Predictive value of p53 and pRb expression in superficial bladder cancer patients treated with BCG and interferon‐alpha

Abstract

BACKGROUNDNuclear 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‐α).METHODSA prospective histological review was performed for 80 superficial bladder transitional cell carcinoma patients who underwent postresection intravesical regimes of BCG (81mg, n = 33 or 27 mg, n = 20) or BCG (27 mg) with IFN‐α (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.RESULTSpRb 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‐α (BCG + IFN‐α) 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‐α with respect to recurrence, progression, or cancer‐specific death.CONCLUSIONSNuclear pRb underexpression may be predictive of nonresponse and cancer recurrence after intravesical BCG + IFN‐α 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‐α therapy. Cancer 2007. © 2007 American Cancer Society.

Loss of heterozygosity for Rb locus and pRb immunostaining in laryngeal cancer: a clinicopathologic, molecular and immunohistochemical study.

“…The clinical relevance of pRb expression in human tumours is still controversial: low levels of this protein have been found to correlate with a worse prognosis in prostate, breast, endometrial, head and neck cancer but not in bladder and gastric cancers [10,19,20,[25][26][27][28]. In these data the loss of pRb protein was observed in 9/67 cases (13.4) and was significantly correlated with T status (p=0.03) and local recurrence (p=0.035).…”

Immunohistochemical characterization of urothelial carcinoma

“…The CK7 and CK20 antigen staining was recommended for differential diagnostic of low-differentiated carcinomas in order to distinguish their adenomatous versus squamous cell origin (40). The CK7 and p63 antigen staining along with the detection of high molecular cytokeratin (HMWCK/clone 34βE12) were frequently applied to recognize the invasively growing HG UCs in males from their non-differentiated prostatic counterparts (20,31,50).…”

Management of BCG Failures in Non-Muscle-Invasive Bladder Cancer

“…Some investigators reported that P53 and Ki-67 protein overexpression are independent predictors for recurrence in NMIBC treated with BCG [23,24], but others have reported no significant associations [25][26][27][28]. The results for ezrin protein expression were similarly inconsistent [24,27,29].…”

“…The results for ezrin protein expression were similarly inconsistent [24,27,29]. Recently, pRb was proposed as a predictive factor of nonresponse and recurrence after BCG plus IFN-α [28]. However, because these markers have not been confirmed by a prospective study, debate about these issues remains.…”