MDM2 Hyperploidy and Monoploidy in Urothelial Carcinoma May Have Diagnostic and Prognostic Significance
AF Liang, R Dhir, S Bastacky, A Perepletchikov, AV Parwani. University of Pittsburgh Medical Center, Pittsburgh, PA
Background: The protein MDM2 is a negative regulator of the tumor suppressor p53, and appears to exert effects on RB and E2f as well. Overexpression of MDM2 has been implicated in many human tumors, including epithelial and mesenchymal neoplasms of various organ systems. Additionally, MDM2 is regarded as a marker of prognosis, with increased expression being related to higher stage and propensity for metastases. In the current study, the expression of MDM2 as it relates to different grades and stages of urothelial carcinoma is analyzed.
Design: A series of urothelial neoplasms is selected, which include one inverted papilloma, one papilloma, six low grade (LG) urothelial carcinomas (UC), one LG UC with invasion, one LG UC with focal high grade (HG) component, three LG UC with focal HG and microinvasion, two HG UC with microinvasion, seven HG UC with frank invasion, and five HG UC without invasion, totalling 27 cases. Fluorescent in-situ hybridization (FISH) for the MDM2 gene was performed on unstained blanks. Immunohistochemistry (IHC) for p53 was performed on the same tissue section as FISH. A minimum of 60 cells were counted for FISH, and the IHC results were scored from 0 to 3, with 3 representing most intensity and quantity of staining.
Results: Of the 25 cases with urothelial carcinoma, four (16%) have greater than 20% hyperploidy for MDM2 (the cut-off for significance). These cases include one LG UC with focal HG and microinvasion, one HG UC without invasion, and two HG UC with invasion. Of the same cases, four (16%) have greater than 50% monosomy for MDM2 (the cut-off for significance). These cases include two LG UC, one HG UC with microinvasion, and one HG UC with invasion. IHC results with p53 do not necessarily correspond with MDM2 results, as strong staining was seen in cases of UC with hyperploidy, and absent/weak staining was seen in cases of hypoploidy.
Conclusions: The MDM2 results seen in these cases of urothelial carcinoma support previous observations in other organ systems that hyperploidy is seen in more advanced neoplasms with higher stage. The observation of hypoploidy in UC is novel, and the relationship between tumorigenesis and hypoploidy is still being evaluated. The lack of significant correlation between p53 and MDM2 indicates the likelihood of other factors affecting p53 expression in UC neoplasia.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 137, Wednesday Afternoon