Immunohistochemical Expression of Phosphorylated S6 Is Associated with Degree of Differentiation in Penile Squamous Cell Carcinoma
Alcides Chaux, Antonio L Cubilla, Jessica Hicks, Kristen L Lecksell, Arthur L Burnett, George J Netto. Johns Hopkins University, Baltimore, MD; Instituto de Patologia e Investigacion, Paraguay
Background: Activation of the mTOR pathway is essential for normal cell growth, differentiation, and specialization. Additionally, dysregulation of this pathway has been implicated in the pathogenesis of several cancers, including tumors of the kidney, prostate, and bladder. However, studies on the status of the mTOR pathway in penile squamous cell carcinomas (SCC) are scant. Herein, we evaluate the immunoexpression of members of the mTOR pathway in a large series of penile carcinomas.
Design: One-hundred and twelve cases of penile SCC were used to build 4 tissue microarrays (TMA). Each tumor was sampled 3–12 times. TMA spots were scanned using the APERIO system and uploaded to the TMAJ platform (http://tmaj.pathology.jhmi.edu). Immunohistochemical expression of phosphorylated AKT (phos-AKT), phosphorylated mTOR (phos-mTOR), and phosphorylated S6 (phos-S6) was assessed by immunohistochemistry, using a previously described protocol (Am J Surg Pathol 2011;35:1549). Percentages of positive cells were estimated in each TMA spot and average values per case were used for data analysis.
Results: Low extent of phos-AKT (mean 1.3%, SD 2%) and phos-mTOR (mean 0.5%, SD 2%) expression were observed. Higher phos-S6 expression was noted (mean 38%, SD 26%). No association was observed between expression levels of phos-AKT, phos-mTOR, or phos-S6 and histological subtype (P > .05). However, low grade (grades 1 or 2) tumors had significantly higher levels of phos-S6 than high grade (grade 3) tumors (52% vs. 31%, P = .0001). The difference in phos-S6 expression by histologic grade was independent of histologic subtype. There was no significant association between phos-AKT or phos-mTOR and histologic grade.
Conclusions: Expression levels of phos-S6 were associated with histologic grade in penile SCC, independent of histologic subtype. Well to moderately differentiated tumors had higher levels of phos-S6 compared to high grade tumors. In light of the recently identified specific inhibitors of S6 kinases, these findings might be useful in the planning of future clinical trials for patients with penile cancer.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 148, Monday Afternoon