Deficiency of Adenomatous Polyposis Coli protein in sporadic colorectal adenomas and its associations with clinical phenotype and histology
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
16804979
PubMed Central
PMC4087942
DOI
10.3748/wjg.v12.i24.3901
Knihovny.cz E-zdroje
- MeSH
- adenom chemie genetika patologie MeSH
- dospělí MeSH
- fenotyp MeSH
- imunohistochemie MeSH
- kolorektální nádory chemie genetika patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace MeSH
- mutační analýza DNA MeSH
- nádorové biomarkery analýza MeSH
- protein familiární adenomatózní polypózy analýza genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- nádorové biomarkery MeSH
- protein familiární adenomatózní polypózy MeSH
AIM: To evaluate the frequency of the loss of the Adenomatous Polyposis Coli (APC) protein and to compare the APC status with the characteristics of colorectal adenomas. METHODS: Immunohistochemical analysis of the APC protein was performed on 118 adenomas and the results were compared with parameters of malignant potential, location of adenomas, macroscopic appearance and age of the patients. RESULTS: A complete loss of the APC protein was found in 28 (24%) adenomas, while 90 (76%) were APC positive. The mean size of adenomas was 13.5 +/- 14.2 mm (95% CI 10.5-16.5) in APC-positive, and 13.8 +/- 15.5 mm (95% CI 7.8-19.8) in APC-negative adenomas (P = 0.364). Statistical analysis revealed no difference between APC-positive and negative adenomas as to the histological type (P = 0.327) and grade of dysplasia (P = 0.494). We found that even advanced adenomas did not differ in their APC status from the non-advanced tumors (P = 0.414). Finally, no difference was found when the location (P = 0.157), macroscopic appearance (P = 0.571) and age of patients (P = 0.438) were analysed and compared between both APC positive and negative adenomas. CONCLUSION: Most adenomas expressed full-length APC protein, suggesting that protein expression is not a reliable marker for assessment of APC gene mutation. Complete loss of APC protein did not influence morphology, location, or appearance of adenomas, nor was it affected by the patient's age.
Zobrazit více v PubMed
Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;61:759–767. PubMed
Nagase H, Nakamura Y. Mutations of the APC (adenomatous polyposis coli) gene. Hum Mutat. 1993;2:425–434. PubMed
Narayan S, Roy D. Role of APC and DNA mismatch repair genes in the development of colorectal cancers. Mol Cancer. 2003;2:41. PubMed PMC
Smith KJ, Johnson KA, Bryan TM, Hill DE, Markowitz S, Willson JK, Paraskeva C, Petersen GM, Hamilton SR, Vogelstein B. The APC gene product in normal and tumor cells. Proc Natl Acad Sci U S A. 1993;90:2846–2850. PubMed PMC
Powell SM, Zilz N, Beazer-Barclay Y, Bryan TM, Hamilton SR, Thibodeau SN, Vogelstein B, Kinzler KW. APC mutations occur early during colorectal tumorigenesis. Nature. 1992;359:235–237. PubMed
Fearnhead NS, Britton MP, Bodmer WF. The ABC of APC. Hum Mol Genet. 2001;10:721–733. PubMed
Midgley CA, White S, Howitt R, Save V, Dunlop MG, Hall PA, Lane DP, Wyllie AH, Bubb VJ. APC expression in normal human tissues. J Pathol. 1997;181:426–433. PubMed
Losi L, Di Gregorio C, Pedroni M, Ponti G, Roncucci L, Scarselli A, Genuardi M, Baglioni S, Marino M, Rossi G, et al. Molecular genetic alterations and clinical features in early-onset colorectal carcinomas and their role for the recognition of hereditary cancer syndromes. Am J Gastroenterol. 2005;100:2280–2287. PubMed
Iwamoto M, Ahnen DJ, Franklin WA, Maltzman TH. Expression of beta-catenin and full-length APC protein in normal and neoplastic colonic tissues. Carcinogenesis. 2000;21:1935–1940. PubMed
Kim JC, Koo KH, Roh SA, Cho YK, Kim HC, Yu CS, Kim HJ, Kim JS, Cho MK. Genetic and epigenetic changes in the APC gene in sporadic colorectal carcinoma with synchronous adenoma. Int J Colorectal Dis. 2003;18:203–209. PubMed
Miyaki M, Konishi M, Kikuchi-Yanoshita R, Enomoto M, Igari T, Tanaka K, Muraoka M, Takahashi H, Amada Y, Fukayama M. Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumors. Cancer Res. 1994;54:3011–3020. PubMed
Mulkens J, Poncin J, Arends JW, De Goeij AF. APC mutations in human colorectal adenomas: analysis of the mutation cluster region with temperature gradient gel electrophoresis and clinicopathological features. J Pathol. 1998;185:360–365. PubMed
Iwamoto M, Hoffenberg EJ, Carethers JM, Doctolero R, Tajima A, Sugano K, Franklin WA, Ahnen DJ. Nuclear accumulation of beta-catenin occurs commonly in the epithelial cells of juvenile polyps. Pediatr Res. 2005;57:4–9; discussion 1-3. PubMed
Lamlum H, Ilyas M, Rowan A, Clark S, Johnson V, Bell J, Frayling I, Efstathiou J, Pack K, Payne S, et al. The type of somatic mutation at APC in familial adenomatous polyposis is determined by the site of the germline mutation: a new facet to Knudson's 'two-hit' hypothesis. Nat Med. 1999;5:1071–1075. PubMed
Takayama T, Ohi M, Hayashi T, Miyanishi K, Nobuoka A, Nakajima T, Satoh T, Takimoto R, Kato J, Sakamaki S, et al. Analysis of K-ras, APC, and beta-catenin in aberrant crypt foci in sporadic adenoma, cancer, and familial adenomatous polyposis. Gastroenterology. 2001;121:599–611. PubMed
De Benedetti L, Sciallero S, Gismondi V, James R, Bafico A, Biticchi R, Masetti E, Bonelli L, Heouaine A, Picasso M. Association of APC gene mutations and histological characteristics of colorectal adenomas. Cancer Res. 1994;54:3553–3556. PubMed
Chen J, Röcken C, Lofton-Day C, Schulz HU, Müller O, Kutzner N, Malfertheiner P, Ebert MP. Molecular analysis of APC promoter methylation and protein expression in colorectal cancer metastasis. Carcinogenesis. 2005;26:37–43. PubMed
Esteller M, Sparks A, Toyota M, Sanchez-Cespedes M, Capella G, Peinado MA, Gonzalez S, Tarafa G, Sidransky D, Meltzer SJ, et al. Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. Cancer Res. 2000;60:4366–4371. PubMed
Pretlow TP, Edelmann W, Kucherlapati R, Pretlow TG, Augenlicht LH. Spontaneous aberrant crypt foci in Apc1638N mice with a mutant Apc allele. Am J Pathol. 2003;163:1757–1763. PubMed PMC
Bodmer W, Bishop T, Karran P. Genetic steps in colorectal cancer. Nat Genet. 1994;6:217–219. PubMed
Tighe A, Johnson VL, Taylor SS. Truncating APC mutations have dominant effects on proliferation, spindle checkpoint control, survival and chromosome stability. J Cell Sci. 2004;117:6339–6353. PubMed
Smith G, Carey FA, Beattie J, Wilkie MJ, Lightfoot TJ, Coxhead J, Garner RC, Steele RJ, Wolf CR. Mutations in APC, Kirsten-ras, and p53--alternative genetic pathways to colorectal cancer. Proc Natl Acad Sci U S A. 2002;99:9433–9438. PubMed PMC