Skip to main content

Advertisement

Log in

Immunohistochemical Expression of p16, p53, and p63 in Colorectal Adenomas and Adenocarcinomas

  • Published:
Diseases of the Colon & Rectum

Purpose

The aim of this study was to investigate the immunohistochemical expression of p16, p53, and p63 proteins according to some pathologic parameters related to colorectal adenomas and adenocarcinomas such as grade of dysplasia and histologic type.

Methods

Immunohistochemistry with the antibodies p16, p53, and p63 was performed in tubular, tubular-villous, and villous adenomas (n = 30) and in well, moderately, and poorly differentiated adenocarcinomas (n = 30). The p63-positive cases were submitted to double immunolabeling with the cytokeratin 5 (CK5).

Results

The p16 and p53 labelings were observed in some adenomas and adenocarcinomas but without any association with p63 expression, histologic type, or grade of differentiation of the neoplasm. P63 expression was found mainly in the villous adenomas and in the poorly differentiated adenocarcinomas. The poorly differentiated adenocarcinomas also exhibited coexpression of CK5 and p63.

Conclusions

Despite both p16 and p53 having been detected in colorectal neoplasms, they were not related to the different histologic variables nor to the expression of p63. However, p63 expression was closely associated with villous adenomas and poorly differentiated adenocarcinomas. Thus, p63 may represent a marker of poor differentiation in colorectal neoplasms. The coexpression of p63 and CK5 observed in this study could be related to divergent differentiation during the development of colorectal cancer, although further studies are warranted to refine the understanding of this process.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Figure 1

Similar content being viewed by others

References

  1. DM Parkin F Bray J Ferlay P Pisani (2005) ArticleTitleGlobal cancer statistics, 2002 CA Cancer J Clin 55 74–108 Occurrence Handle15761078 Occurrence Handle10.3322/canjclin.55.2.74

    Article  PubMed  Google Scholar 

  2. S Srivastava M Verma DE Henson (2001) ArticleTitleBiomarkers for early detection of colon cancer Clin Cancer Res 7 1118–1126 Occurrence Handle1:CAS:528:DC%2BD3MXktlemurg%3D Occurrence Handle11350874

    CAS  PubMed  Google Scholar 

  3. A Rashid L Shen JS Morris JP Issa SR Hamilton (2001) ArticleTitleCpG island methylation in colorectal adenomas Am J Pathol 159 1129–1135 Occurrence Handle1:CAS:528:DC%2BD3MXnt12mt74%3D Occurrence Handle11549606

    CAS  PubMed  Google Scholar 

  4. JH Bond (2000) ArticleTitlePolyp guideline: diagnosis, treatment and surveillance for patients with colorectal polyps Am J Gastroenterol 95 3053–3063 Occurrence Handle10.1111/j.1572-0241.2000.03434.x Occurrence Handle1:STN:280:DC%2BD3M%2FnsFGqsA%3D%3D Occurrence Handle11095318

    Article  CAS  PubMed  Google Scholar 

  5. MJ O'Brien SJ Winawer AG Zauber et al. (1990) ArticleTitleThe national polyp study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas Gastroenterology 98 371–379 Occurrence Handle2403953

    PubMed  Google Scholar 

  6. J Gayet XP Zhou A Duval S Rolland JM Hoang P Cottu R Hamelin (2001) ArticleTitleExtensive characterization of genetic alterations in a series of human colorectal cancer cell lines Oncogene 36 5025–5032 Occurrence Handle10.1038/sj.onc.1204611 Occurrence Handle1:CAS:528:DC%2BD3MXmtlCks70%3D

    Article  CAS  Google Scholar 

  7. A Okamoto DJ Demetrick EA Spillare et al. (1994) ArticleTitleMutations and altered expression of p16INK4 in human cancer Proc Natl Acad Sci USA 23 11045–11049

    Google Scholar 

  8. N Burri P Shaw H Bouzourene et al. (2001) ArticleTitleMethylation silencing and mutations of the p14ARF and p16INK4a genes in colon cancer Lab Invest 2 217–229

    Google Scholar 

  9. K Harms S Nozell X Chen (2004) ArticleTitleThe common and distinct target genes of the p53 family transcription factors Cell Mol Life Sci 61 822–842 Occurrence Handle10.1007/s00018-003-3304-4 Occurrence Handle1:CAS:528:DC%2BD2cXls1Grt7s%3D Occurrence Handle15095006

    Article  CAS  PubMed  Google Scholar 

  10. UM Moll N Slade (2004) ArticleTitleP63 and p73: roles in development and tumor formation Mol Cancer Res 2 371–386 Occurrence Handle1:CAS:528:DC%2BD2cXlvF2ksLY%3D Occurrence Handle15280445

    CAS  PubMed  Google Scholar 

  11. G Blandino M Dobbelstein (2004) ArticleTitleP73 and p63: why do we still need them? Cell Cycle 3 886–894 Occurrence Handle1:CAS:528:DC%2BD2MXmtlKqsQ%3D%3D Occurrence Handle15254416

    CAS  PubMed  Google Scholar 

  12. AJ Levine AJ Levine J Momand CA Finlay (1991) ArticleTitleThe p53 tumour suppressor gene Nature 351 453–456 Occurrence Handle10.1038/351453a0 Occurrence Handle1:CAS:528:DyaK3MXksVaku7g%3D Occurrence Handle2046748

    Article  CAS  PubMed  Google Scholar 

  13. CJ Como ParticleDi MJ Urist I Babayan et al. (2002) ArticleTitleP63 expression profiles in human normal and tumor tissues Clin Cancer Res 2 494–501

    Google Scholar 

  14. JS Reis-Filho PT Simpson A Martins A Preto F Gartner FC Schmitt (2003) ArticleTitleDistribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray Virchows Arch 2 122–132

    Google Scholar 

  15. K Nylander B Vojtesek R Nenutil et al. (2002) ArticleTitleDifferential expression of p63 isoforms in normal tissues and neoplastic cells J Pathol 4 417–427 Occurrence Handle10.1002/path.1231 Occurrence Handle1:CAS:528:DC%2BD3sXnt12rsQ%3D%3D

    Article  CAS  Google Scholar 

  16. L Muzio ParticleLo A Santarelli R Caltabiano et al. (2005) ArticleTitleP63 overexpression associates with poor prognosis in head and neck squamous cell carcinoma Hum Pathol 2 187–194 Occurrence Handle10.1016/j.humpath.2004.12.003 Occurrence Handle1:CAS:528:DC%2BD2MXhvF2msbw%3D

    Article  CAS  Google Scholar 

  17. A Ribeiro-Silva LN Zambelli Ramalho S Britto Garcia S Zucoloto (2003) ArticleTitleThe relationship between p63 and p53 expression in normal and neoplastic breast tissue Arch Pathol Lab Med 3 336–340

    Google Scholar 

  18. MP Foschini A Gaiba R Cocchi MG Pennesi MR Gatto GP Frezza A Pession (2004) ArticleTitlePattern of p63 expression in squamous cell carcinoma of the oral cavity Virchows Arch 4 332–339 Occurrence Handle10.1007/s00428-003-0969-x Occurrence Handle1:CAS:528:DC%2BD2cXivV2jsrw%3D

    Article  CAS  Google Scholar 

  19. LD Davis W Zhang A Merseburger et al. (2002) ArticleTitleP63 expression profile in normal and malignant prostate epithelial cells Anticancer Res 22 3819–3825 Occurrence Handle1:CAS:528:DC%2BD3sXhtFGntLg%3D Occurrence Handle12553000

    CAS  PubMed  Google Scholar 

  20. M Tsujita-Kyutoku K Kiuchi N Danbara T Yuri H Senzaki A Tsubura (2003) ArticleTitleP63 expression in normal human epidermis and epidermal appendages and their tumors J Cutan Pathol 1 11–17 Occurrence Handle10.1034/j.1600-0560.2003.300102.x

    Article  Google Scholar 

  21. BY Wang J Gil D Kaufman L Gan DS Kohtz DE Burstein (2002) ArticleTitleP63 in pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors Hum Pathol 9 921–926 Occurrence Handle10.1053/hupa.2002.126878 Occurrence Handle1:CAS:528:DC%2BD38XotlGgsLk%3D

    Article  CAS  Google Scholar 

  22. JS Reis-Filho B Torio A Albergaria FC Schmitt (2002) ArticleTitleP63 expression in normal skin and usual cutaneous carcinomas J Cutan Pathol 9 517–523 Occurrence Handle10.1034/j.1600-0560.2002.290902.x

    Article  Google Scholar 

  23. JN Glickman A Yang A Shahsafaei F McKeon RD Odze (2001) ArticleTitleExpression of p53-related protein p63 in the gastrointestinal tract and in esophageal metaplastic and neoplastic disorders Hum Pathol 11 1157–1165 Occurrence Handle10.1053/hupa.2001.28951

    Article  Google Scholar 

  24. A Tannapfel S Schmelzer M Benicke et al. (2001) ArticleTitleExpression of the p53 homologues p63 and p73 in multiple simultaneous gastric cancer J Pathol 2 163–170 Occurrence Handle10.1002/path.947

    Article  Google Scholar 

  25. Y Ito T Takeda K Wakasa M Tsujimoto M Sakon N Matsuura (2001) ArticleTitleExpression of p73 and p63 proteins in pancreatic adenocarcinoma: p73 overexpression is inversely correlated with biological aggressiveness Int J Mol Med 1 67–71

    Google Scholar 

  26. JT O'Connell GL Mutter A Cviko et al. (2001) ArticleTitleIdentification of a basal/reserve cell immunophenotype in benign and neoplastic endometrium: a study with the p53 homologue p63 Gynecol Oncol 1 30–36 Occurrence Handle10.1006/gyno.2000.6026

    Article  Google Scholar 

  27. PA Hall AC Woodman SJ Campbell NA Shepherd (2001) ArticleTitleExpression of the p53 homologue p63alpha and DeltaNp63alpha in the neoplastic sequence of Barrett's oesophagus: correlation with morphology and p53 protein Gut 5 618–623 Occurrence Handle10.1136/gut.49.5.618

    Article  Google Scholar 

  28. R Parsa A Yang F McKeon H Green (1999) ArticleTitleAssociation of p63 with proliferative potential in normal and neoplastic human keratinocytes J Invest Dermatol 6 1099–1105 Occurrence Handle10.1046/j.1523-1747.1999.00780.x

    Article  Google Scholar 

  29. A Yang M Kaghad Y Wang et al. (1998) ArticleTitleP63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities Mol Cell 3 305–316 Occurrence Handle10.1016/S1097-2765(00)80275-0

    Article  Google Scholar 

  30. P Visca PL Alo F Nonno ParticleDel et al. (1999) ArticleTitleImmunohistochemical expression of fatty acid synthase, apoptotic-regulating genes, proliferating factors, and ras protein product in colorectal adenomas, carcinomas, and adjacent nonneoplastic mucosa Clin Cancer Res 12 4111–4118

    Google Scholar 

  31. A Yamaguchi Y Kurosaka S Fushida M Kanno Y Yonemura K Miwa I Miyazaki (1992) ArticleTitleExpression of p53 protein in colorectal cancer and its relationship to short-term prognosis Cancer 12 2778–2784

    Google Scholar 

  32. E Campo O Calle-Martin ParticleDe la R Miquel et al. (1991) ArticleTitleLoss of heterozygosity of p53 gene and p53 protein expression in human colorectal carcinomas Cancer Res 16 4436–4442

    Google Scholar 

  33. G Lanza SuffixJr I Maestri A Dubini R Gafa A Santini S Ferretti L Cavazzini (1996) ArticleTitleP53 expression in colorectal cancer: relation to tumor type, DNA ploidy pattern and short-term survival Am J Clin Pathol 5 604–612

    Google Scholar 

  34. M Serrano GJ Hannon D Beach (1993) ArticleTitleA new regulatory motif in cell cycle control causing specific inhibition of cyclin D/CDK4 Nature 366 704–707 Occurrence Handle10.1038/366704a0 Occurrence Handle1:CAS:528:DyaK2cXhsFOgu7Y%3D Occurrence Handle8259215

    Article  CAS  PubMed  Google Scholar 

  35. T Tada T Watanabe S Kazama T Kanazawa K Hata Y Komuro H Nagawa (2003) ArticleTitleReduced p16 expression correlates with lymphatic invasion in colorectal cancers Hepatogastroenterology 54 1756–1760

    Google Scholar 

  36. CY Dai EE Furth R Mick J Koh T Takayama Y Niitsu GH Enders (2000) ArticleTitleP16 expression begins early in human colon neoplasia and correlates inversely with markers of cell proliferation Gastroenterology 119 929–942 Occurrence Handle10.1053/gast.2000.7952 Occurrence Handle1:CAS:528:DC%2BD3cXnvV2gsr4%3D Occurrence Handle11040180

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

The authors thank Auristela de Mello Martins for technical assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Leandra Náira Zambelli Ramalho M.D., Ph.D..

About this article

Cite this article

Carneiro, F.P., Ramalho, L.N.Z., Britto-Garcia, S. et al. Immunohistochemical Expression of p16, p53, and p63 in Colorectal Adenomas and Adenocarcinomas. Dis Colon Rectum 49, 588–594 (2006). https://doi.org/10.1007/s10350-006-0515-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10350-006-0515-4

Key words

Navigation