67th Annual Meeting Abstracts

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mTOR/p70S6 Pathway In Clear Cell Renal Cell Carcinoma (cc-RCC): Comparison Of Activation In Primary Tumor And Matched Metastatic Deposits
Alexander Kutikov¹, Brian L. Egleston¹, Tasha Morrison², *Elizabeth P. Henske², *Min Huang¹, *Tahseen Al-Saleem¹, Robert G. Uzzo^1
1Fox Chase Cancer Center, Philadelphia, PA;²Brigham And Women's Hospital, Boston, MA

Introduction: The mTOR/p70S6 kinase pathway regulates cell growth, proliferation, motility, and survival. Here we assess and compare its activation in primary cc-RCC and matched metastases (n=34).
Methods: Tissues from primary renal tumors and matched resected/biopsied metastatic deposits were obtained from our institutional biosample repository. Tissue microarray (TMA) slides were constructed to include normal kidney controls. TMAs were incubated with rabbit polyclonal antibodies against Ser2448 of p-mTOR and Ser235/236 of p-ribosomal protein S6. Semiquantitative assessments of immunohistochemical staining were made, and Spearman rank correlation coefficients were used to assess associations between variables.
Results: Both primary tumors and matched metastases exhibited heterogeneous levels of staining for p-mTOR and for p-S6. We observed a strong relationship between phosphorylation of S6 in primary tumors and their matched metastases (p<0.0001, Figure 1); however in clear cell tumors we did not identify statistically significant relationships between staining for p-mTOR in the primary tumors and their matched metastases (p=0.179). No statistically significant association was seen between level of p-mTOR expression and p-S6 in primary cc-RCC (p=0.470), nor within metastatic lesions (p=0.368).
Conclusions: Our data suggest that mTOR/p70S6 kinase pathway activation is common, but not ubiquitous in patients with metastatic cc-RCC. We document a strong relationship between phosphorylation of S6 in primary clear cell tumors and their matched metastases. These findings are novel and deserve further study.

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