Investigation of IMPDH2 overexpression in renal cell carcinoma (RCC) & its association with oncologic outcomes
| Autor: | Koichi Okumura, Ramya Krishna Velagapudi, Xiang Ao, Zheng Zhu, Jaskirat Randhawa, Atsuo T. Sasaki, Satoshi Kofuji, Hirofumi Yoshino, Alejandro Marinos Velarde, Kara Finley, Rand Naffouje, Roman Jandarov, Matthew Koch, Arun Sendilnathan, Kelsey Dillehay McKillip |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 37:594-594 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 594 Background: Approximately 40% of locoregional RCC patients relapse after nephrectomy leading to lower 5 year survival rates of 53% (stage III) & 8% (metastatic). No biomarkers of prognostic significance are in clinical use at this time. It is important to identify biomarkers that can better inform clinicians the nature of disease & personalize treatment. It is even better if the biomarkers are targetable with drugs. Inosine 5”-mono-phosphate dehydrogenase type II (IMPDH2), a rate limiting enzyme in the de novo guanine nucleotide biosynthesis is upregulated in many tumor types. Work by Sasaki laboratory showed increased GTP synthesis by IMPDH2 upregulation is important for cell growth, metastasis & cell maintenance in Gliobastoma Multiforme cell lines. Hypothesis: We are investigating the feasibility of using IMPDH2 expression in RCC as a diagnostic & prognostic biomarker. Methods: 45 cases of clear cell RCC (all stages) were identified by chart review. Slides reviewed to identify blocks with carcinoma, normal tissue & interface. Tissue microarray (TMA) was constructed using the fully automated TMA Master. TMA sectioned and stained with H &E & IMPDH2 antibody. Staining interpretation: TMA stained with IMPDH2 were reviewed based on IRS scoring system (PP x SI) - percentage positive(PP) cells (Negative-0, ≤ 10% -1, ≥ 11%- ≤ 50%- 2, ≥ 51%-≤ 80% -3, and ≥ 81%-4) & staining intensity (SI) (Negative-0, Weak-1, Moderate-2, and Strong-3). The scoring pathologist was blinded to the clinical data & outcomes of patients. Results: Preliminary results show IMPDH2 is overexpressed in RCC and tumor-normal interface compared to normal kidney. Further analyses are ongoing if IMPDH2 overexpression correlates with pertinent clinical & pathological variables including TNM stage, histologic grade (Fuhrman Grade) & oncologic outcomes including overall survival (OS) & risk of relapse. Conclusions: In the era of Sunitinib being approved as an adjuvant therapy (but not widely used due to lack of OS data), the above data will be important to verify if IMPDH2 can be used as a clinically useful test & may give insight to future personalized & targeted treatment strategies (IMPDH2 inhibitors like mycophenolate) for RCC. |
| Databáze: | OpenAIRE |
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