Predictive value of p53 and pRb expression in superficial bladder cancer patients treated with BCG and interferon-alpha.
BACKGROUND
Nuclear p53 and retinoblastoma protein (pRb) were reported to be poor prognostic indicators for transitional cell carcinoma of the bladder. The authors sought to determine the prognostic value of nuclear p53 and pRb in superficial bladder transitional cell carcinoma patients who were treated with intravesical bacille Calmette-Guerin (BCG) or BCG with interferon-alpha (IFN-alpha).


METHODS
A prospective histological review was performed for 80 superficial bladder transitional cell carcinoma patients who underwent postresection intravesical regimes of BCG (81 mg, n = 33 or 27 mg, n = 20) or BCG (27 mg) with IFN-alpha (n = 27), and followed for a mean of 4.5 years. Hematoxylin and eosin (H & E) and immunoperoxidase staining were performed on tissue sections. Nuclear p53 and pRb immunoreactivity were assessed semiquantitatively, by using a combination of staining extent and intensity, to categorize overexpression or underexpression. Data were analyzed by using chi-square analysis, multiple logistic regression, and Kaplan-Meier curves.


RESULTS
pRb expression was not associated with patient outcome after BCG-alone therapy, but pRb underexpression was significantly associated with BCG nonresponse and tumor recurrence (P = .047) after BCG and IFN-alpha (BCG + IFN-alpha) therapy. Low-grade tumors were associated with pRb overexpression, with or without nuclear p53 underexpression (P = .019; P = .043, respectively). p53 expression alone or in combination with pRb expression had no significant relation with tumor response to BCG alone or BCG + IFN-alpha with respect to recurrence, progression, or cancer-specific death.


CONCLUSIONS
Nuclear pRb underexpression may be predictive of nonresponse and cancer recurrence after intravesical BCG + IFN-alpha therapy. Nuclear p53 expression or its combination with pRb expression is not associated with post-BCG clinical outcome, so p53 expression or p53 with pRb expression should not be used to influence decisions concerning BCG-alone or BCG + IFN-alpha therapy.
Esuvaranathan
Kesavan
K
Department of Surgery, National University of Singapore, Singapore. suresuva@nus.edu.sg
Chiong
Edmund
E
Thamboo
Thomas Paulraj
TP
Chan
Yiong Huak
YH
Kamaraj
Revathi
R
Mahendran
Ratha
R
Teh
Ming
M
D001500:BCG Vaccine / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000627:therapeutic use*; D011379:Prognosis; D016160:Retinoblastoma Protein / Q000032:analysis*; D013534:Survival; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology
D001500:BCG Vaccine; D016898:Interferon-alpha; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53