Selected morphologic features influencing the prognosis of conventional renal cell carcinomas co-expressing P53 and MDM2

Abstract

Renal cell carcinoma is the most deadly of common urologic malignancies. The classical prognostic factors, including tumor type, grade and stage, as well as performance status of the patient, offer important information, but there is a need for new biomarkers which could improve the quality of prognostication. It has been proposed that tumors co-expressing P53 and MDM2 could represent a specific, more aggressive subgroup. The aim of the study was to explore this hypothesis using tissue microarrays, using two different anti-P53 antibodies. The material analyzed consisted of 470 cases of renal clear cell carcinoma. Reaction for P53 was positive in 15.1 or 13.2% of cases, depending on the antibody used. Reaction for MDM2 was positive in 37.9% of cases; 6.5 or 5.3% of cases coexpressed P53 and MDM2. Both P53-positive and double P53/MDM2-positive cases were higher grade and more likely to contain a sarcomatoid component, but their stage was similar to negative cases. PAb1081 P53-positive MDM2-positive cases were larger than the rest of the tumors (7.6 cm vs. 6.1 cm, p < 0.001). Our data support the hypothesis of prognostic significance of P53, and double P53/MDM2 positivity, yet further studies are needed to clarify the issue.

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2

“…There were 31 cases (6.6%) positive for both P53 and MDM2 using the DO-7 antibody, and 25 cases (5.3%) when using the PAb1081 antibody. Further details with respect to the histopathologic characteristics and their relationship with P53 and MDM2 expression may be found in our previous work [2]. The mean percentage of Ki-67 positive cells was 0.6% (range 0 to 33% SD 2.6).…”

“…It has been hypothesized that RCCs expressing both P53 and MDM2 behave in a more aggressive fashion [1,10,11]. We decided to further explore this idea and in our previous work [2] we found a number of morphologic differences between P53/MDM2-positive and -negative CCRCC, which could influence the prognosis of this subgroup of tumors.…”

“…It has been suggested that co-expression of P53 and MDM2 may define a distinct group of CCRCCs [1]. In our previous work [2] we explored this hypothesis by comparing the histologic prognostic factors such as stage, grade or presence of necrosis in tumors with or without doubly-expressed P53 and MDM2. The aim of the current study is to analyze the expression of potential immunohistochemical markers including Ki-67, VEGF-A, VEGF-C, VEGF-D, GLUT1, CK 7 and CA9 in samples expressing both P53 and MDM2, and to determine whether these immunohistochemical markers have prognostic significance.…”

Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects

“…However, a minimum proportion of rhabdoid features in the total tumor volume is unnecessary for diagnostic purposes. Recently, the expression of p53, AEG-1 and MDM2 may be associated with tumor progression or prognosis [53,54]. Therefore, it may be interesting to study the expression of p53, AEG-1 and MDM2 in RCC with rhabdoid features.…”