title: Expression profiling using a cDNA array and immunohistochemistry for the extracellular matrix genes FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 in colorectal carcinoma progression and dissemination.
abstract: Colorectal cancer dissemination depends on extracellular matrix genes related to remodeling and degradation of the matrix structure. This investigation intended to evaluate the association between FN-1, ITGA-3, ITGB-5, MMP-2, and MMP-9 gene and protein expression levels in tumor tissue with clinical and histopathological neoplastic parameters of cancer dissemination. The expression associations between ECM molecules and selected epithelial markers EGFR, VEGF, Bcl2, P53, and KI-67 have also been examined in 114 patients with colorectal cancer who underwent primary tumor resection. Quantitative real-time PCR and immunohistochemistry tissue microarray methods were performed in samples from the primary tumors. The gene expression results showed that the ITGA-3 and ITGB-5 genes were overexpressed in tumors with lymph node and distant metastasis (III/IV-stage tumors compared with I/II tumors). The MMP-2 gene showed significant overexpression in mucinous type tumors, and MMP-9 was overexpressed in villous adenocarcinoma histologic type tumors. The ECM genes MMP9 and ITGA-3 have shown a significant expression correlation with EGFR epithelial marker. The overexpression of the matrix extracellular genes ITGA-3 and ITGB-5 is associated with advanced stage tumors, and the genes MMP-2 and MMP-9 are overexpressed in mucinous and villous adenocarcinoma type tumors, respectively. The epithelial marker EGFR overactivity has been shown to be associated with the ECM genes MMP-9 and ITGA-3 expression.
authors.affiliation: Postgraduate Program in Interdisciplinary Surgery Science, UNIFESP-Escola Paulista de Medicina, São Paulo, SP 04023-062, Brazil ; Research and Teaching Unit of Hospital Municipal Dr. Munir Rafful, Volta Redonda, RJ 27277-130, Brazil.
authors.forename: Suzana Angelica Silva
authors.initials: SA
authors.lastname: Lustosa
authors.affiliation: Postgraduate Program in Interdisciplinary Surgery Science, UNIFESP-Escola Paulista de Medicina, São Paulo, SP 04023-062, Brazil ; Hospital de Cancer de Barretos-Fundação Pio XII, Barretos, SP 14784-400, Brazil.
authors.forename: Luciano de Souza
authors.initials: Lde S
authors.lastname: Viana
authors.affiliation: Postgraduate Program in Interdisciplinary Surgery Science, UNIFESP-Escola Paulista de Medicina, São Paulo, SP 04023-062, Brazil ; Hospital de Cancer de Barretos-Fundação Pio XII, Barretos, SP 14784-400, Brazil.
authors.forename: Renato José
authors.initials: RJ
authors.lastname: Affonso
authors.affiliation: Postgraduate Program in Interdisciplinary Surgery Science, UNIFESP-Escola Paulista de Medicina, São Paulo, SP 04023-062, Brazil ; Hospital de Cancer de Barretos-Fundação Pio XII, Barretos, SP 14784-400, Brazil.
authors.forename: Sandra Regina Morini
authors.initials: SR
authors.lastname: Silva
authors.affiliation: Postgraduate Program in Interdisciplinary Surgery Science, UNIFESP-Escola Paulista de Medicina, São Paulo, SP 04023-062, Brazil ; Hospital de Cancer de Barretos-Fundação Pio XII, Barretos, SP 14784-400, Brazil.
authors.forename: Marcos Vinicius Araujo
authors.initials: MV
authors.lastname: Denadai
authors.affiliation: Genetics Laboratory-GRAAAC, UNIFESP-Escola Paulista de Medicina, São Paulo, SP 04023-062, Brazil.
authors.forename: Silvia Regina Caminada
authors.initials: SR
authors.lastname: de Toledo
authors.affiliation: Genetics Laboratory-GRAAAC, UNIFESP-Escola Paulista de Medicina, São Paulo, SP 04023-062, Brazil.
authors.forename: Indhira Dias
authors.initials: ID
authors.lastname: Oliveira
authors.affiliation: Postgraduate Program in Interdisciplinary Surgery Science, UNIFESP-Escola Paulista de Medicina, São Paulo, SP 04023-062, Brazil.
authors.forename: Delcio
authors.initials: D
authors.lastname: Matos
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult
chemical_list: D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins
references.citation: Lab Invest. 2001 Oct;81(10):1331-8
references.pmid: 11598146
references.citation: Ann Surg Oncol. 2012 Jan;19(1):318-25
references.pmid: 21455597
references.citation: Oncogene. 2004 Feb 19;23(7):1377-91
references.pmid: 14973550
references.citation: Oncology. 2013;84(2):81-91
references.pmid: 23128103
references.citation: Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5484-93
references.pmid: 18055796
references.citation: J Cell Physiol. 2002 Sep;192(3):259-67
references.pmid: 12124771
references.citation: Cancer Invest. 2010 Jan;28(1):38-43
references.pmid: 20001295
references.citation: Gut. 1992 Mar;33(3):342-6
references.pmid: 1568652
references.citation: Curr Opin Cell Biol. 2007 Oct;19(5):495-507
references.pmid: 17928215
references.citation: Int J Cell Biol. 2012;2012:219196
references.pmid: 22262973
references.citation: Nat Rev Cancer. 2010 Jan;10(1):9-22
references.pmid: 20029421
references.citation: Cancer Metastasis Rev. 2004 Jan-Jun;23(1-2):101-17
references.pmid: 15000152
references.citation: Int J Cancer. 2009 Dec 15;125(12):2893-902
references.pmid: 19551856
references.citation: Clin Cancer Res. 2001 Aug;7(8):2344-6
references.pmid: 11489811
references.citation: Cell Cycle. 2010 Apr 15;9(8):1647-59
references.pmid: 20404485
references.citation: Anticancer Res. 2007 Jul-Aug;27(4A):1863-7
references.pmid: 17649785
references.citation: J Mol Med (Berl). 1996 May;74(5):253-68
references.pmid: 8773262
references.citation: Nat Rev Cancer. 2009 Apr;9(4):293-302
references.pmid: 19262572
references.citation: Am J Pathol. 2004 Apr;164(4):1141-2
references.pmid: 15039202
references.citation: Oncol Rep. 2008 May;19(5):1285-91
references.pmid: 18425389
references.citation: Biochem J. 1989 Aug 1;261(3):1031-4
references.pmid: 2803233
references.citation: Nat Med. 1998 Jul;4(7):844-7
references.pmid: 9662379
references.citation: J Surg Oncol. 2010 Mar 1;101(3):259-69
references.pmid: 20039272
references.citation: Cancer Res. 2007 Jul 15;67(14):6544-8
references.pmid: 17638862
references.citation: Am J Clin Oncol. 2008 Feb;31(1):55-63
references.pmid: 18376229
references.citation: Bull Exp Biol Med. 2011 Jan;150(3):368-71
references.pmid: 21240356
references.citation: Mol Cancer Ther. 2009 Jul;8(7):1779-86
references.pmid: 19584238
references.citation: EMBO J. 2007 Jun 20;26(12):2832-42
references.pmid: 17541405
references.citation: Pathol Oncol Res. 2008 Mar;14(1):31-7
references.pmid: 18347934
references.citation: BMC Clin Pathol. 2013 May 24;13:16
references.pmid: 23705994
references.citation: Nat Rev Cancer. 2008 Aug;8(8):604-17
references.pmid: 18497750
references.citation: Lancet Oncol. 2010 Feb;11(2):136-46
references.pmid: 20022810
references.citation: Am J Surg Pathol. 2004 Nov;28(11):1460-5
references.pmid: 15489649
references.citation: Gut. 1993 Jun;34(6):829-36
references.pmid: 8314518
references.citation: J Gastrointest Cancer. 2009;40(3-4):91-7
references.pmid: 19921474
references.citation: Br J Cancer. 1999 Aug;80(12):1867-74
references.pmid: 10471033
references.citation: Endocr Relat Cancer. 2010 Jan 29;17(1):39-50
references.pmid: 19776289
references.citation: Rom J Morphol Embryol. 2011;52(1 Suppl):231-6
references.pmid: 21424059
references.citation: Semin Cancer Biol. 2002 Aug;12(4):261-6
references.pmid: 12147207
references.citation: Pigment Cell Melanoma Res. 2011 Apr;24(2):282-94
references.pmid: 21087420
references.citation: Colorectal Dis. 2011 Feb;13(2):154-60
references.pmid: 19888958
references.citation: Int J Epidemiol. 2010 Oct;39(5):1137-50
references.pmid: 21051364