Expression of cell-cycle regulatory proteins and their prognostic value in superficial low-grade urothelial cell carcinoma of the bladder.
OBJECTIVE
Cell-cycle regulatory proteins are important indicators in determining progression trough the cell-cycle and progression to invasive cancer in patients presenting with superficial bladder cancer. We performed an immunohistochemical study in order to evaluate the prognostic value of the expression of p16, p27, pRb, p53 and Ki-67 in superficial grade I and II papillary urothelial cell carcinoma of the bladder.


METHODS
p16, p27, p53, pRb and Ki-67 immunoexpression was studied in 14 pTa, 35 pT1a and 7 pT1b bladder tumours at presentation and at recurrence of their tumours. The recurrence-free survival and the progression-free survival were analysed according to these regulatory cell-cycle proteins expression.


RESULTS
For survival in univariate analysis a high Ki-67 labelling index was a poor prognostic factor for recurrence-free and progression-free survival (P=0.0014 and P=0.012, respectively). Ki-67 labelling index was also an independent recurrence-free survival prognostic factor (P=0.0005). The p16, p27, p53 and pRb immunoreactivity was not significantly associated with recurrence or progression rate in this group of bladder carcinomas.


CONCLUSIONS
These data suggest that the Ki-67 labelling index can be a reliable marker in predicting recurrence and/or progression in superficial low-grade bladder carcinomas and may be relevant in planning adjuvant therapy.
Santos
L L
LL
Surgical Oncology Department, Portuguese Institute of Oncology, Rua Dr Bernardino de Almeida, 4200 Porto, Portugal. ucib@ipoporto.min-saude.pt
Amaro
T
T
Pereira
S A
SA
Lameiras
C R
CR
Lopes
P
P
Bento
M J
MJ
Oliveira
J
J
Criado
B
B
Lopes
C S
CS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005656:Fungal Proteins; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D009367:Neoplasm Staging; D011174:Portugal; D011379:Prognosis; D012697:Serine Endopeptidases / Q000096:biosynthesis; D012720:Severity of Illness Index; D012737:Sex Factors; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D019459:Urothelium / Q000378:metabolism*
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D005656:Fungal Proteins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D012697:Serine Endopeptidases