title: Multicentric and multifocal versus unifocal breast cancer: differences in the expression of E-cadherin suggest differences in tumor biology.
abstract: BACKGROUND
  The aim of this study was to evaluate the expression of the cell adhesion-related glycoproteins MUC-1, β-catenin and E-cadherin in multicentric/multifocal breast cancer in comparison to unifocal disease in order to identify potential differences in the biology of these tumor types.
  
  
  METHODS
  A retrospective analysis was performed on the expression of MUC1, β-catenin and E-cadherin by immunohistochemistry on tumor tissues of a series of 112 breast cancer patients (total collective) treated in Munich between 2000 and 2002. By matched-pair analysis, 46 patients were entered into two comparable groups of 23 patients after categorizing them as having multicentric/multifocal or unifocal breast cancer. Matching criteria were tumor size, histology grade and lymph node status; based on these criteria, patients were distributed equally between the two groups (p = 1.000 each). Data were analyzed with the Kruskal-Wallis and the Mann-Whitney tests.
  
  
  RESULTS
  In the matched groups, we found a significantly down-regulated expression of E-cadherin in multicentric/multifocal breast cancer compared to unifocal disease (p = 0.024). The total collective showed even higher significance with a value of p < 0.0001. In contrast, no significant differences were observed in the expression of β-catenin between multicentric/multifocal and unifocal tumors (p = 0.636 and p = 0.914, respectively). When comparing the expression of MUC1, E-cadherin and β-catenin within the unifocal group, we found a significant positive correlation between E-cadherin and β-catenin (p = 0.003). In the multicentric/multifocal group we observed, in contrast to the unifocal group, a significant decrease of MUC1 expression with increased grading (p = 0.027).
  
  
  CONCLUSIONS
  This study demonstrates that multicentric/multifocal and unifocal breast cancers with identical TNM-staging clearly differ in the expression level of E-cadherin. We suggest that the down-regulation of E-cadherin in multicentric/multifocal breast cancer is causally connected with the worse prognosis of this tumor type.
authors.affiliation: Frauenklinik, Klinikum der Ludwig-Maximilians-Universität, Innenstadt, München, Germany. tobias.weissenbacher@med.uni-muenchen.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Weissenbacher
authors.forename: Eva
authors.initials: E
authors.lastname: Hirte
authors.forename: Christina
authors.initials: C
authors.lastname: Kuhn
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Janni
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.forename: Uwe
authors.initials: U
authors.lastname: Karsten
authors.forename: Brigitte
authors.initials: B
authors.lastname: Rack
authors.forename: Klaus
authors.initials: K
authors.lastname: Friese
authors.forename: Udo
authors.initials: U
authors.lastname: Jeschke
authors.forename: Sabine
authors.initials: S
authors.lastname: Heublein
authors.forename: Darius
authors.initials: D
authors.lastname: Dian
authors.forename: Nina
authors.initials: N
authors.lastname: Ditsch
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins
references.citation: Front Biosci. 2007 May 01;12:4020-33
references.pmid: 17485355
references.citation: BMC Cancer. 2009 Sep 14;9:325
references.pmid: 19751508
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):301-9
references.pmid: 20056651
references.citation: Tumour Biol. 2005 Jul-Aug;26(4):217-20
references.pmid: 16006776
references.citation: Histol Histopathol. 2005 Jul;20(3):791-9
references.pmid: 15944928
references.citation: Biochem Biophys Res Commun. 2009 Jun 19;384(1):6-11
references.pmid: 19379710
references.citation: Patholog Res Int. 2010 Nov 03;2011:480960
references.pmid: 21151538
references.citation: Anticancer Res. 1997 Mar-Apr;17(2B):1383-90
references.pmid: 9137503
references.citation: Tumour Biol. 1998;19 Suppl 1:1-20
references.pmid: 9422084
references.citation: Virchows Arch. 2006 Apr;448(4):500-5
references.pmid: 16538444
references.citation: Lancet Oncol. 2003 Jan;4(1):56-60
references.pmid: 12517540
references.citation: Cell Adhes Commun. 1998;6(2-3):171-84
references.pmid: 9823469
references.citation: Ann Oncol. 2008 Feb;19(2):276-83
references.pmid: 17962200
references.citation: Nat Rev Cancer. 2009 Dec;9(12):874-85
references.pmid: 19935676
references.citation: Cancer. 2013 Mar 15;119(6):1132-9
references.pmid: 23279980
references.citation: Cancer. 1988 Jun 1;61(11):2310-4
references.pmid: 3284634
references.citation: Vet J. 2009 Dec;182(3):491-3
references.pmid: 18948041
references.citation: Ann Surg Oncol. 2011 Jun;18(6):1671-7
references.pmid: 21161724
references.citation: Pathol Res Pract. 2007;203(7):517-23
references.pmid: 17576040
references.citation: Acta Gastroenterol Belg. 1999 Oct-Dec;62(4):393-402
references.pmid: 10692769
references.citation: Rev Esp Oncol. 1980;27(2):265-73
references.pmid: 7255847
references.citation: Clin Breast Cancer. 2011 Aug;11(4):258-63
references.pmid: 21729662
references.citation: PLoS One. 2010 Aug 16;5(8):e12180
references.pmid: 20808935
references.citation: Clin Cancer Res. 2010 Jun 15;16(12):3153-62
references.pmid: 20530697
references.citation: Am J Pathol. 2009 Aug;175(2):580-91
references.pmid: 19590041
references.citation: Cancer. 2005 Aug 15;104(4):700-7
references.pmid: 16003773
references.citation: Cancer Immunol Immunother. 2006 Nov;55(11):1337-47
references.pmid: 16485130
references.citation: Biochem Biophys Res Commun. 2007 Oct 26;362(3):740-6
references.pmid: 17764657
references.citation: Breast Cancer Res Treat. 2010 Jul;122(1):27-34
references.pmid: 20454925
references.citation: Cancer Treat Rev. 2001 Jun;27(3):137-42
references.pmid: 11417963
references.citation: Pathology. 2006 Oct;38(5):403-7
references.pmid: 17008277
references.citation: Ann Surg Oncol. 2007 Jan;14(1):143-7
references.pmid: 17058125
references.citation: Histopathology. 1991 Nov;19(5):403-10
references.pmid: 1757079
references.citation: Ann Surg Oncol. 2000 Sep;7(8):581-7
references.pmid: 11005556
references.citation: Oncogene. 2010 Feb 11;29(6):920-9
references.pmid: 19915608
references.citation: Histopathology. 2007 Sep;51(3):322-35
references.pmid: 17645748
references.citation: Cancer Metastasis Rev. 2009 Jun;28(1-2):151-66
references.pmid: 19153669
references.citation: Breast. 2006 Feb;15(1):3-8
references.pmid: 16473737
references.citation: Nan Fang Yi Ke Da Xue Xue Bao. 2009 Nov;29(11):2237-40
references.pmid: 19923077
references.citation: Onkologie. 2009 May;32(5):238-44
references.pmid: 19420969
references.citation: Histopathology. 2007 Aug;51(2):227-38
references.pmid: 17650217
references.citation: Eur J Cancer. 2010 Jul;46(11):1990-6
references.pmid: 20385484