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ASO Author Reflections: PTTG1 Protein Expression in Adrenocortical Carcinoma
Minerva Angélica Romero Arenas, MD, MPH1,2 and Nancy D. Perrier, MD1
1The University of Texas MD Anderson Cancer Center, Houston, TX; 2The University of Texas Rio Grande Valley, Edinburg, TX
PAST
Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis owing to late diagnosis.1 Histologi- cal parameters may not always distinguish benign adrenocortical adenomas (ACAs) from ACCs. Additional techniques like immunohistochemical markers could pro- vide significant clinical utility. Pituitary-tumor transforming gene (PTTG1/securin) encodes securin, a protein that prevents separins from promoting sister chro- matid separation.2,3 PTTG1 has been shown to modulate cancer-related angiogenesis, metastasis, and therapeutic response and is highly expressed across a number of tumor types.3,4 This study was designed to validate the potential role of PTTG1 protein levels in ACC by utilizing a tissue microarray (TMA)-based analysis of PTTG1 nuclear pro- tein levels across normal adrenal tissue, ACA, and ACC.5 Differential PTTG1 expression levels between ACC and ACA were validated using publicly available messenger RNA (mRNA) expression data. Lastly, PTTG1 protein levels in ACC were correlated with clinical features.
ASO Author Reflections is a brief invited commentary on the article, “Protein Expression of PTTGI as a Diagnostic Biomarker in Adrenocortical Carcinoma.” Ann Surg Oncol. 2018;25:801-807.
@ Society of Surgical Oncology 2018 First Received: 1 November 2018
N. D. Perrier, MD e-mail: NPerrier@mdanderson.org
PRESENT
On TMA-1, nuclear protein expression of PTTG1 was detected in 31% of ACC, although it was not detected in any of the ACA or normal adrenals. On TMA-2, nuclear protein expression of PTTG1 was observed in 74% of ACC tumors and detected in one (7%) of the ACA specimens and five (56%) of the normal adrenal gland specimens. The mRNA expression level of PTTG1 was significantly higher in ACC compared with normal adrenals (p < 0.00001), whereas the expression of PTTG1 was comparable between ACA and normal adrenals. On both TMAs, elevated nuclear protein expression of PTTG1 (IHC score of 2 or 3) was significantly associated with higher Ki-67 index (p = 0.0008 and p = 0.0053, respectively) compared with lower PTTG1 IHC scores (0 or 1). PTTG1 nuclear protein expression did not correlate with other clinical parameters, including TP53 protein expression, tumor size, age at diagnosis, Weiss score, overall survival, or metastasis on either of the TMAs.
FUTURE
Nuclear PTTG1 protein expression, assessed by IHC, could be a useful clinical tool to help distinguish ACCs from ACAs and normal adrenal glands. Despite best efforts to match the preparation of both TMAs using the lowest possible antibody concentration at 1 µg/ml for TMA-1 and 5 µg/ml for TMA-2, because the lower concentration did not provide good staining on TMA-2. The potential of using PTTG1 in distinguishing ACCs from ACAs would be better supported if the studies could be repeated with IHC at the same concentration. Our data showed a correlation between increased PTTG1 staining and Ki-67 proliferation index, a known prognostic indicator in ACC. A larger study looking at PTTG1 protein expression and ACC patient survival should be completed. In addition to having
diagnostic potential in adrenal tumors, expression of PTTG1 may have therapeutic and prognostic implications, which should be explored separately.
DISCLOSURE The authors have no conflicts of interest to disclose.
REFERENCES
1. Allolio B, Fassnacht M. Clinical review: adrenocortical carci- noma: clinical update. J Clin Endocr Metab. 2006;91(6):2027-37.
2. Zou H, McGarry TJ, Bernal T, Kirschner MW. Identification of a vertebrate sister-chromatid separation inhibitor involved in trans- formation and tumorigenesis. Science. 1999;285(5426): 418-22.
3. Tfelt-Hansen J, Kanuparthi D, Chattopadhyay N. The emerging role of pituitary tumor transforming gene in tumorigenesis. Clin Med Res. 2006;4(2):130-7.
4. Vlotides G, Eigler T, Melmed S. Pituitary tumor-transforming gene: physiology and implications for tumorigenesis. Endocr Rev. 2007;28(2):165-86.
5. Romero Arenas MA, Whitsett TG, Aronova A, et al. Protein expression of PTTG1 as a diagnostic biomarker in adrenocortical carcinoma. Ann Surg Oncol. 2018;25(3):801-7.