01.03 Preoperative Serum Levels of miR-210 Associated with Malignant Pheochromocytomas and Paragangliomas

S. Ruff1, R. Ayabe1, P. Malekzadeh1, M. Good1, M. Wach1, N. Nilubol1, E. Kebebew2, D. Patel1  1National Cancer Institute,Thoracic And Oncologic Surgery Branch,Bethesda, MD, USA 2Stanford University,Palo Alto, CA, USA

Introduction: There are no predictive clinical or laboratory tests that accurately distinguish between benign and malignant pheochromocytomas or paragangliomas (PPGLs). There is a link between dysregulated microRNAs and adverse prognosis in multiple malignancies. The overexpression of miR-210 has been found to be associated with the hypoxic state of the tumor microenvironment. The aim was to investigate if serum miR-210 levels could be used as a marker of malignancy in patients with PPGLs. 

Methods:  Patients with PPGLs (n=35) underwent an operation and had preoperative serum collected. Clinical demographics, genetic mutations, primary tumor size, postoperative biochemical response, and the development of recurrence or metastatic disease was prospectively collected. Total microRNA was extracted from the preoperative serum samples and miR-210 levels were measured by quantitative RT-PCR and normalized to miR-16. On univariable analysis primary tumor size, age, gender, race, body mass index, genetic mutation, miR-210 level, primary tumor site, and postoperative biochemical response from initial surgery was examined. Variables with a p-value <0.1 were included in a multivariable analysis.

Results: Of the 35 patients in our study, 10 underwent an operation for metastatic or recurrent disease and 25 did not develop recurrence or metastatic disease after their initial operation (median follow-up time of 65.7 months). Most patients had a primary pheochromocytoma (seven out of ten patients with metastasis/recurrence versus 17 out of 25 patients with benign pheochromocytomas). The most common mutation in the entire cohort was SDHB (n=10). There was a significantly lower serum miR-210 level in patients with metastasis/recurrence (2.3 versus 3.1, p=0.013) and larger primary tumor size in patients with a metastasis/recurrence (6.7 cm versus 4.1 cm, p=0.043) on univariable analysis. Age, gender, race, body mass index, genetic mutation, and postoperative biochemical response were not associated with recurrent or metastatic disease. Multivariable analysis did not show a significant difference for tumor size or miR-210 levels between these two groups.

Conclusion: Serum miR-210 expression levels were lower in patients with metastatic or recurrent disease at time of operation. Mir-210 expression may be a biomarker associated with metastatic or recurrent disease.