Abstract 799: Clinical correlation of variable expression of extracellular matrix metalloprotease inducer in renal cell carcinoma: Analysis of a tissue microarray using immunostaining scores
Authors: Lipe Brea , Petrella Brenda , Gui Jiang , Wason Shaun , Schned Alan , Ernstoff Marc 
Published: February 2011

Abstract
Extracellular matrix metalloprotease inducer (EMMPRIN, E) is a glycoprotein involved in cell signaling. E is thought to be involved in tumor invasiveness via tumor-stromal interactions and homophilic interactions between tumor cells. E is known to be highly expressed on the surface of malignant tumors, including RCC.
We evaluated E expression on 77 patients with renal neoplasms, including 57 clear cell (CRCC), 9 chromophobe (ChRCC), 4 papillary (PRCC) carcinomas, 3 oncocytomas (OCC), 2 CRCC with sarcomatoid differentiation (SRCC), and 2 metastatic tumors using immunohistochemistry on a tissue microarray (TMA). The TMA included two samples of each tumor and an adjacent sample of normal parenchyma from each patient. The TMA was stained with goat anti-human E antibody specific for the extracellular domain of E (R&D Systems at 1:400 dilution). E staining was graded in both cytoplasmic and membranous domains for intensity on a 0-3 scale and for % staining in deciles from 0 to 100 percent. A final staining score was obtained for cytoplasm and membranes separately by multiplying the average intensity and % cells staining for each of the two tumor samples from each patient.
Our results show a mean membranous staining score of 134 +/- 10 and cytoplasmic score of 85 +/- 8 from the tumor tissues. Normal tissues showed a mean membranous score of 22 +/- 3 with a cytoplasmic score of 160 +/- 9. CRCC showed a statistically significant lower membranous and cytoplasmic score compared to other tissue types combined (120 +/- 13 & 71 +/- 9 vs. 171 +/- 20 & 125 +/- 13; p=0.029 &0.006, respectively). TNM stage I and II tumors (n=49) also showed a significantly lower membranous and cytoplasmic score compared to stage III and IV tumors (n=28) (110 +/- 11 & 66 +/- 9 vs. 174 +/- 18 & 119 +/- 14; p= 0.004 & 0.003). Fuhrman nuclear grades I and II (n=41) showed a statistically significant lower cytoplasmic score than grades III and IV (n=35) (58 +/- 9 vs. 106 +/- 11 p=0.003). Tumor size correlated with increasing E expression when E was treated as a continuous variable (membranous p=0.002; cytoplasmic p=0.01). A lower membranous and cytoplasmic E score was also seen in patients still alive after a mean follow up time of 6.3 years compared to patients who had died from all causes of mortality (108 +/- 14 vs. 155 +/- 14 & 64+/-11 vs. 103 +/- 11; p= 0.026 and p=0.020).
In summary, in cancerous tissues, membranous expression increases as cytoplasmic expression decreases relative to normal tissues. However, increased E expression in both membranes and cytoplasm was found to correlate with increased tumor size, stage, and decreased survival amongst tumor tissues. These data support variable expression of E throughout the course of malignancy. Further investigation is needed to understand the trafficking and regulatory mechanisms that may be responsible for this variable E expression.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 799.