p53, pRb, Cyclin D1 and HER2 Expression in a Heterogeneous Cystectomy Cohort
Luciana Schultz, Samuel JT Spagnul, Stephania M Bezerra, Gilcy R Damm, Thais S Giuliangelis, Walter H da Costa, Gustavo C Guimaraes, Fernando A Soares, Isabela W da Cunha. Antonio Prudente Foundation, São Paulo, Brazil; AC Camargo Hospital, São Paulo, Brazil
Background: Invasive urothelial carcinoma still carries a high mortality rate. Hence, reproducible and clinically useful prognostic markers are needed for better patient stratification. p53, pRb, cyclin D1 and HER2 are implicated in progression and invasive behavior in urothelial carcinoma. We investigated immunohistochemical expression of these markers and correlated with pathological stage and outcome.
Design: Slides and paraffin blocks were retrieved from 98 patients with urothelial carcinoma treated by cystectomy at our institution (2000-2010). Immunohistochemistry was performed for each marker on TMA and whole slides. Pathological stage (pT) was categorized as Superficial (pTis/pTa/pT1; n=18), Muscle-invasive (pT2; n=22) and non-Organ Confined (non-OC) (pT3/pT4; n=58). For each marker cut-offs for altered expression were defined based on comparison to corresponding benign urothelial controls. Outcome data was available in 88 patients as disease specific survival (DSS), overall survival (OS) and progression.
Results: Mean patient age was 66y (34-90) and M:F ratio was 1.85. Pre-operative BCG treatment was rendered in 16/78 (20%) patients. Altered expression of p53, pRb, cyclin D1 and HER2 was seen in 39 (39%), 21 (21%), 39 (39%) and 18 (18%) tumor samples, respectively. Markers within the same pathway significantly correlated: pRb with cyclin D1 and p53 which in turn correlated with HER2 (rr 0.2-0.3; p<0.03). Pathological stage was predictive of all outcome parameters. Abnormal expression of pRb and cyclin D1 associated with non-OC disease (p=0.05 and p=0.0001, respectively). Co-alteration of p53 and pRb was present in 14 tumors, 12 of which were non-OC (p=0.02). OS, DSS and progression rate were 46%, 67% and 37%, respectively (mean FU of 52,2mo). pRb loss was a predictor of OS in superficial tumors (p=0.02) while p53 showed a trend towards progression (p=0.08) but no marker was predictive of DSS.
Conclusions: All markers were altered in urothelial carcinoma compared to benign controls. Proteins within the same pathway were well correlated. Although high cyclin D1 expression and pRb loss were significantly more frequent in non-OC disease, prognostic value was limited in our cohort.
Category: Genitourinary (including renal tumors)
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 100, Tuesday Morning