p63 is highly expressed in some malignant tumors and is associated with tumorigenesis, invasion and metastasis. The aim of our study was to evaluate the clinical significance of p63 in colorectal cancer (CRC). p63 expression was detected by immunohistochemistry in 66 CRC patients. Correlations between p63 expression and clinicopathological factors, progression-free survival (PFS) and overall survival (OS) were analyzed. Among the 66 CRC cases, 31 cases (47%) exhibited a high score of p63 expression, while 35 cases (53%) were marked with a low score. The p63 level correlated with peritumoral deposits (p=0.021). The 5-year OS rates in the low p63 score and high p63 score groups were, respectively, 49% and 74% (p<0.001). The 5-year PFS rates in the low p63 score and high p63 score groups were, respectively, 44% and 71% (p<0.001). Univariate analysis revealed that p63 expression was correlated with OS and PFS. Multivariate analysis suggested that p63 expression was an independent prognostic factor for OS (p=0.035). In conclusion, p63 was negatively correlated with peritumoral deposits and positively associated with OS and PFS in CRC. The data suggest that p63 is a potential prognostic factor for CRC.
SiegelR., WardE., BrawleyO., JemalA.. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths.CA Cancer J Clin2011; 61: 212–36.
2.
Reproductive health through community involvement with special attention to adolescents and clinical contraception.RAS/98/P63.Adolesc Educ Newsl1999; 2: 6.
3.
MillsA.A., ZhengB., WangX.J., VogelH., RoopD.R., BradleyA.. p63 is a p53 homologue required for limb and epidermal morphogenesis.Nature1999; 398: 708–13.
4.
YangA., KaghadM., WangY.. p63, a p53 homolog at 3q27–29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities.Mol Cell1998; 2: 305–16.
5.
HankerL., KarnT., RuckhaeberleE.. Clinical relevance of the putative stem cell marker p63 in breast cancer.Breast Cancer Res Treat2010; 122: 765–75.
6.
YangC., HayashidaT., ForsterN.. The integrin alpha(v) beta(3–5) ligand MFG-E8 is a p63/p73 target gene in triple-negative breast cancers but exhibits suppressive functions in ER(+) and erbB2(+) breast cancers.Cancer Res2010; 71: 937–45.
7.
GudlaugssonE., SkalandI., UndersrudE., JanssenE.A., SoilandH., BaakJ.P.. D2–40/p63 defined lymph vessel invasion has additional prognostic value in highly proliferating operable node negative breast cancer patients.Mod Pathol2011; 24: 502–11.
8.
MukhopadhyayS., KatzensteinA.L.. Subclassification of non-small cell lung carcinomas lacking morphologic differentiation on biopsy specimens: utility of an immunohistochemical panel containing TTF-1, napsin A, p63, and CK5/6.Am J Surg Pathol2011; 35: 15–25.
9.
UramotoH., YamadaS., HanagiriT.. Immunohistochemical staining with deltaNp63 is useful for distinguishing the squamous cell component of adenosquamous cell carcinoma of the lung.Anticancer Res2010; 30: 4717–20.
10.
IaconoM.L., MonicaV., SaviozziS.. p63 and p73 isoform expression in non-small cell lung cancer and corresponding morphological normal lung tissue.J Thorac Oncol2011; 6: 473–81.
11.
Karni-SchmidtO., Castillo-MartinM., ShenT.H.. Distinct expression profiles of p63 variants during urothelial development and bladder cancer progression.Am J Pathol2011; 178: 1350–60.
12.
UristM.J., Di ComoC.J., LuM.L.. Loss of p63 expression is associated with tumor progression in bladder cancer.Am J Pathol2002; 161: 1199–206.
13.
DhillonP.K., BarryM., StampferM.J.. Aberrant cytoplasmic expression of p63 and prostate cancer mortality.Cancer Epidemiol Biomarkers Prev2009; 18: 595–600.
14.
ParsonsJ.K., SariaE.A., NakayamaM.. Comprehensive mutational analysis and mRNA isoform quantification of TP63 in normal and neoplastic human prostate cells.Prostate2009; 69: 559–69.
15.
KalebiA., HaleM.. p63 expression in ovarian tumours: immunopositivity in metastatic transitional cell carcinoma of the ovary.Histopathology2008; 53: 228.
16.
Hallack NetoA.E., SiqueiraS.A., DulleyF.L., RuizM.A., ChamoneD.A., PereiraJ.. p63 protein expression in high risk diffuse large B-cell lymphoma.J Clin Pathol2009; 62: 77–9.
17.
GualcoG., WeissL.M., BacchiC.E.. Expression of p63 in anaplastic large cell lymphoma but not in classical Hodgkin's lymphoma.Hum Pathol2008; 39: 1505–10.
18.
ZuoX.L., ZhouY., ZhouX.. [Expression of survivin and P63 protein in B cell non-Hodgkin's lymphoma and their effects on cell apoptosis and proliferation].Zhongguo Shi Yan Xue Ye Xue Za Zhi.2007; 15: 99–102.
19.
GundersonL.L., JessupJ.M., SargentD.J., GreeneF.L., StewartA.K.. Revised TN categorization for colon cancer based on national survival outcomes data.J Clin Oncol2010; 28: 264–71.
20.
GoldsteinN.S., TurnerJ.R.. Pericolonic tumor deposits in patients with T3N+MO colon adenocarcinomas: markers of reduced disease free survival and intra-abdominal metastases and their implications for TNM classification.Cancer2000; 88: 2228–38.
21.
PuppaG., MaisonneuveP., SonzogniA.. Pathological assessment of pericolonic tumor deposits in advanced colonic carcinoma: relevance to prognosis and tumor staging.Mod Pathol2007; 20: 843–55.
22.
LoD.S., PollettA., SiuL.L., GallingerS., BurkesR.L.. Prognostic significance of mesenteric tumor nodules in patients with stage III colorectal cancer.Cancer2008; 112: 50–4.
23.
UenoH., MochizukiH., HashiguchiY.. Extramural cancer deposits without nodal structure in colorectal cancer: optimal categorization for prognostic staging.Am J Clin Pathol2007; 127: 287–94.
24.
UenoH., MochizukiH.. Clinical significance of extrabowel skipped cancer infiltration in rectal cancer.Surg Today1997; 27: 617–22.
25.
MassionP.P., TaflanP.M., Jamshedur RahmanS.M.. Significance of p63 amplification and overexpression in lung cancer development and prognosis.Cancer Res2003; 63: 7113–21.
26.
TakahashiY., NoguchiT., TakenoS., KimuraY., OkuboM., KawaharaK.. Reduced expression of p63 has prognostic implications for patients with esophageal squamous cell carcinoma.Oncol Rep2006; 15: 323–8.
27.
KogaF., KawakamiS., FujiiY.. Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder.Clin Cancer Res2003; 9: 5501–7.
28.
ParkB.J., LeeS.J., KimJ.I.. Frequent alteration of p63 expression in human primary bladder carcinomas.Cancer Res2000; 60: 3370–4.
29.
FukushimaH., KogaF., KawakamiS.. Loss of DeltaNp63alpha promotes invasion of urothelial carcinomas via N-cadherin/Src homology and collagen/extracellular signal-regulated kinase pathway.Cancer Res2009; 69: 9263–70.
30.
ZigeunerR., TsybrovskyyO., RatschekM., RehakP., LipskyK., LangnerC.. Prognostic impact of p63 and p53 expression in upper urinary tract transitional cell carcinoma.Urology2004; 63: 1079–83.
31.
KommaganiR., LeonardM.K., LewisS., RomanoR.A., SinhaS., KadakiaM.P.. Regulation of VDR by deltaNp63alpha is associated with inhibition of cell invasion.J Cell Sci2009; 122: 2828–35.
32.
BarbieriC.E., TangL.J., BrownK.A., PietenpolJ.A.. Loss of p63 leads to increased cell migration and up-regulation of genes involved in invasion and metastasis.Cancer Res2006; 66: 7589–97.
33.
FloresE.R.. The roles of p63 in cancer.Cell Cycle2007; 6: 300–4.
34.
WuG., NomotoS., HoqueM.O.. DeltaNp63alpha and TAp63alpha regulate transcription of genes with distinct biological functions in cancer and development.Cancer Res2003; 63: 2351–7.
35.
BoldrupL., CoatesP.J., GuX., NylanderK.. DeltaNp63 isoforms differentially regulate gene expression in squamous cell carcinoma: identification of Cox-2 as a novel p63 target.J Pathol2009; 218: 428–36.
36.
GhioniP., BologneseF., DuijfP.H., Van BokhovenH., MantovaniR., GuerriniL.. Complex transcriptional effects of p63 isoforms: identification of novel activation and repression domains.Mol Cell Biol2002; 22: 8659–68.
37.
NekulovaM., HolcakovaJ., CoatesP., VojtesekB.. The role of p63 in cancer, stem cells and cancer stem cells.Cell Mol Biol Lett2011; 16: 296–327.
38.
GuoX., KeyesW.M., PapazogluC.. TAp63 induces senescence and suppresses tumorigenesis in vivo.Nat Cell Biol2009; 11: 1451–7.
39.
GressnerO., SchillingT., LorenzK.. TAp63alpha induces apoptosis by activating signaling via death receptors and mitochondria.EMBO J2005; 24: 2458–71.
40.
SunR., ZhangY., LvQ.. Toll-like receptor 3 (TLR3) induces apoptosis via death receptors and mitochondria by up-regulating the transactivating p63 isoform alpha (TAP63alpha).J Biol Chem2011; 286: 15918–28.
41.
ComptonC.C., FieldingL.P., BurgartL.J.. Prognostic factors in colorectal cancer. College of American Pathologists Consensus Statement 1999.Arch Pathol Lab Med2000; 124: 979–94.
