Comparison of mTORC1 Pathway Immunoexpression between Chromophobe Renal Cell Carcinoma and Renal Oncocytoma
Jessica Z Sugianto, Dinesh Rakheja, Ramy F Youssef, Yair Lotan, Vitaly Margulis, Theresa Kinard, Payal Kapur. University of Texas Southwestern Medical Center, Dallas, TX
Background: The mammalian target of rapamycin complex 1 (mTORC1) pathway is dysregulated in many human cancers, and agents targeting the mTORC1 are being clinical used. The mTORC1 pathway interacts with effectors of cell cycle progression and ultimately regulates protein translation and cell proliferation. We undertook this study to ascertain if there are any differences in the expression of mTORC1/ PI3K/AKT pathway components between chromophobe renal cell carcinoma (ChRCC) and renal oncocytoma (RO).
Design: Standard immunohistochemical analysis was performed for p-S6, p-mTOR, p-4EBP1, HIF-1a, p-AKT, and PI3K on sections of tissue microarrays constructed from 43 primary ChRCC and 51 primary RO treated at our hospital with nephrectomy (1998-2008). Duplicate 1.0 mm cores of representative tumor were obtained from each case to construct the tissue microarrays. Cytoplasmic expression was assessed for each marker as the percentage of positive cells (0-3) and intensity of staining (0-3). A final Histo-score was calculated as the product of intensity and percentage and correlated with clinic-pathologic parameters.
Results: The M:F ratio was 1.0 and 4.7, mean age at diagnosis was 55.3 and 64.9 years, and mean tumor size was 7.0 and 3.8 cm respectively for ChRCC and RO. Compared to normal proximal renal tubules, ChRCC showed increased expression of p-S6 in 6 (14.0%), p-mTOR in 28 (65.1%), p-4EBP1 in 14 (32.6%), HIF-1a in 41 (95.3%), PI3K in 12 (27.9%), and p-AKT in 13 (30.2%) cases. RO showed increased expression of p-S6 in 4 (7.8%), p-mTOR in 39 (78.0%), p-4EBP1 in 12 (24.0%), HIF-1a in 51 (100%), PI3K in 40 (80.0%), and p-AKT in 32 (64.0%) cases. There was significantly higher expression of PI3K (P <0.0001) and p-AKT (P=0.0017) in RO compared to ChRCC.
Conclusions: Our results indicate differential immunoexpression of PI3K and p-AKT in RO compared to ChRCC, indicating a difference in activation of PI3K/AKT signaling between the tumors.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 167, Monday Morning