Prognostic significance of cyclin E and p53 protein overexpression in carcinoma of the renal pelvis and ureter.
Cyclin E gene alteration in the cell cycle plays an important role in carcinogenesis, while p53 protein affects different phase checkpoint pathways by activating p21WAF1/CIP1 in the normal cell cycle. We immunohistochemically examined the expression of cyclin E and p53 proteins in 121 patients with transitional cell carcinoma (TCC) of the renal pelvis and ureter to determine their significance for tumour behaviour and patient prognosis. Cyclin E and p53 immunostaining of the nucleus was observed in 36 tumours (29.8%) and 35 tumours (28.9%) respectively. A significant percentage, 69.4% (25 out of 36 tumours), of the cyclin E-positive tumours exhibited simultaneous labelling for p53 (P < 0.05). Mirror-section technique was performed in five selected double-positive tumours to identify cancer cells that were nuclei positive for both cyclin E and p53. The prevalence of cases simultaneously exhibiting both cyclin E and p53 immunostaining was higher in the high-grade tumours (P < 0.01) than in the other types of tumours. Patients with TCCs coexpressing cyclin E and p53 had a significantly poorer prognosis than those expressing neither cyclin E nor p53 (P < 0.001). These in vivo findings provide evidence for cyclin E protein overexpression in TCCs intimately associated with p53 alteration and suggest that simultaneous overexpression of both cyclin E and p53 is related to tumour behaviour and poor prognosis.
Furihata
M
M
Department of Pathology II, Kochi Medical School, Nankoku, Japan.
Ohtsuki
Y
Y
Sonobe
H
H
Shuin
T
T
Yamamoto
A
A
Terao
N
N
Kuwahara
M
M
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000378:metabolism / Q000401:mortality*; D002453:Cell Cycle; D015331:Cohort Studies; D019927:Cyclin E / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007682:Kidney Pelvis; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D014516:Ureteral Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality*
D014408:Biomarkers, Tumor; D019927:Cyclin E; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53