Protein Expression of PTTG1 as a Diagnostic Biomarker in Adrenocortical Carcinoma
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Adrenocortical carcinoma (ACC) has a poor prognosis and there is an unmet clinical need for biomarkers to improve both diagnostic and prognostic assessment. Pituitary-tumor transforming gene (PTTG1) has been shown to modulate cancer invasiveness and response to therapy. The potential role of PTTG1 protein levels in ACC has not been previously addressed. We assessed whether increased nuclear protein expression of PTTG1 distinguished ACCs from adrenocortical adenomas (ACAs).
Patients with ACC or ACA were identified from prospective tissue banks at two independent institutions. Two tissue microarrays (TMAs) consisting of adrenal specimens from 131 patients were constructed and clinically annotated. Immunohistochemical analysis for PTTG1 and Ki-67 was performed on each TMA.
TMA-1 (n = 80) contained 20 normal adrenals, 20 ACAs, and 40 ACCs, and the validation, TMA-2 (n = 51), consisted of 10 normal adrenals, 14 ACAs, and 27 ACCs. On TMA-1, nuclear staining of PTTG1 was detected in 12 (31%) ACC specimens, while all ACAs and normal adrenal glands were negative for PTTG1. On TMA-2, 20 (74%) of the ACC tumors demonstrated PTTG1 nuclear staining of PTTG1, and 13 (93%) ACA and 4 (44%) normal adrenal glands were negative for PTTG1. ACC tumors with increased PTTG1 protein staining had a significantly higher Ki-67 index (p < 0.001) than those with lower levels of PTTG1.
Increased nuclear protein expression of PTTG1 was observed in malignant adrenal tumors. PTTG1 correlated with Ki-67 in two independent TMAs. PTTG1 is a promising biologic marker in the evaluation of adrenal tumors.
The authors would like to acknowledge Ms. Denái R. Milton for her review of the statistical analyses. Support for Minerva A. Romero Arenas was provided in part by the Golfers Against Cancer and the Dupre Research Fellowship in Surgical Endocrinology. The authors would like to acknowledge support provided by the ATAC Research Fund and the Kristen’s Legacy Fund.
Michael J. Demeure is a paid consultant and has received research support from Arbutus Biopharma Corporation. Minerva Angélica Romero Arenas, Timothy G.Whitsett, Anna Aronova, Samuel A. Henderson, Janine LoBello, Mouhammed Amir Habra, Elizabeth G. Grubbs, Jeffrey E. Lee, Kanishka Sircar, Rasa Zarnegar, Theresa Scognamiglio, Thomas J. Fahey, and Nancy D. Perrier have no conflicts of interest to disclose.