Increasing Levels of a Mitochondrial Protein Marker Accompany Prostatic Carcinogenesis
CL Ellis, TC Cornish, C Koh, JL Hicks, B Gurel, AM De Marzo. The Johns Hopkins University School of Medicine, Baltimore, MD
Background: Mitochondrial DNA (mtDNA) copy number changes are commonly found in human cancers. In prostatic adenocarcinoma (CaP), studies evaluating mtDNA content have reported mixed results. The purpose of this study was use immunohistochemistry (IHC) and image analysis to determine whether increased mitochondria accompany prostatic carcinogenesis.
Design: Using a commercial antibody that recognizes mitochondria by IHC (MTC02, Abcam), we examined tissue microarrays (TMAs) from radical prostatectomies containing normal prostate tissue (253 cores from 59 patients), atrophy (129 cores from 28 patients), PIN (130 cores from 38 patients) and CaP (75 cores from 38 patients) using the TMAJ/FrIDA image analysis program. Since MYC has been shown to stimulate mitochondrial biogenesis, we correlated the expression levels with MYC protein from the same TMAs. The Gleason score ranged from 5-9 and pathological stages ranged from organ confined (OC) (T2N0Mx) to locally metastatic disease (T3BN1Mx).
Results: Image analysis revealed an increase in the intensity of staining (MitoInt) in focal atrophy (121.9; p= 0.0001), PIN (123.5, p=0.0001) and CaP (118.6, p=0.001) when compared to matched normal (107.7). Overall mitochondrial area per total nuclear area (MitoRatio) showed a stepwise increase in the median values going from atrophy (0.56, p=0.66), to PIN (1.06, p=0.0001), to CaP (1.39, p=0.0001) as compared to normal (0.41).
There was an increase in the MitoRatio from 1.26 for Gleason scores 5-6 to 1.68 for Gleason score 7-10. There was no difference in the MitoInt when stratified by Gleason score. In terms of stage, there was an increase in both the MitoRatio (1.37 for OC to 1.53 for non-OC; p= 0.98) and MitoInt (113.9 for OC to 129.4 for non-OC; p=0.03). There was no correlation between the overall levels of MYC staining and levels of MitoInt or MitoRatio. Similar staining results were obtained using a separate mitochondrial antibody (prohibin).
Conclusions: There is an increase in staining for a highly specific mitochondrial maker in focal atrophy, PIN and CaP. The results suggest that alterations in mitochondrial number occur frequently and early during prostatic carcinogenesis.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 119, Monday Morning