Dysregulation of mTOR Pathway in Plasmacytoid Variant of Urothelial Carcinoma of the Urinary Bladder
Nilda D Gonzalez-Roibon, Alcides Chaux, Adeboye O Osunkoya, Turki Al-Hussain, Jessica Hicks, Jonathan I Epstein, George J Netto. The Johns Hopkins University SOM, Baltimore, MD; Emory University SOM, Atlanta, GA
Background: Mammalian target of rapamycin (mTOR) pathway plays an important role in cell growth, migration, and proliferation. mTOR pathway dysregulation has been linked to oncogenesis in several malignancies, including conventional urothelial carcinoma of bladder. Several antineoplastic agents targeting mTOR pathway are currently available. Plasmacytoid variant of urothelial carcinoma (UC) is a rare but aggressive variant of bladder cancer. The current study assesses mTOR pathway status as well as c-myc and p27 expression, two markers known to interact with this pathway.
Design: Nineteen cases of plasmacytoid UC were retrieved from the surgical pathology files of our 2 institutions, including 12 cases from the consultation service of 2 of the authors. Whole sections were evaluated for immunoexpression of PTEN, phosphorylated mTOR (phos-mTOR), phosphorylated AKT (phos-AKT), phosphorylated S6 (phos-S6), c-myc, and p27. Antibody sources and IHC parameters were as previously described (Cancer 2010;116:5517). Cases with >10% loss of cytoplasmic PTEN expression were considered to show loss of PTEN. For the remaining markers, expression intensity (0 to 3+) and extent (0%–100%) was evaluated in each tumor. An H-Score (∑ intensity X percentage) was calculated. Pairwise correlation coefficients (CC) were estimated to assess relationship among markers expression.
Results: PTEN loss was encountered in 5 cases (28%) of plasmacytoid UC. In contrast, high levels of phos-mTOR (mean 218, range 97–285), phos-AKT (mean 211, range 67–295) and phos-S6 (mean 248, range 164–298) were found. Low expression of c-myc (mean 51, range 0–223) and of p27 (mean 61, range 0–225) were noted. phos-AKT expression positively correlated with phos-mTOR (CC = 0.54, P = .02). phos-S6 expression negatively correlated with c-myc expression (CC = -0.67, P < .005).
Conclusions: We found dysregulation of the mTOR pathway in plasmacytoid urothelial carcinoma of the urinary bladder. These results suggest that the use of mTOR inhibitors might be beneficial for patients with this aggressive variant of urothelial carcinoma.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 122, Monday Morning