Prognostic impact of p63 and p53 expression in upper urinary tract transitional cell carcinoma.
OBJECTIVE
To analyze p63 and p53 immunoreactivity of upper urinary tract transitional cell carcinoma with respect to prognosis. p63 is required for the differentiation of normal urothelium and is expressed in both non-neoplastic urothelium and transitional cell carcinoma of the bladder.


METHODS
A total of 53 upper urinary tract transitional cell carcinoma specimens were investigated immunohistochemically using a tissue microarray technique. p63 and p53 immunoreactivity was analyzed digitally with respect to associations with pT stage and grade and impact on disease-free survival.


RESULTS
p63 expression was detected in 51 (96.2%) of 53 cases. Normal expression (greater than 90% of tumor cell nuclei) was observed in 1 (4.5%) of 22 Stage pT3 compared with 13 (41.9%) of 31 Stage pT1-T2 tumors (P = 0.003) and 4 (16%) of 25 G3 compared with 10 (35.7%) of 28 G2 tumors (P = 0.13). p53 overexpression (more than 10% of tumor cell nuclei) was found in 10 (18.9%) of 53 cases, including 2 (6.5%) of 31 Stage pT1-T2 and 8 (36.4%) of 22 Stage pT3 (P = 0.011) and 0 of 28 G2 and 10 (40%) of 25 G3 tumors (P <0.001). Metastatic disease was observed in 14 (26.4%) of 53 patients, including none of 14 with normal p63 expression compared with 14 (35.9%) of 39 with decreased (less than 90% of tumor cell nuclei) p63 expression (P = 0.02) and 5 (50%) of 10 patients with p53 overexpression compared with 9 (20.9%) of 43 patients with p53-negative tumors (P = 0.01). Multivariate analysis proved Stage pT3 was the only independent prognostic factor.


CONCLUSIONS
Decreased p63 immunoreactivity and p53 overexpression were significantly associated with advanced tumor stages and poor prognosis. However, neither parameter was an independent prognostic factor in multivariate analysis.
Zigeuner
Richard
R
Department of Urology, University of Graz Medical School, Graz, Austria.
Tsybrovskyy
Oleksiy
O
Ratschek
Manfred
M
Rehak
Peter
P
Lipsky
Katja
K
Langner
Cord
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins; D018572:Disease-Free Survival; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000032:analysis*; D011379:Prognosis; D015534:Trans-Activators / Q000032:analysis*; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D025521:Tumor Suppressor Proteins; D001749:Urinary Bladder Neoplasms; D014571:Urologic Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D019459:Urothelium / Q000737:chemistry / Q000473:pathology
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins