Loss of CDX2/CK20 expression is associated with poorly differentiated carcinoma, the CpG island methylator phenotype, and adverse prognosis in microsatellite-unstable colorectal cancer

American Journal of Surgical Pathology

Volumn 37, Issue 10, 2013, Pages 1532-1541

  Kim, Jung Ho ^a,b   Rhee, Ye Young ^a   Bae, Jeong Mo ^a   Cho, Nam Yun ^a   Kang, Gyeong Hoon ^a  

^a Seoul National University College of Medicine   (South Korea)

^b Seoul National University Boramae Hospital   (South Korea)

Author keywords

CDX2; CK20; Colorectal cancer; Microsatellite instability; Prognosis

Indexed keywords

CDX2 PROTEIN, HUMAN; CYTOKERATIN 20; HOMEODOMAIN PROTEIN; TRANSCRIPTOME; TUMOR MARKER;

AGED; ARTICLE; BIOSYNTHESIS; CELL DIFFERENTIATION; COLORECTAL TUMOR; CPG ISLAND; DISEASE FREE SURVIVAL; DNA METHYLATION; FEMALE; GENETICS; HUMAN; IMMUNOHISTOCHEMISTRY; KAPLAN MEIER METHOD; MALE; METABOLISM; MICROSATELLITE INSTABILITY; MIDDLE AGED; PATHOLOGY; PHENOTYPE; PROGNOSIS; TISSUE MICROARRAY;

AGED; CELL DIFFERENTIATION; COLORECTAL NEOPLASMS; CPG ISLANDS; DISEASE-FREE SURVIVAL; DNA METHYLATION; FEMALE; HOMEODOMAIN PROTEINS; HUMANS; IMMUNOHISTOCHEMISTRY; KAPLAN-MEIER ESTIMATE; KERATIN-20; MALE; MICROSATELLITE INSTABILITY; MIDDLE AGED; PHENOTYPE; PROGNOSIS; TISSUE ARRAY ANALYSIS; TRANSCRIPTOME; TUMOR MARKERS, BIOLOGICAL;

EID: 84884514392     PISSN: 01475185     EISSN: 15320979     Source Type: Journal    
DOI: 10.1097/PAS.0b013e31829ab1c1     Document Type: Article

References (49)

1. Silberg DG, Swain GP, Suh ER, et al. Cdx1 and cdx2 expression during intestinal development. Gastroenterology. 2000;119:961-971.
2. Moll R, Zimbelmann R, Goldschmidt MD, et al. The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas. Differentiation. 1993;53:75-93.
3. Werling RW, Yaziji H, Bacchi CE, et al. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol. 2003;27:303-310.
4. Moskaluk CA, Zhang H, Powell SM, et al. Cdx2 protein expression in normal and malignant human tissues: an immunohistochemical survey using tissue microarrays. Mod Pathol. 2003;16:913-919.
5. De Lott LB, Morrison C, Suster S, et al. CDX2 is a useful marker of intestinal-type differentiation: a tissue microarray-based study of 629 tumors from various sites. Arch Pathol Lab Med. 2005;129:1100-1105.
6. Baba Y, Nosho K, Shima K, et al. Relationship of CDX2 loss with molecular features and prognosis in colorectal cancer. Clin Cancer Res. 2009;15:4665-4673.
7. Lugli A, Tzankov A, Zlobec I, et al. Differential diagnostic and functional role of the multi-marker phenotype CDX2/CK20/CK7 in colorectal cancer stratified by mismatch repair status. Mod Pathol. 2008;21:1403-1412.
8. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol. 2000;13:962-972.
9. Tot T. Cytokeratins 20 and 7 as biomarkers: usefulness in discriminating primary from metastatic adenocarcinoma. Eur J Cancer. 2002;38:758-763.
10. Miettinen M. Keratin 20: immunohistochemical marker for gastrointestinal, urothelial, and Merkel cell carcinomas. Mod Pathol. 1995;8:384-388.
11. Hinoi T, Tani M, Lucas PC, et al. Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. Am J Pathol. 2001;159:2239-2248.
12. McGregor DK, Wu TT, Rashid A, et al. Reduced expression of cytokeratin 20 in colorectal carcinomas with high levels of microsatellite instability. Am J Surg Pathol. 2004;28:712-718.
13. Kane MF, Loda M, Gaida GM, 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;57:808-811.
14. Cunningham JM, Christensen ER, Tester DJ, et al. Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability. Cancer Res. 1998;58:3455-3460.
15. Goldstein NS, Bhanot P, Odish E, et al. Hyperplastic-like colon polyps that preceded microsatellite-unstable adenocarcinomas. Am J Clin Pathol. 2003;119:778-796.
16. Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology. 2010;138:2073-2087, e2073.
17. Zlobec I, Bihl M, Foerster A, et al. Comprehensive analysis of CpG island methylator phenotype (CIMP)-high,-low, and-negative colorectal cancers based on protein marker expression and molecular features. J Pathol. 2011;225:336-343.
18. Samowitz WS, Holden JA, Curtin K, et al. Inverse relationship between microsatellite instability and K-ras and p53 gene alterations in colon cancer. Am J Pathol. 2001;158:1517-1524.
19. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science. 1993;260:816-819.
20. Benatti P, Gafa R, Barana D, et al. Microsatellite instability and colorectal cancer prognosis. Clin Cancer Res. 2005;11:8332-8340.
21. Guidoboni M, Gafa R, Viel A, et al. Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis. Am J Pathol. 2001;159:297-304.
22. Popat S, Hubner R, Houlston RS. Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol. 2005;23:609-618.
23. Guastadisegni C, Colafranceschi M, Ottini L, et al. Microsatellite instability as a marker of prognosis and response to therapy: a metaanalysis of colorectal cancer survival data. Eur J Cancer. 2010;46:2788-2798.
24. Boland CR. Clinical uses of microsatellite instability testing in colorectal cancer: an ongoing challenge. J Clin Oncol. 2007;25: 754-756.
25. Kim GP, Colangelo LH, Paik S, et al. Predictive value of microsatellite instability-high remains controversial. J Clin Oncol. 2007;25:4857-4858.
26. Bae JM, Kim MJ, Kim JH, et al. Differential clinicopathological features in microsatellite instability-positive colorectal cancers depending on CIMP status. Virchows Arch. 2011;459:55-63.
27. Rhee YY, Kim MJ, Bae JM, et al. Clinical outcomes of patients with microsatellite-unstable colorectal carcinomas depend on L1 methylation level. Ann Surg Oncol. 2012;19:3441-3448.
28. Dorard C, de Thonel A, Collura A, et al. Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis. Nat Med. 2011;17:1283-1289.
29. Bosman FT, World Health Organization, International Agency for Research on Cancer. WHO Classification of Tumours of the Digestive System. Lyon: International Agency for Research on Cancer; 2010.
30. Lee S, Cho NY, Choi M, et al. Clinicopathological features of CpG island methylator phenotype-positive colorectal cancer and its adverse prognosis in relation to KRAS/BRAF mutation. Pathol Int. 2008;58:104-113.
31. Kim JH, Shin SH, Kwon HJ, et al. Prognostic implications of CpG island hypermethylator phenotype in colorectal cancers. Virchows Arch. 2009;455:485-494.
32. Jass JR. Classification of colorectal cancer based on correlation of clinical, morphological and molecular features. Histopathology. 2007;50:113-130.
33. Winn B, Tavares R, Matoso A, et al. Expression of the intestinal biomarkers Guanylyl cyclase C and CDX2 in poorly differentiated colorectal carcinomas. Hum Pathol. 2010;41:123-128.
34. Winn B, Tavares R, Fanion J, et al. Differentiating the undifferentiated: immunohistochemical profile of medullary carcinoma of the colon with an emphasis on intestinal differentiation. Hum Pathol. 2009;40:398-404.
35. Pancione M, Di Blasi A, Sabatino L, et al. A novel case of rhabdoid colon carcinoma associated with a positive CpG island methylator phenotype and BRAF mutation. Hum Pathol. 2011;42: 1047-1052.
36. Remo A, Zanella C, Molinari E, et al. Rhabdoid carcinoma of the colon: a distinct entity with a very aggressive behavior: a case report associated with a polyposis coli and review of the literature. Int J Surg Pathol. 2012;20:185-190.
37. Chetty R, Bhathal PS. Caecal adenocarcinoma with rhabdoid phenotype: an immunohistochemical and ultrastructural analysis. Virchows Arch A Pathol Anat Histopathol. 1993;422:179-182.
38. Yang AH, Chen WY, Chiang H. Malignant rhabdoid tumour of colon. Histopathology. 1994;24:89-91.
39. Marcus VA, Viloria J, Owen D, et al. Malignant rhabdoid tumor of the colon. Report of a case with molecular analysis. Dis Colon Rectum. 1996;39:1322-1326.
40. Nakamura I, Nakano K, Nakayama K, et al. Malignant rhabdoid tumor of the colon: report of a case. Surg Today. 1999;29: 1083-1087.
41. Kono T, Imai Y, Imura J, et al. Cecal adenocarcinoma with prominent rhabdoid feature: report of a case with immunohistochemical, ultrastructural, and molecular analyses. Int J Surg Pathol. 2007;15:414-420.
42. Weisenberger DJ, Siegmund KD, Campan M, et al. CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nat Genet. 2006;38:787-793.
43. Samowitz WS, Albertsen H, Herrick J, et al. Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer. Gastroenterology. 2005;129:837-845.
44. Ogino S, Cantor M, Kawasaki T, et al. CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies. Gut. 2006;55:1000-1006.
45. Mallo GV, Soubeyran P, Lissitzky JC, et al. Expression of the Cdx1 and Cdx2 homeotic genes leads to reduced malignancy in colon cancer-derived cells. J Biol Chem. 1998;273:14030-14036.
46. Aoki K, Tamai Y, Horiike S, et al. Colonic polyposis caused by mTOR-mediated chromosomal instability in Apc+/Delta716 Cdx2+/- compound mutant mice. Nat Genet. 2003;35:323-330.
47. Bonhomme C, Duluc I, Martin E, et al. The Cdx2 homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development. Gut. 2003;52:1465-1471.
48. Carrato A. Adjuvant treatment of colorectal cancer. Gastrointest Cancer Res. 2008;2:S42-S46.
49. Kelley RK, Venook AP. Prognostic and predictive markers in stage II colon cancer: is there a role for gene expression profiling? Clin Colorectal Cancer. 2011;10:73-80.