MicroRNA involvement in a metastatic non-functioning pituitary carcinoma.

Abstract

Pituitary carcinomas are extremely rare neoplasms, and molecular events leading to malignant pituitary transformation are largely unknown. Enhanced understanding of molecular mechanisms driving malignant pituitary progression would be beneficial for pituitary carcinoma diagnosis and treatment. Differential microRNA expression in paired primary and metastatic pituitary carcinoma specimens were detected using high-throughput human microRNA microarrays and TaqMan microRNA arrays. Three of significantly deregulated miRNAs were further confirmed using quantitative real-time PCR in the metastatic carcinoma, six atypical pituitary adenomas and eight typical pituitary adenomas. Target genes of microRNAs were bioinformatically predicated and verified in vitro by Western blotting and real-time PCR and in vivo by immunohistochemistry respectively. We present a case of a 50-year-old woman harboring non-functioning pituitary carcinoma with multiple intracranial metastases, and identified up-regulation of miR-20a, miR-106b and miR-17-5p in the metastatic carcinoma as compared to the primary neoplasm. Furthermore, miR-20a and miR-17-5p were increased in the metastatic carcinoma and six atypical pituitary adenomas as compared to eight typical pituitary adenomas as measured by quantitative real-time PCR. Both PTEN and TIMP2 were bioinformatically predicated and confirmed in vitro as target genes of these three microRNAs. As semi-quantified by immunohistochemistry, PTEN was absent and TIMP2 was decreased in the metastatic pituitary carcinoma as compared to pituitary adenomas. Our results suggest microRNA involvement in malignant pituitary progression, whereby increased miR-20a, miR-106b and miR-17-5p promote metastasis by attenuating PTEN and TIMP2 in pituitary carcinoma.