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.
Similar content being viewed by others
References
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Acknowledgment
The authors thank Auristela de Mello Martins for technical assistance.
Author information
Authors and Affiliations
Corresponding author
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
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10350-006-0515-4