The prognostic value of p73 overexpression in colorectal carcinoma: a clinicopathologic, immunohistochemical, and statistical study of 204 patients.
BACKGROUND
The protein p73 is the first identified homolog of the tumor suppressor gene p53, but its function in tumor development has not been established. Indeed, the results regarding the p73 implication in colorectal cancers is still controversial.


OBJECTIVE
We investigated whether the p73 is implicated in colorectal cancer, whether the p73 expression is related to prognosis and whether the p73 expression is correlated with p21-ras or p53.


METHODS
We performed a comparative immunohistochemical analysis of p73, p53, and p21ras proteins in primary colorectal tumor with matched normal mucosa and metastasis from 204 patients with colorectal cancer. We correlated these expressions with clinicopathologic variables and we compared the different profiles between nonmucinous carcinoma and mucinous carcinoma.


RESULTS
In this study, we did not find any correlation between p73 expression, sex, age, site, differentiation and stage. Overexpression of p73 was significantly correlated with infiltrating growth pattern (P<0.0001) and nonmucinous carcinoma (P<0.0001). Furthermore, frequency and intensity of p73 expression were marquedly increased from normal mucosa (26%), to primary tumors (75%) and to metastasis (97%). Furthermore, expression of p73 was also correlated with shorter survival period. The prognostic significance of p73 expression remained, even after adjustment for the clinical and pathologic variables. The p73 expression was positively correlated only with p21ras expression (P<0.0001).


CONCLUSIONS
All these findings prove that p73 expression should be considered as a valuable poor prognostic marker. Our data also suggest that TP73 gene may play a role in colorectal carcinoma development.
Toumi
Amira Arfaoui
AA
Laboratory of Colorectal Cancer Research UR03ES04, Science University Tunis, Tunis, Tunisia. arfaouiamira@hotmail.com
El Hadj
Olfa El Amine
Oel A
Ben Mahmoud
Lilia Kriaa
LK
Ben Hmida
Abd El Majid
Ael M
Chaar
Ines
I
Gharbi
Lasaad
L
Mzabi
Sabeh
S
Bouraoui
Saadia
S
D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology / Q000556:secondary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)