)
Seo HM, Chang YS, Joo SH et al. Clinicopathologic characteristics and outcomes of gastric cancers with the MSI-H phenotype. J Surg Oncol. 2009; 99(3): 143-147.
4)
Lee HS, Choi SI, Lee HK et al. Distinct clinical features and outcomes of gastric cancers with microsatellite instability. Mod Pathol. 2002; 15(6): 632-640.
5)
Kim KJ, Lee TH, Cho NY et al. Differential clinicopathologic features in microsatellite-unstable gastric cancers with and without MLH1 methylation. Hum Pathol. 2013; 44(6): 1055-1064.
6)
An JY, Kim H, Cheong JH et al. Microsatellite instability in sporadic gastric cancer: its prognostic role and guidance for 5-FU based chemotherapy after R0 resection. Int J Cancer. 2012; 131(2): 505-511.
7)
Hayashi T, Arai M, Ueno M et al. Frequency of immunohistochemical loss of mismatch repair protein in double primary cancers of the colorectum and stomach in Japan. Dis Colon Rectum. 2006; 49(10 Suppl): S23-29.
8)
Fang WL, Chang SC, Lan YT et al. Microsatellite instability is associated with a better prognosis for gastric cancer patients after curative surgery. World J Surg. 2012; 36(9): 2131-2138.
9)
Huang YQ, Yuan Y, Ge WT et al. Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients. J Zhejiang Univ Sci B. 2010; 11(9): 647-653.
10)
Corso G, Pedrazzani C, Marrelli D et al. Correlation of microsatellite instability at multiple loci with long-term survival in advanced gastric carcinoma. Arch Surg. 2009; 144(8): 722-727.
11)
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(3): 347-356.
12)
Falchetti M, Saieva C, Lupi R et al. Gastric cancer with high-level microsatellite instability: target gene mutations, clinicopathologic features, and long-term survival. Hum Pathol. 2008; 39(6): 925-932.
13)
Leite M, Corso G, Sousa S et al. MSI phenotype and MMR alterations in familial and sporadic gastric cancer. Int J Cancer. 2011; 128(7): 1606-1613.
14)
Bacani J, Zwingerman R, Di Nicola N et al. Tumor microsatellite instability in early onset gastric cancer. J Mol Diagn. 2005; 7(4): 465-477.
15)
Bevilacqua RA, Simpson AJ. Methylation of the hMLH1 promoter but no hMLH1 mutations in sporadic gastric carcinomas with high-level microsatellite instability. Int J Cancer. 2000; 87(2): 200-203.
16)
van Grieken NC, Aoyama T, Chambers PA et al. KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study. Br J Cancer. 2013; 108(7): 1495-1501.
17)
Schneider BG, Bravo JC, Roa JC et al. Microsatellite instability, prognosis and metastasis in gastric cancers from a low-risk population. Int J Cancer. 2000; 89(5): 444-452.
18)
Gylling A, Abdel-Rahman WM, Juhola M et al. Is gastric cancer part of the tumour spectrum of hereditary non-polyposis colorectal cancer? A molecular genetic study. Gut. 2007; 56(7): 926-933.
19)
An C, Choi IS, Yao JC et al. Prognostic significance of CpG island methylator phenotype and microsatellite instability in gastric carcinoma. Clin Cancer Res. 2005; 11: 656-663.
20)
Carvalho R, Milne AN, van Rees BP et al. Early-onset gastric carcinomas display molecular characteristics distinct from gastric carcinomas occurring at a later age. J Pathol. 2004; 204(1): 75-83.
21)
Chang MS, Lee HS, Kim HS et al. Epstein-Barr virus and microsatellite instability in gastric carcinogenesis. J Pathol. 2003; 199(4): 447-452.
22)
Choe WH, Lee SY, Lee JH et al. High frequency of microsatellite instability in intestinal-type gastric cancer in Korean patients. Korean J Intern Med. 2005; 20(2): 116-122.
23)
Ferrasi AC, Pinheiro NA, Rabenhorst SH et al. Helicobacter pylori and EBV in gastric carcinomas: methylation status and microsatellite instability. World J Gastroenterol. 2010; 16(3): 312-319.
24)
Grogg KL, Lohse CM, Pankratz VS et al. Lymphocyte-rich gastric cancer: associations with Epstein-Barr virus, microsatellite instability, histology, and survival. Mod Pathol. 2003; 16(7): 641-651.
25)
Kim H, An JY, Noh SH et al. High microsatellite instability predicts good prognosis in intestinal-type gastric cancers. J Gastroenterol Hepatol. 2011; 26(3): 585-592.
26)
Kim KM, Kwon MS, Hong SJ et al. Genetic classification of intestinal-type and diffuse-type gastric cancers based on chromosomal loss and microsatellite instability. Virchows Arch. 2003; 443(4): 491-500.
27)
Lee HJ, Jang YJ, Lee EJ et al. The significance of mismatch repair genes in gastric cancer. J Cancer Res Ther. 2013; 9(1): 80-83.
28)
Lü BJ, Lai M, Cheng L et al. Gastric medullary carcinoma, a distinct entity associated with microsatellite instability-H, prominent intraepithelial lymphocytes and improved prognosis. Histopathology. 2004; 45(5): 485-492.
29)
Mizoshita T, Tsukamoto T, Cao X et al. Microsatellite instability is linked to loss of hMLH1 expression in advanced gastric cancers: lack of a relationship with the histological type and phenotype. Gastric Cancer. 2005; 8(3): 164-172.
30)
Oki E, Kakeji Y, Zhao Y et al. Chemosensitivity and survival in gastric cancer patients with microsatellite instability. Ann Surg Oncol. 2009; 16(9): 2510-2515.
31)
Solcia E, Klersy C, Mastracci L et al. A combined histologic and molecular approach identifies three groups of gastric cancer with different prognosis. Virchows Arch. 2009; 455(3): 197-211.
32)
Sugai T, Habano W, Uesugi N et al. Three independent genetic profiles based on mucin expression in early differentiated-type gastric cancers--a new concept of genetic carcinogenesis of early differentiated-type adenocarcinomas. Mod Pathol. 2004; 17(10): 1223-1234.
33)
Wu M, Semba S, Oue N et al. BRAF/K-ras mutation, microsatellite instability, and promoter hypermethylation of hMLH1/MGMT in human gastric carcinomas. Gastric Cancer. 2004; 7(4): 246-253.
34)
Kim SY, Choi YY, An JY et al. The benefit of microsatellite instability is attenuated by chemotherapy in stage II and stage III gastric cancer: Results from a large cohort with subgroup analyses. Int J Cancer. 2015; 137(4): 819-825.
35)
Choi YY, Bae JM, An JY et al. Is microsatellite instability a prognostic marker in gastric cancer? A systematic review with meta-analysis. J Surg Oncol. 2014; 110(2): 129-135.
36)
Cristescu R, Lee J, Nebozhyn M et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015; 21(5): 449-456.
結腸・直腸がん 検査法 症例数 Stage dMMR頻度
Huang YQ et al. 2010* MSI 303 I-IV 11.9%
Hampel H et al. 2005 MSI 1066 N.R. 12.7%
Guastadisegni C et al. 2010 MSI 9243 I-IV 13.8%
Karahan B et al. 2015 IHC 186 I-III11.8% 11.8%
Gryfe R et al. 2000 IHC 607(50歳以下) I-IV 17%
Tran B et al. 2011 MSI/IHC 350 IV 11%
Koopman M et al. 2009 MSI/IHC 515 IV 3.5%
Wang L et al. 2003 MSI/IHC 293 N.R. 42%
Venderbosch S et al. 2014 IHC 3063 IV 5%
Müller CI et al. 2008 MSI 104 IV 4%
Goldstein J et al. 2014 MSI/IHC 870 I-IV 6%
Asaka S et al. 2009* MSI 940 I-IV 5.9%
Kajiwara T et al. 2016* MSI 853 IV 1.9%
1)
Huang YQ, Yuan Y, Ge WT et al. Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients. J Zhejiang Univ Sci B. 2010; 11(9): 647-653.
2)
Hampel H, Frankel WL, Martin E et al. Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med. 2005; 352(18): 1851-1860.
3)
Guastadisegni C, Colafranceschi M, Ottini et al. Microsatellite instability as a marker of prognosis and response to therapy: a meta-analysis of colorectal cancer survival data. Eur J Cancer. 2010; 46(15): 2788-2798.
4)
Karahan B, Argon A, Yıldırım M et al. Relationship between MLH-1, MSH-2, PMS-2,MSH-6 expression and clinicopathological features in colorectal cancer. Int J Clin Exp Pathol. 2015; 8(4): 4044-4053.
5)
Gryfe R, Kim H, Hsieh ET et al. Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med. 2000; 342(2): 69-77.
6)
Tran B, Kopetz S, Tie J et al. Impact of BRAF mutation and microsatellite instability on the pattern of metastatic spread and prognosis in metastatic colorectal cancer. Cancer. 2011; 117(20): 4623-4632.
7)
Koopman M, Kortman GA, Mekenkamp L et al. Deficient mismatch repair system in patients with sporadic advanced colorectal cancer. Br J Cancer. 2009; 100(2): 266-273.
8)
Wang L, Cunningham JM, Winters JL et al. BRAF mutations in colon cancer are not likely attributable to defective DNA mismatch repair. Cancer Res. 2003; 63(17): 5209-5212.
9)
Venderbosch S, Nagtegaal ID, Maughan TS et al. Mismatch repair status and BRAF mutation status in metastatic colorectal cancer patients: a pooled analysis of the CAIRO, CAIRO2, COIN, and FOCUS studies. Clin Cancer Res. 2014; 20(20): 5322-5330.
10)
Müller 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(11): 1033-1039.
11)
Goldstein J, Tran B, Ensor J et al. Multicenter retrospective analysis of metastatic colorectal cancer (CRC) with high-level microsatellite instability (MSI-H). Ann Oncol. 2014; 25(5): 1032-1038.
12)
Asaka S, Arai Y, Nishimura Y et al. Microsatellite instability-low colorectal cancer acquires a KRAS mutation during the progression from Dukes' A to Dukes' B. Carcinogenesis. 2009; 30(3): 494-499.
13)
Kajiwara T, Shitara K, Denda T et al. The Nationwide Cancer Genome Screening Project for Gastrointestinal Cancer in Japan (GI-SCREEN): MSI-status and cancer-related genome alterations in advanced colorectal cancer (CRC)—GI-SCREEN 2013-01-CRC sub-study. J Clin Oncol. 2016; 24(suppl_15): abstr 3573.
食道がん 検査法 症例数 Stage dMMR頻度
Kubo N et al.2004 MSI 42 I-IV 14.3%
Hayashi M et al. 2003 MSI 30 I-IV 3.3%
Kulke MH et al. 2001 MSI/IHC 80 I-IV 0%
1)
Kubo N, Yashiro M, Ohira M etal. Frequent microsatellite instability in primary esophageal carcinoma associated with extraesophageal primary carcinoma. Int J Cancer. 2005; 114(2): 166-173.
2)
Hayashi M, Tamura G, Jin Z et al. Microsatellite instability in esophageal squamous cell carcinoma is not associated with hMLH1 promoter hypermethylation. Pathol Int. 2003; 53(5): 270-276.
3)
Kulke MH, Thakore KS, Thomas G et al. Microsatellite instability and hMLH1/hMSH2 expression in Barrett esophagus-associated adenocarcinoma. Cancer. 2001; 91(8): 1451-1457.
卵巣がん 検査法 症例数 Stage dMMR頻度
Huang HN et al.2015* MSI/IHC 26(endometroid) N.R. 4%
    19(卵巣・子宮内膜がん合併) N.R. 21%
V S et al. 2014 MSI/IHC 88(上皮性) N.R. 68.2%
Lee JH et al. 2014 MSI 834 I-IV 14.9%
  IHC 834 I-IV 27.3%
Chui MH et al.2013 IHC 84(mucinous) N.R. 4.8%
    739(serous)   3.0%
    207(endometroid) . 11.6%
    145(clear cell) . 13.7%
  MSI 27(mucinous) N.R. 18.5%
    271(serous)   12.9%
    140(endometrioid)   18.6%
    102(clear cell)   15.7%
Caliman LP et al. 2012 MSI 13 I-IV 84.6%
Aysal A et al. 2012 IHC 71 I-IV 17%
Murphy MA et al.2011 MSI 564(Serous) I-IV 7.9%
    314(endometrioid)   19.2%
    117(clear cell)   11.5%
    101(mucinous)   16.9%
Allen HJ et al. 2000 MSI 26 I-IV 4%
Buller et al. 2001 MSI 116 I-IV 20%
Dellas A et al. 2004 MSI/IHC 77 I-III 26%
Geisler JP et al. 2003 MSI/IHC 87(Serous) N.R. 13%
    22(endometrioid) N.R. 27%
    9(mucinous) N.R. 22%
    4(clear cell) N.R. 0%
Segev Y et al. 2014 MSI 917(上皮性) N.R. 14%
1)
Huang HN, Lin MC, Tseng LH et al. Ovarian and endometrial endometrioid adenocarcinomas have distinct profiles of microsatellite instability, PTEN expression, and ARID1A expression. Histopathology. 2015; 66(4): 517-528.
2)
V S, Bhagat R, C S P et al. Microsatellite instability, promoter methylation and protein expression of the DNA mismatch repair genes in epithelial ovarian cancer. Genomics. 2014; 104(4): 257-263.
3)
Lee JH, Cragun D, Thompson Z et al. Association between IHC and MSI testing to identify mismatch repair-deficient patients with ovarian cancer. Genet Test Mol Biomarkers. 2014; 18(4): 229-235.
4)
Chui MH, Gilks CB, Cooper K et al. Identifying Lynch syndrome in patients with ovarian carcinoma: the significance of tumor subtype. Adv Anat Pathol. 2013; 20(6): 378-386.
5)
Caliman LP, Tavares RL, Piedade JB et al. Evaluation of microsatellite instability in women with epithelial ovarian cancer. Oncol Lett. 2012; 4(3): 556-560.
6)
Aysal A, Karnezis A, Medhi I et al. Ovarian endometrioid adenocarcinoma: incidence and clinical significance of the morphologic and immunohistochemical markers of mismatch repair protein defects and tumor microsatellite instability. Am J Surg Pathol. 2012; 36(2): 163-172.
7)
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(8): 1914-1922.
8)
Allen HJ, DiCioccio RA, Hohmann P et al. Microsatellite instability in ovarian and other pelvic carcinomas. Cancer Genet Cytogenet. 2000; 117(2): 163-166.
9)
Buller RE, Shahin MS, Holmes RW et al. p53 Mutations and microsatellit Yin and yang. Am J Obstet Gynecol. 2001; 184(5): 891-902.
10)
Dellas A, Puhl A, Schraml P et al. Molecular and clinicopathological analysis of ovarian carcinomas with and without microsatellite instability. Anticancer Res. 2004; 24(1): 361-369.
11)
Geisler JP, Goodheart MJ, Sood AK et al. Mismatch repair gene expression defects contribute to microsatellite instability in ovarian carcinoma. Cancer. 2003; 98(10): 2199-2206.
12)
Segev Y, Pal T, Rosen B et al. Risk factors for ovarian cancers with and without microsatellite instability. Int J Gynecol Cancer. 2014; 24(4): 664-669.
乳がん 検査法 症例数 Stage dMMR頻度
Siah SP et al. 2000 MSI 66 (<45歳) N.R. 0%
Sarrió D et al. 2003 MSI/IHC 51 N.R. 0%
Wen YH et al.2012 MSI/IHC 316 N.R. 1.3%
Lacroix-Triki M et al. 2010 MSI/IHC 315 N.R. 0%
Adem C et al. 2003 MSI 34 N.R. 0%
Demokan S et al. 2002 MSI 38 N.R. 5.3%
Murata H et al. 2002 MSI 30 N.R. 20%
1)
Siah SP, Quinn DM, Bennett GD et al. Microsatellite instability markers in breast cancer: a review and study showing MSI was not detected at 'BAT 25' and 'BAT 26' microsatellite markers in early-onset breast cancer. Breast Cancer Res Treat. 2000; 60(2): 135-142.
2)
Sarrió D, Moreno-Bueno G, Hardisson D et al. Epigenetic and genetic alterations of APC and CDH1 genes in lobular breast cancer: relationships with abnormal E-cadherin and catenin expression and microsatellite instability. Int J Cancer. 2003; 106(2): 208-215.
3)
Wen YH, Brogi E, Zeng Z et al. DNA mismatch repair deficiency in breast carcinoma: a pilot study of triple-negative and non-triple-negative tumors. Am J Surg Pathol. 2012; 36(11): 1700-1708.
4)
Lacroix-Triki M, Lambros MB, Geyer FC et al. Absence of microsatellite instability in mucinous carcinomas of the breast. Int J Clin Exp Pathol. 2010; 4(1): 22-31.
5)
Adem C, Soderberg CL, Cunningham JM et al. Microsatellite instability in hereditary and sporadic breast cancers. Int J Cancer. 2003; 107(4): 580-582.
6)
Demokan S, Muslumanoglu M, Yazici H et al. Investigation of microsatellite instability in Turkish breast cancer patients. Pathol Oncol Res. 2002; 8(2): 138-141.
7)
Murata H, Khattar NH, Kang Y et al. Genetic and epigenetic modification of mismatch repair genes hMSH2 and hMLH1 in sporadic breast cancer with microsatellite instability. Oncogene. 2002; 21(37): 5696-5703.
頭蓋内腫瘍 検査法 症例数 Stage dMMR頻度
Rodríguez-Hernández I et al. 2013 MSI/IHC 96 (星細胞腫) N.R. 43%
Viana-Pereira M et al. 2011 MSI/IHC 144 (神経膠腫) N.R. 0.7%
Pollack IF et al. 2010 MSI 68 (膠芽腫・神経膠腫・星細胞種含む) N.R. 4.4%
Viana-Pereira M et al. 2009 MSI/IHC 36 (髄芽腫) N.R. 2.8%
Maxwell JA et al. 2008 MSI/IHC 52 (神経膠腫) N.R. 0%
Vladimirova V et al. 2008 MSI/IHC 126 (星細胞腫) N.R. 0%
Eckert A et al. 2007 MSI/IHC 619 (神経膠腫) N.R. 0.16%
Martinez R et al. 2005 MSI/IHC 109 (膠芽腫) N.R. 5.5%
Alonso M et al. 2001 MSI 206 (頭蓋内腫瘍全て) N.R. 7.8%
1)
Rodríguez-Hernández I, Garcia JL, Santos-Briz A et al. Integrated analysis of mismatch repair system in malignant astrocytomas. PLoS One. 2013; 8(9): e76401.
2)
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(5): e20588.
3)
Pollack IF, Hamilton RL, Sobol RW et al. Mismatch repair deficiency is an uncommon mechanism of alkylator resistance in pediatric malignant gliomas: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010; 55(6): 1066-1071.
4)
Viana-Pereira M, Almeida I, Sousa S et al. Analysis of microsatellite instability in medulloblastoma. Neuro Oncol. 2009; 11(5): 458-467.
5)
Maxwell JA, Johnson SP, McLendon RE et al. Mismatch repair deficiency does not mediate clinical resistance to temozolomide in malignant glioma. Clin Cancer Res. 2008; 14(15): 4859-4868.
6)
Vladimirova V, Denkhaus D, Soerensen N et al. Low level of microsatellite instability in paediatric malignant astrocytomas. Neuropathol Appl Neurobiol. 2008; 34(5): 547-554.
7)
Eckert A, Kloor M, Giersch A et al. Microsatellite instability in pediatric and adult high-grade gliomas. Brain Pathol. 2007; 17(2): 146-150.
8)
Martinez R, Schackert HK, Appelt H et al. Low-level microsatellite instability phenotype in sporadic glioblastoma multiforme. J Cancer Res Clin Oncol. 2005; 131(2): 87-93.
9)
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(5): 2124-2128.
膵がん 検査法 症例数 Stage dMMR頻度
Fujii K et al. 2009* MSI 21 N.R. 0%
Yamamoto H et al. 2001* MSI 100 (4例リンチ症候群) I-IV 13% (リンチ症候群では100%)
Nakata B et al. 2002* MSI 46 I-IV 17.4%
Laghi L et al. 2012 MSI 338 I-IV 0.3%
Lüttges J et al. 2003 MSI 23 I-IV 4.3%
Wilentz RE et al. 2000 MSI 18 N.R. 22.2%
de Wilde RF et al. 2011 MSI 6 N.R. 0%
Abraham SC et al. 2002 MSI 13 N.R. 1%
1)
Fujii K, Miyashita K, Yamada Y et al. Simulation-based analyses reveal stable microsatellite sequences in human pancreatic cancer. Cancer Genet Cytogenet. 2009; 189(1): 5-14.
2)
Yamamoto H, Itoh F, Nakamura H et al. Genetic and clinical features of human pancreatic ductal adenocarcinomas with widespread microsatellite instability. Cancer Res. 2001; 61(7): 3139-3144.
3)
Nakata B, Wang YQ, Yashiro M et al. Prognostic value of microsatellite instability in resectable pancreatic cancer. Clin Cancer Res. 2002; 8(8): 2536-2540.
4)
Laghi L, Beghelli S, Spinelli A et al. Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma. PLoS One. 2012; 7(9): e46002.
5)
Lüttges J, Beyser K, Pust S et al. Pancreatic mucinous noncystic (colloid) carcinomas and intraductal papillary mucinous carcinomas are usually microsatellite stable. Mod Pathol. 2003; 16(6): 537-542.
6)
Wilentz RE, Goggins M, Redston M et al. Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: A newly described and characterized entity. Am J Pathol. 2000; 156(5): 1641-1651.
7)
de Wilde RF, Ottenhof NA, Jansen M et al. Analysis of LKB1 mutations and other molecular alterations in pancreatic acinar cell carcinoma. Mod Pathol. 2011; 24(9): 1229-1236.
8)
Abraham SC, Wu TT, Hruban RH et al. Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway. Am J Pathol. 2002; 160(3): 953-962.
胆道がん 検査法 症例数 Stage dMMR頻度
Roa JC et al. 2005 MSI/IHC 59 (胆嚢がん) I-IV 10.1%
(進行がんに限ると10%)
Yanagisawa N et al. 2003* MSI 17 (胆嚢がん) Tis-T3 5.9%
Nagai M et al. 2002* MSI 17 (胆嚢がん) I-IV 41.2%
  8 (肝外胆管がん) I-IV 87.5%
Sessa F et al. 2003 MSI 71 (胆嚢がん) N.R. 0%
Kim YT et al. 2001* MSI 15 (胆嚢がん) I-IV 20%
Yoshida T et al. 2000* MSI 30 (胆嚢がん) N.R. 17%
Suto T et al. 2001* MSI 38 (肝外胆管がん) Tis-T3 13.2%
    16 (乳頭部がん) Tis-T3 12.5%
Winkelmann R et al. 2018 MSI 102 (胆管がん) I-IV 1.0%
Rashid A et al. 2002* MSI 126 (胆道がん) I-IV 3.2%
Nagahashi M et al. 2008* MSI 34 (胆嚢がん) N.R. 26.5%
Mishra PK et al. 2011 MSI 70 (胆嚢がん) N.R. 10%
Saetta AA et al. 2006 MSI 37 (胆嚢がん) I-IV 24.3%
Kim SG et al. 2003* MSI 18 (胆管がん) I-II 5.6%
    12 (乳頭部がん) I-III 22.2%
Abraham SC et al. 2002 MSI 17 (胆管がん) N.R. 11.8%
Ruemmele P et al. 2009 IHC 144 (乳頭部がん) I-IV 10.4%
Park S et al. 2003 MSI 32 (乳頭部がん) I-IV 0%
Sessa F et al. 2007 MSI/IHC 53 (乳頭部がん) I-III 9.4%
Iacono C et al. 2007 MSI 42 (乳頭部がん) T1-4 11.9%
Moy AP et al. 2015 IHC 77 O-IV 7.8%
1)
Roa JC, Roa I, Correa P et al. Microsatellite instability in preneoplastic and neoplastic lesions of the gallbladder. J Gastroenterol. 2005; 40(1): 79-86.
2)
Yanagisawa N, Mikami T, Yamashita K et al. Microsatellite instability in chronic cholecystitis is indicative of an early stage in gallbladder carcinogenesis. Am J Clin Pathol. 2003; 120(3): 413-417.
3)
Nagai M, Watanabe M, Iwase T et al. Clinical and genetic analysis of noncancerous and cancerous biliary epithelium in patients with pancreaticobiliary maljunction. World J Surg. 2002; 26(1): 91-98.
4)
Sessa F, Furlan D, Genasetti A et al. Microsatellite instability and p53 expression in gallbladder carcinomas. Diagn Mol Pathol. 2003; 12(2): 96-102.
5)
Kim YT, Kim J, Jang YH et al. Genetic alterations in gallbladder adenoma, dysplasia and carcinoma. Cancer Lett. 2001; 169(1): 59-68.
6)
Yoshida T, Sugai T, Habano W et al. Microsatellite instability in gallbladder carcinoma: two independent genetic pathways of gallbladder carcinogenesis. J Gastroenterol. 2000; 35(10): 768-774.
7)
Suto T, Habano W, Sugai T et al. Infrequent microsatellite instability in biliary tract cancer. J Surg Oncol. 2001; 76(2): 121-126.
8)
Winkelmann R, Schneider M, Hartmann S et al. Microsatellite Instability Occurs Rarely in Patients with Cholangiocarcinoma: A Retrospective Study from a German Tertiary Care Hospital. Int J Mol Sci. 2018; 19(5): E1421.
9)
Rashid A, Ueki T, Gao YT et al. K-ras mutation, p53 overexpression, and microsatellite instability in biliary tract cancers: a population-based study in China. Clin Cancer Res. 2002; 8(10): 3156-3163.
10)
Nagahashi M, Ajioka Y, Lang I et al. Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary. World J Gastroenterol. 2008; 14(1): 70-75.
11)
Mishra PK, Raghuram GV, Jatawa SK et al. Frequency of genetic alterations observed in cell cycle regulatory proteins and microsatellite instability in gallbladder adenocarcinoma: a translational perspective. Asian Pac J Cancer Prev. 2011; 12(2): 573-574.
12)
Saetta AA, Gigelou F, Papanastasiou PI et al. High-level microsatellite instability is not involved in gallbladder carcinogenesis. Exp Mol Pathol. 2006; 80(1): 67-71.
13)
Kim SG, Chan AO, Wu TT et al. Epigenetic and genetic alterations in duodenal carcinomas are distinct from biliary and ampullary carcinomas. Gastroenterology. 2003; 124(5): 1300-1310.
14)
Abraham SC, Lee JH, Boitnott JK et al. Microsatellite instability in intraductal papillary neoplasms of the biliary tract. Mod Pathol. 2002; 15(12): 1309-1317.
15)
Ruemmele P, Dietmaier W, Terracciano L et al. Histopathologic features and microsatellite instability of cancers of the papilla of vater and their precursor lesions. Am J Surg Pathol. 2009; 33(5): 691-704.
16)
Park S, Kim SW, Kim SH et al. Lack of microsatellite instability in neoplasms of ampulla of Vater. Pathol Int. 2003; 53(10): 667-670.
17)
Sessa F, Furlan D, Zampatti C et al. Prognostic factors for ampullary adenocarcinomas: tumor stage, tumor histology, tumor location, immunohistochemistry and microsatellite instability. Virchows Arch. 2007; 451(3): 649-657.
18)
Iacono C, Verlato G, Zamboni G et al. Adenocarcinoma of the ampulla of Vater: T-stage, chromosome 17p allelic loss, and extended pancreaticoduodenectomy are relevant prognostic factors. J Gastrointest Surg. 2007; 11(5): 578-588.
19)
Moy AP, Shahid M, Ferrone CR et al. Microsatellite instability in gallbladder carcinoma. Virchows Arch. 2015; 466(4): 393-402.
小腸がん 検査法 症例数 Stage dMMR頻度
Muneyuki T et al. 2000* MSI 20 N.R. 25%
Gu MJ et al. 2012* IHC 195 N.R. 29.2%
Planck M et al. 2003 MSI/IHC 89 N.R. 13.5%
    43 (<60歳未満) N.R. 14.0%
Brueckl WM et al. 2004 MSI/IHC 35 I-IV 28.6%
Warth A et al. 2011 MSI 37 N.R. 24.3%
Overman MJ et al. 2010 MSI/IHC 54 I-IV 33.3%
(StageIVに限ると20%)
Kim SG et al. 2003* MSI 12 (十二指腸がんのみ) II-III 33.3%
Potter DD et al. 2004 MSI 11 (セリアック病)
22 (セリアック病でない)
I-IV 72.7%
9.1%
Bergmann F et al. 2010 MSI 3 (セリアック病)
20 (セリアック病でない)
N.R. 100%
20%
Schulmann K et al. 2005 MSI 21 (リンチ症候群) I-IV 95.2%
1)
Muneyuki T, Watanabe M, Yamanaka M et al. Combination analysis of genetic alterations and cell proliferation in small intestinal carcinomas. Dig Dis Sci. 2000; 45(10): 2022-2028.
2)
Gu MJ, Bae YK, Kim A et al. Expression of hMLH1, hMSH2 and hMSH6 in small intestinal carcinomas. Hepatogastroenterology. 2012; 59(119): 2228-2232.
3)
Planck M, Ericson K, Piotrowska Z et al. Microsatellite instability and expression of MLH1 and MSH2 in carcinomas of the small intestine. Cancer. 2003; 97(6): 1551-1557.
4)
Brueckl WM, Heinze E, Milsmann C et al. Prognostic significance of microsatellite instability in curatively resected adenocarcinoma of the small intestine. Cancer Lett. 2004; 203(2): 181-190.
5)
Warth A, Kloor M, Schirmacher P et al. Genetics and epigenetics of small bowel adenocarcinoma: the interactions of CIN, MSI, and CIMP. Mod Pathol. 2011; 24(4): 564-570.
6)
Overman MJ, Pozadzides J, Kopetz S et al. Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine. Br J Cancer. 2010; 102(1): 144-150.
7)
Kim SG, Chan AO, Wu TT et al. Epigenetic and genetic alterations in duodenal carcinomas are distinct from biliary and ampullary carcinomas. Gastroenterology. 2003; 124(5): 1300-1310.
8)
Potter DD, Murray JA, Donohue JH et al. The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease. Cancer Res. 2004; 64(19): 7073-7077.
9)
Bergmann F, Singh S, Michel S et al. Small bowel adenocarcinomas in celiac disease follow the CIM-MSI pathway. Oncol Rep. 2010; 24(6): 1535-1539.
10)
Schulmann K, Brasch FE, Kunstmann E et al. HNPCC-associated small bowel cancer: clinical and molecular characteristics. Gastroenterology. 2005; 128(3): 590-599.
前立腺がん 検査法 症例数 Stage dMMR頻度
Azzouzi AR et al. 2007 MSI 50 N.R. 8%
Burger M et al. 2006 MSI 79 T2-3 1%
1)
Azzouzi AR, Catto JW, Rehman I et al. Clinically localised prostate cancer is microsatellite stable. BJU Int. 2007; 99(5): 1031-1035.
2)
Burger M, Denzinger S, Hammerschmied CG et al. Elevated microsatellite alterations at selected tetranucleotides (EMAST) and mismatch repair gene expression in prostate cancer. J Mol Med (Berl). 2006; 84(10): 833-841.
尿路上皮がん 検査法 症例数 Stage dMMR頻度
Urakami S et al. 2018* IHC 143 I-II 5%
Reis H et al. 2018 MSI 70 I-IV 0%
Metcalfe MJ et al. 2018 IHC 115 I-IV 11.3%
  MSI 115 I-IV 6%
Harper HL et al. 2017 IHC 215 I-IV 7%
1)
Urakami S, Inoshita N, Oka S et al. Clinicopathological characteristics of patients with upper urinary tract urothelial cancer with loss of immunohistochemical expression of the DNA mismatch repair proteins in universal screening. Int J Urol. 2018; 25(2): 151-156.
2)
Reis H, van der Vos KE, Niedworok C et al. Pathogenic and targetable genetic alterations in 70 urachal adenocarcinomas. Int J Cancer. 2018. [Epub ahead of print]
3)
Metcalfe MJ, Petros FG, Rao P et al. Universal Point of Care Testing for Lynch Syndrome in Patients with Upper Tract Urothelial Carcinoma. J Urol. 2018; 199(1): 60-65.
4)
Harper HL, McKenney JK, Heald B et al. Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and lynch syndrome. Mod Pathol. 2017; 30(1): 146-156.
脂腺系腫瘍 検査法 症例数 Stage dMMR頻度
Jessup C J et al. 2016 IHC 15 N.R. 60%
Everett J. N et al. 2014 MSI/IHC 77 N.R. 49%
Rajan Kd A et al. 2014 IHC 10 N.R. 60%
C.A. Harwood et al. 2001 MSI 10 N.R. 40%
1)
Jessup C J, Redston M, Tilton E et al. Importance of universal mismatch repair protein immunohistochemistry in patients with sebaceous neoplasia as an initial screening tool for Muir-Torre syndrome. Hum Pathol, 2016; 49: 1-9.
2)
Everett J. N., Raymond V.M., Dandapani M et al. Screening for germline mismatch repair mutations following diagnosis of sebaceous neoplasm. JAMA Dermatol, 2014; 150: 1315-1321.
3)
Rajan Kd A, Burris C, Iliff N et al. DNA mismatch repair defects and microsatellite instability status in periocular sebaceous carcinoma. Am J Ophthalmol. 2014; 157(3): 640-647.
4)
C.A. Harwood, V.J. Swale, V.A. Bataille et al. An association between sebaceous carcinoma and microsatellite instability in immunosuppressed organ transplant recipients. J Invest Dermatol, 2001; 116 (2): 246-253.