Increased Expression of Ribonucleotide Reductase Subunit M2 in Adrenal Cortical Carcinoma: Possible Mechanism of Chemoresistance
J Lin, DG Thomas, TJ Giordano. University of Michigan, Ann Arbor, MI
Background: Ribonucleotide reductase small subunit M2 (RRM2) plays an essential role in DNA synthesis and repair. Increased expression levels of RRM2 have increasingly been associated with tumor progression, resistance to chemotherapy, and enhanced potential of invasion and metastasis for a wide variety of solid tumor types. In a previously published transcriptional profiling study, we showed that RRM2 transcripts were more abundant in adrenal cortical carcinomas (ACC) compared to adenoma and normal cortex. Given the chemoresistance commonly seen in patients with ACC, we further explored the expression of RRM2 protein in a large cohort of benign and malignant adrenocortical tumors as well as normal cortex and cortical hyperplasia.
Design: RRM2 protein was examined using an adrenocortical-specific tissue array with 138 tissues and immunohistochemistry using an anti-RRM2 antibody. Stained tissue arrays were scored using as 0, 1+, 2+, and 3+ based on the intensity and distrubution of immunoreactivity. Chi-square statistics were used to assess the significance of the results.
Results: The RRM2 IHC results are shown in the chart below, which represents the number of cases of normal cortex (NC), cortical hyperplasia (CH), adrenocortical adenoma (ACA), and adrenocortical carcinoma (ACC) according to their staining results. The ACC cohort clearly shows higher levels of RRM2 immunoreactivity compared to the other tissues (p=8.84 E-10).
Conclusions: Our results validate increased expression of RRM2 protein in a statistically-significant subset of adrenocortical carcinomas, compared to adrenocortical adenoma and other cortical tissues. These results provide a possible explanation why some ACCs exhibit resistance to cytotoxic chemotherapy. Routine immunohistochemical assessment of individual ACC cases for RRM2 protein expression may become clinically usefel and play a role in the selection of the most appropriate therapy for patients with ACC.
Monday, March 22, 2010 9:00 AM
Platform Session: Section H 1, Monday Morning