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APC and β-catenin protein expression patterns in HNPCC-related endometrial and colorectal cancers

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Abstract

Objective: The adenomatous polyposis coli (APC) and β-catenin (CTNNB1) genes are the two major components of the Wnt signaling pathway that has been shown to play an important role in the formation of certain cancers. The overactivation of the pathway, which results in abnormal accumulation of β-catenin protein in nuclei, contributes to most colorectal cancers (CRCs), both sporadic and hereditary, as well as sporadic endometrial cancers (ECs). Here, we studied the involvement of APC and β-catenin in hereditary nonpolyposis colorectal cancer (HNPCC)-related ECs, and compared the expression patterns to those in HNPCC-related CRCs. Materials and methods: Nineteen ECs and 31 CRCs derived from HNPCC patients were immunohistochemically stained with anti-APC- and anti-β-catenin –antibodies. Results: Tumor-specific loss of APC was observed in 16 of endometrial cancers (3 of 19) and in 39 of colorectal cancers (12 of 31). Consistently, the loss of APC expression was associated with nuclear β-catenin staining. Altogether, aberrant β-catenin localization was observed in 53 of ECs (10 of 19) as compared to 84 of CRCs (26 of 31) (P=0.02).Conclusion: Our results suggest a frequent overactivation of the Wnt signaling pathway in hereditary endometrial cancer. In accordance with studies on sporadic cancers, abnormal accumulation of β-catenin protein in nuclei occurred much less frequently in HNPCC-related ECs than CRCs, which may reflect organ-specific differences in their pathogenesis.

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Abbreviations

APC:

adenomatous polyposis coli

EC:

endometrial cancer

CRC:

colorectal cancer

GSK-3β:

glycogen synthase kinase −3β

HNPCC:

hereditary nonpolyposis colorectal cancer

MSI:

microsatellite instability

References

  1. B Rubinfeld I Albert E Porfiri et al. (1996) ArticleTitleBinding of GSK3β to the APC-β-catenin complex and regulation of complex assembly Science 272 1023–6 Occurrence Handle1:CAS:528:DyaK28XjtVejsrs%3D Occurrence Handle8638126

    CAS  PubMed  Google Scholar 

  2. H Aberle A Bauer J Stappert et al. (1997) ArticleTitleβ-Catenin is a target for the ubiquitin-proteosome pathway EMBO J 16 3797–804 Occurrence Handle10.1093/emboj/16.13.3797 Occurrence Handle1:CAS:528:DyaK2sXkslShsbk%3D Occurrence Handle9233789

    Article  CAS  PubMed  Google Scholar 

  3. S Kishida H Yamamoto S Ikeda et al. (1998) ArticleTitleAxin, a negative regulator of the Wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates and the stabilization of β-catenin J Biol Chem 273 10823–6 Occurrence Handle10.1074/jbc.273.18.10823 Occurrence Handle1:CAS:528:DyaK1cXjtFGktr4%3D Occurrence Handle9556553

    Article  CAS  PubMed  Google Scholar 

  4. PJ Morin AB Sparks V Korinek et al. (1997) ArticleTitleActivation of β-catenin-Tcf-signaling in colon cancer by mutations in β-catenin or APC Science 275 1787–90 Occurrence Handle10.1126/science.275.5307.1787 Occurrence Handle1:CAS:528:DyaK2sXitVGrtL0%3D Occurrence Handle9065402

    Article  CAS  PubMed  Google Scholar 

  5. M Miyaki T Iijima J Kimura et al. (1999) ArticleTitleFrequent mutation of β-catenin and APC genes in primary colorectal tumors from patients with hereditary nonpolyposis colorectal cancer Cancer Res 59 4506–9 Occurrence Handle1:CAS:528:DyaK1MXmtVKksL0%3D Occurrence Handle10493496

    CAS  PubMed  Google Scholar 

  6. M Iwamoto DJ Ahnen WA Franklin et al. (2000) ArticleTitleExpression of β-catenin and full-length APC protein in normal and neoplastic colonic tissues Carcinogenesis 1 1935–40 Occurrence Handle10.1093/carcin/21.11.1935

    Article  Google Scholar 

  7. X Hao IM Frayling TC Willcocks et al. (2002) ArticleTitleβ-Catenin expression and allelic loss at APC in sporadic colorectal carcinogenesis Virchows Arch 440 362–6 Occurrence Handle10.1007/s00428-001-0570-0 Occurrence Handle1:CAS:528:DC%2BD38Xks1GmsLg%3D Occurrence Handle11956815

    Article  CAS  PubMed  Google Scholar 

  8. AB Sparks PJ Morin B Vogelstein et al. (1998) ArticleTitleMutational analysis of the APC/β-Catenin/Tcf pathway in colorectal cancer Cancer Res 58 1130–4 Occurrence Handle1:CAS:528:DyaK1cXhvV2rsr8%3D Occurrence Handle9515795

    CAS  PubMed  Google Scholar 

  9. PW Schlosshauer EC Pirog RL Levine et al. (2000) ArticleTitleMutation analysis of the CTNBB1 and APC genes in uterine endometrioid carcinoma Mod Pathol 13 1066–71 Occurrence Handle10.1038/modpathol.3880196 Occurrence Handle1:STN:280:DC%2BD3crgtFeltQ%3D%3D Occurrence Handle11048799

    Article  CAS  PubMed  Google Scholar 

  10. J Palacios C. Gamallo (1998) ArticleTitleMutations in the β-catenin gene (CTNBB1) in endometrioid ovarian carcinomas Cancer Res 58 1344–7 Occurrence Handle1:CAS:528:DyaK1cXit1elu7w%3D Occurrence Handle9537226

    CAS  PubMed  Google Scholar 

  11. T Fukuchi M Sakamoto H Tsuda et al. (1998) ArticleTitleβ-Catenin mutation in carcinoma of the uterine endometrium Cancer Res 58 3526–8 Occurrence Handle1:CAS:528:DyaK1cXlsFajsbk%3D Occurrence Handle9721853

    CAS  PubMed  Google Scholar 

  12. K Kobayashi S Sagae Y Nishioka et al. (1999) ArticleTitleMutations of the β-catenin gene in endometrial carcinomas Jpn J Cancer Res 90 55–9 Occurrence Handle1:CAS:528:DyaK1MXhtFGqur8%3D Occurrence Handle10076565

    CAS  PubMed  Google Scholar 

  13. J Palacios L Catasus G Moreno et al. (2001) ArticleTitleβ- And γ-catenin expression in endometrial carcinoma Relationship with clinicopathological features and microsatellite instability. Virchows Arch 438 464–9 Occurrence Handle10.1007/s004280000371 Occurrence Handle1:STN:280:DC%2BD3MzksVKrtw%3D%3D Occurrence Handle11407474

    Article  CAS  PubMed  Google Scholar 

  14. PW Schlosshauer L Hedrick Ellenson RA. Soslow (2002) ArticleTitleβ-Catenin and E-cadherin expression patterns in high-grade endometrial carcinoma are associated with histological subtype Mod Pathol 15 1032–7 Occurrence Handle10.1097/01.MP.0000028573.34289.04 Occurrence Handle12379748

    Article  PubMed  Google Scholar 

  15. Y Zhai R Wu DR Schwartz et al. (2002) ArticleTitleRole of β-catenin/T-cell factor-regulated genes in ovarian endometrioid adenocarcinomas Am J Pathol 160 1229–38 Occurrence Handle1:CAS:528:DC%2BD38XjsFGjsbk%3D Occurrence Handle11943708

    CAS  PubMed  Google Scholar 

  16. Pijnenborg JMA, Kisters N, Van Engeland M et al. APC, β-catenin, and E-cadherin and the development of recurrent endometrial carcinoma. Int J Gynecol Cancer 14: 947-56

  17. M Nyström-Lahti Y Wu A-L Moisio et al. (1996) ArticleTitleDNA mismatch repair gene mutations in 55 verified or putative kindreds with hereditary nonpolyposis colorectal cancer Hum Mol Genet 5 763–9 Occurrence Handle10.1093/hmg/5.6.763 Occurrence Handle8776590

    Article  PubMed  Google Scholar 

  18. M Holmberg P Kristo RB Chadwick et al. (1998) ArticleTitleMutation sharing, predominant involvement of MLH1 gene, and description of four novel mutations in hereditary nonpolyposis colorectal cancer Hum Mutat 11 482 Occurrence Handle10.1002/(SICI)1098-1004(1998)11:6<482::AID-HUMU16>3.0.CO;2-B Occurrence Handle1:STN:280:DyaK1M3htFaiug%3D%3D

    Article  CAS  Google Scholar 

  19. P Schweizer A-L Moisio SA Kuismanen et al. (2001) ArticleTitleLack of MSH2 and MSH6 characterizes endometrial but not colon carcinomas in hereditary nonpolyposis colorectal cancer Cancer Res 61 2813–5 Occurrence Handle1:CAS:528:DC%2BD3MXivFGrur0%3D Occurrence Handle11306449

    CAS  PubMed  Google Scholar 

  20. M Aarnio R Sankila E Pukkala et al. (1999) ArticleTitleCancer risk in mutation carriers of DNA-mismatch-repair genes Int J Cancer 81 214–8

    Google Scholar 

  21. SA Kuismanen A-L Moisio P Schweizer et al. (2002) ArticleTitleEndometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability Am J Pathol 160 1953–8 Occurrence Handle1:CAS:528:DC%2BD38XltFOrsr8%3D Occurrence Handle12057899

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biological and Environmental Sciences, Genetics, University of Helsinki, Viikinkaari 5, 00014, Helsinki, Finland

    Reetta Kariola & Minna Nyström

  2. Department of Medical Genetics, University of Helsinki, Helsinki, Finland

    Wael M. Abdel-Rahman, Miina Ollikainen & Päivi Peltomäki

  3. Department of Pathology, Faculty of Medicine, Zagazig University, Egypt

    Wael M. Abdel-Rahman

  4. Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Helsinki, Finland

    Ralf Butzow

Authors
  1. Reetta Kariola
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  2. Wael M. Abdel-Rahman
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  3. Miina Ollikainen
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  4. Ralf Butzow
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  5. Päivi Peltomäki
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  6. Minna Nyström
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Correspondence to Minna Nyström.

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Kariola, R., Abdel-Rahman, W.M., Ollikainen, M. et al. APC and β-catenin protein expression patterns in HNPCC-related endometrial and colorectal cancers. Familial Cancer 4, 187–190 (2005). https://doi.org/10.1007/s10689-004-6130-4

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  • DOI: https://doi.org/10.1007/s10689-004-6130-4

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