Growth Factor Receptor Expression and Microvascular Density in Adrenal and Extra-Adrenal Pheochromocytomas/Paragangliomas (PG)
MB Kraemer, K Idrees, D Wang, S Liles, M Hesling, RD Chernock, JS Lewis, Jr, WE Grizzle, O Hameed. University of Alabama, Birmingham, AL; Washington University, St. Louis, MO
Background: Malignant PGs are rare and usually resistant to traditional chemotherapy. Recently, several reports have been published in which therapeutic responses were achieved with the multi-target tyrosine kinase inhibitor sunitinib. This prompted us to study the expression of different tyrosine kinase growth factor receptors in PGs.
Design: Fifty two benign and 14 malignant (metastatic) adrenal and extra-adrenal PGs were reviewed and punched in triplicate to produce a tissue microarray. Immunohistochemistry for VEGFR1, VEGFR2 and IGFR-β was performed and semiquantitatively evaluated utilizing an "H-score" ranging from 0-400. HER2 expression was also evaluated. Expression was correlated to the clinical and pathological features of the tumors, as well as to their microvascular density (MVD) which was calculated by BioquantR Image Analysis software (R&M Biometrics) following CD31 immunostaining.
Results: No tumor expressed HER2. VEGFR1 expression was seen in 14 (100%) malignant and 50 (96%) benign PGs with strong expression in 13 (93%) malignant vs. 20 (38%) benign cases (p<0.001). VEGFR2 expression was seen in 14 (100%) malignant and 48 (92%) benign PGs with strong expression in 12 (86%) malignant and 22 (42%) benign cases (p=0.01). IGFR expression was seen in 13 (92%) malignant and 44 (85%) benign PGs with strong expression in 10 (71%) malignant cases and 13 (25%) benign cases (p=0.003). The average H-scores of all receptors were significantly higher in malignant than benign PGs (336 vs. 193 for VEGFR1; 331 vs. 184 for VEGFR2; and 279 vs. 139 for IGFR) (all P values = or <0.001). The average MVD was also higher in malignant cases (263.8 vs. 179.2; P=0.08). Correlation between the different parameters is shown in the table.
Conclusions: Tyrosine kinase receptor expression is common in PGs, with more frequent and stronger expression in malignant cases. Moreover, expression correlated with size and weight, and negatively with overall survival. These findings support the rationale for considering tyrosine kinase inhibitors for the treatment of malignant PGs.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 79, Monday Morning