APC protein immunoexpression in colorectal adenoma and adenocarcinoma

Journal of Coloproctology - Tập 33 - Trang 118-125 - 2013
Vivian Sati Oba Bourroul1,2, Guilherme Muniz Bourroul2, Giovanna Canato Toloi3, Rogério Tadeu Palma1,4, Celina Tizuko Fujiyama Oshima5, Thiago Simão Gomes6, Sílvia Saiuli Miki Ihara6, Jaques Waisberg7
1Service of Digestive System Surgery of Hospital do Servidor Público Estadual (HSPE), São Paulo, SP, Brazil
2Service of Digestive System Surgery of Hospital Estadual Mário Covas, Santo André, SP, Brazil
3Faculdade de Medicina do ABC, São Paulo, SP, Brazil
4Discipline of Service of Digestive System Surgery of Faculdade de Medicina do ABC, São Paulo, SP, Brazil
5Laboratory of Molecular Pathology of Escola Paulista de Medicina da Universidade Federal de São Paulo (EPM-UNIFESP), São Paulo, SP, Brazil
6Laboratory of Molecular Pathology, Departament of Pathology, EPM-UNIFESP, São Paulo, SP, Brazil
7General and Digestive System Surgery of Faculdade de Medicina do ABC, São Paulo, SP, Brazil

Tóm tắt

Abstract

Background activation of the Wnt pathway by mutated APC gene is considered the initial event in colorectal carcinogenesis. The identification of these mutations can improve the specific treatment of the adenocarcinoma.

Objective detect and evaluate wild-type APC protein in tissue from colorectal adenoma, adenocarcinoma and adjacent mucosa.

Methods 42 patients that underwent surgery for adenocarcinoma and 53 patients with resected adenomas were studied. Tissue samples from the adenocarcinoma were obtained from the tumor and from adjacent non-neoplastic mucosa located 10 cm from the proximal margin of the tumor. Adenoma tissue was obtained from representative areas. Blocks of tissue microarray (TMA) were submitted to immunohistochemistry with anti-APC, with readings of positivity and intensity of immunostaining and the score of immune expression of APC protein was obtained.

Results the APC protein immune expression score showed a significantly lower expression of APC protein in the adenoma when compared with the adenocarcinoma (p < 0.0001) and adjacent mucosa (p < 0.0001). The APC protein immune expression score in the colorectal mucosa and adjacent to the adenocarcinoma showed no significant difference (p = 0.24).

Conclusions the finding of decreased expression of APC protein in adenoma tissue may indicate that the mutated APC gene may contribute to the changes in the adenoma-carcinoma process of carcinogenesis sequence. The strong expression of protein APC in tissues from the carcinoma and adjacent mucosa suggests that in most patients in this series, the mutation of the APC gene did not participate in the oncogenesis mechanism.


Tài liệu tham khảo

Liberman, 2007, The APC E1317Q and I1307K polymorphisms in noncolorectal cancers, Biomed Pharmacother., 61, 566, 10.1016/j.biopha.2007.08.016 Pino, 2010, The chromosomal instability pathway in colon cancer, Gastroenterology., 138, 2059, 10.1053/j.gastro.2009.12.065 Wong, 2010, Polymorphisms in the adenomatous polyposis coli (APC) gene and advanced colorectal adenoma risk, Eur J Cancer., 46, 2457, 10.1016/j.ejca.2010.04.020 Powell, 1992, APC mutations occur early during colorectal tumorigenesis, Nature., 359, 235, 10.1038/359235a0 Miyoshi, 1992, Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene, Hum Mol Genet., 1, 229, 10.1093/hmg/1.4.229 Behrens J, Jerchow BA, Wurtele M, Grimm J, Asbrand C, Wirtz R, Kuhl M, Wedlich D, Birchmeier W. Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. Science. 1998 24):596-9. Minde, 2011, Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer?, Mol Cancer., 10, 1, 10.1186/1476-4598-10-101 Newton, 2010, Supressor of cytokine signaling-2 gene disruption promotes APCMin/+ tumorigenesis and activator protein1activation, Am J, 176, 2320 Maandag, 2010, A new conditional Apc-mutant mouse model for colorectal cancer, Carcinogenesis., 31, 946, 10.1093/carcin/bgq046 Zilberberg, 2010, Restoration of APC gene function in colorectal cancer cells by aminoglycoside and macrolide induced read through of premature termination codons, Gut., 59, 496, 10.1136/gut.2008.169805 Zhanker, 2009, Selective inhibition of proliferation in colorectal carcinoma cell lines expressing mutant APC or activated B-Raf, Int J Cancer., 125, 297, 10.1002/ijc.24289 Dhir, 2008, Epigenetic regulation of WNT signaling pathway genes in inflammatory bowel disease (IBD) associated neoplasia, J Gastrointest Surg, 12, 1745, 10.1007/s11605-008-0633-5 Dumas YR, He X. Wnt signaling: What the X@# is WTX! EMBO J. 2011;30:1415-7. Vincan, 2008, The upstream components of the Wnt signalling pathway in the dynamic EMT and MET associated with colorectal cancer progression, ClinExp Metastasis., 25, 657, 10.1007/s10585-008-9156-4 Samowitz, 2008, Genetic and epigenetic changes in colon cancer, Exp Mol Pathol., 85, 64, 10.1016/j.yexmp.2008.03.008 Foley, 2008, Targeted supression of β-catenin blocks intestinal adenoma formation in APC Min mice, J Gastrointest Surg., 12, 1452, 10.1007/s11605-008-0519-6 TMN Classification of Malignant Tumours. International Union Against Cancer(UICC)/American Joint Committee on Cancer (AJCC). 7th ed. New York, NY: Springer, 2010, pp 143-164. Hao, 2002, β-catenin expression is altered in human colon aberrant cript foci, Cancer Res., 61, 8085 Luo, 2006, Loss of the heterozygosity in human aberrant crypt foci (ACF), a putative precursor of colon cancer, Carcinogenesis., 27, 1153, 10.1093/carcin/bgi354 Wang, 2009, Increased expression of β-catenin, phosphorylated glycogen synthase kinase 3β, cyclin d1, and c-mycin laterally spreading colorectal tumors, J HistochemCytochem., 57, 363 Hashimoto, 2008, Hypermethylation status of APC inversely correlates with the presence of submucosal invasion in laterally spreading colorectal tumors, Mol Carcinogenesis., 47, 1, 10.1002/mc.20363 Lee, 2009, Aberrant methylation of APC, MGMT RASSF2A, and Wif-1 genes in plasma as a biomarker for easy detection of colorectal cancer, Clin Cancer Res., 15, 6185, 10.1158/1078-0432.CCR-09-0111 Yang, 2008, Interaction of Muc 2 and APC on Wnt signaling and in intestinal tumorigenesis: potential role of chronic inflammation, Cancer Res., 68, 7313, 10.1158/0008-5472.CAN-08-0598 Burgess, 2011, Wnt signaling and colon tumorigenesisa view from the periphery, Exp Cell Res., 317, 2748, 10.1016/j.yexcr.2011.08.010 Cleary, 2008, Missense polymorphisms in the adenomatous polyposis coli gene and colorectal cancer risk, Dis Colon Rectum., 51, 1467, 10.1007/s10350-008-9356-7 Weeraratna, 2002, Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma, Cancer Cell., 1, 279, 10.1016/S1535-6108(02)00045-4 Wang, 2009, Novel association of APC with intermediate filaments identified using a new versatile APC antibody, BMC Cell Biology., 10, 1, 10.1186/1471-2121-10-75