title: CD44v6 down-regulation is an independent prognostic factor for poor outcome of colorectal carcinoma.
abstract: We aim to investigate the variation of CD44v6 expression in the normal-adenoma-primary carcinoma-liver metastasis sequence and its prognostic impact on colorectal carcinomas. The difference in CD44v6 expression between the tumor center and invasive front was also assessed. Immunohistochemistry was performed for CD44v6 on two cohorts. The first was tissue microarrays including 402 primary CRCs sampled from the tumor center and the invasive margin. The second was whole-tissue sections, consisting of 217 adenomas, 72 primary carcinomas, and the corresponding metastatic carcinomas. In the first cohort, we found that CD44v6 down-regulation was inclined to lymph node metastasis and perineural invasion, and had an unfavorable prognosis compared with CD44v6 up-regulation. In the second cohort, CD44v6 expression was predominant in adenoma over primary carcinoma and liver metastasis in multiple steps (normal < adenoma > primary carcinoma and liver metastasis). In addition, our analysis showed that CD44v6 expression was decreased at the invasion front of the CRC compared with the center of the tumor. In conclusion, the maximal expression of CD44v6 in adenoma plays a crucial role in colorectal carcinogenesis, while loss of CD44v6 expression on the cell surface of the tumor edge enhances the progression of metastasis. CD44v6 down-regulation is an independent prognostic factor for strikingly worse disease-specific survival.
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang UniversityHangzhou 310058, Zhejiang, China; Key Laboratory of Disease Proteomics of Zhejiang Province Hangzhou 310058Zhejiang, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang UniversityHangzhou 310058, Zhejiang, China; Key Laboratory of Disease Proteomics of Zhejiang Province Hangzhou 310058Zhejiang, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao University Qingdao, China.
authors.forename: Dongliang
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Pathology, School of Medicine, Zhejiang UniversityHangzhou 310058, Zhejiang, China; Key Laboratory of Disease Proteomics of Zhejiang Province Hangzhou 310058Zhejiang, China.
authors.forename: Maode
authors.initials: M
authors.lastname: Lai
mesh_terms: D000236:Adenoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000276:immunology* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C112697:CD44v6 antigen; D018960:Hyaluronan Receptors
keywords: CD44v6; adenoma; colorectal carcinoma; immunohistochemistry; metastasis
references.citation: Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12160-4
references.pmid: 1465456
references.citation: Arch Biochem Biophys. 1994 May 1;310(2):504-7
references.pmid: 7513984
references.citation: Gastroenterology. 1996 Feb;110(2):362-8
references.pmid: 8566581
references.citation: Eur J Cancer. 1995 Nov;31A(12):2073-9
references.pmid: 8562168
references.citation: Br J Cancer. 1996 Aug;74(3):342-51
references.pmid: 8695347
references.citation: Anticancer Res. 1997 Jul-Aug;17(4A):2395-400
references.pmid: 9252653
references.citation: Scand J Gastroenterol. 1998 Jan;33(1):82-7
references.pmid: 9489913
references.citation: Scand J Gastroenterol. 1998 Mar;33(3):301-9
references.pmid: 9548625
references.citation: Hum Pathol. 1998 Jun;29(6):627-35
references.pmid: 9635685
references.citation: Eur J Cancer. 1998 Sep;34(10):1607-11
references.pmid: 9893637
references.citation: Virchows Arch. 2004 Nov;445(5):456-64
references.pmid: 15375658
references.citation: Oncol Rep. 2005 May;13(5):831-5
references.pmid: 15809746
references.citation: J Surg Oncol. 2007 Jun 15;95(8):652-62
references.pmid: 17443723
references.citation: J Pathol. 2007 Jul;212(3):260-8
references.pmid: 17516584
references.citation: Mol Cancer Res. 2007 Jun;5(6):553-67
references.pmid: 17579117
references.citation: Cancer J. 2008 Jan-Feb;14(1):54-61
references.pmid: 18303484
references.citation: Clin Exp Metastasis. 2008;25(6):621-8
references.pmid: 18600305
references.citation: Pathol Int. 2009 Apr;59(4):241-6
references.pmid: 19351367
references.citation: J Gastrointest Cancer. 2008;39(1-4):73-8
references.pmid: 19333790
references.citation: Am J Surg Pathol. 2009 Sep;33(9):1287-92
references.pmid: 19471152
references.citation: Histopathology. 2009 Nov;55(5):564-75
references.pmid: 19912362
references.citation: J Urol. 2010 Jun;183(6):2403-8
references.pmid: 20403620
references.citation: World J Gastroenterol. 2012 Sep 7;18(33):4549-56
references.pmid: 22969228
references.citation: J Gastroenterol Hepatol. 2000 Sep;15(9):1028-31
references.pmid: 11059932
references.citation: J Gastroenterol. 1999 Oct;34(5):582-8
references.pmid: 10535485
references.citation: Clin Cancer Res. 2013 Feb 15;19(4):785-97
references.pmid: 23251004
references.citation: Eur Urol. 2001 Feb;39(2):138-44
references.pmid: 11223672
references.citation: Dig Dis Sci. 2001 Aug;46(8):1623-8
references.pmid: 11508659
references.citation: J Surg Res. 2002 Mar;103(1):68-78
references.pmid: 11855920
references.citation: Z Gastroenterol. 2002 Apr;40(4):229-33
references.pmid: 11961731
references.citation: Int J Colorectal Dis. 2002 Jan;17(1):30-6
references.pmid: 12018451
references.citation: Lung Cancer. 2002 Nov;38(2):137-41
references.pmid: 12399124
references.citation: Clin Transl Oncol. 2014 Mar;16(3):285-92
references.pmid: 23860725
references.citation: Int J Clin Exp Pathol. 2015;8(1):692-701
references.pmid: 25755763
references.citation: Ann N Y Acad Sci. 2000 Jun;910:106-18; discussion 118-20
references.pmid: 10911909
references.citation: Exp Mol Pathol. 2003 Jun;74(3):262-6
references.pmid: 12782013
references.citation: World J Gastroenterol. 2003 Jul;9(7):1482-6
references.pmid: 12854146
references.citation: Oncol Rep. 2004 Jan;11(1):41-5
references.pmid: 14654900
references.citation: J Pathol. 2004 Jun;203(2):638-44
references.pmid: 15141378
references.citation: J Cancer Res Clin Oncol. 2004 Nov;130(11):679-86
references.pmid: 15300427
references.citation: Cancer. 1989 Feb 1;63(3):539-43
references.pmid: 2912530
references.citation: Biochim Biophys Acta. 1989 Jul 28;989(1):65-84
references.pmid: 2665818
references.citation: Cancer Res. 1993 Apr 1;53(7):1516-21
references.pmid: 8453616
references.citation: J Biol Chem. 1993 Jun 15;268(17):12235-8
references.pmid: 8509359
references.citation: Ciba Found Symp. 1995;189:142-51; discussion 151-6, 174-6
references.pmid: 7587629