Articles

Expression of the Pituitary Tumor Transforming Gene (PTTG1) in Pheochromocytoma as a Potential Marker for Distinguishing Benign Versus Malignant Tumors

Abstract

The Distinction between malignant and benign pheochromocytoma has always been a diagnostic challenge over the last decades. To date, the only reliable criterion is metastasis. The aim of the present study was to investigate the possible expression of pituitary-tumor transforming gene (PTTG1) and retinoblastoma (Rb) in benign and malignant pheochromocytoma. Paraffin blocks of 44 and 11 patients diagnosed with benign and malignant pheochromocytoma were collected. Parameters such as sex, age, tumor size, necrosis, and histological features were compared between the benign and malignant groups as well as immunohistochemical labeling using specific antibodies. PTTG1 showed negative expression in all (44) benign and 9 out of 11 (81.8%) malignant tumors with only 2 out of 11 (18.2%) malignant tumors showed positive reactivity for PTTG1 (P: 0.037) with spindle cell histological pattern in both of them (P: 0.013). Although Rb expression in malignant tumors (81.8%) was slightly more than the benign ones (52.3%), no statistically significant correlation was observed (P: 0.087). These results suggest that PTTG1 immunostaining may play a key role in distinguishing between benign and malignant phaeochromocytoma. However, larger studies are necessary to confirm the outcomes of the present study.

M Thompson LD. Pheochromocytoma of the Adrenal gland Scaled Score (PASS) to separate benign from malignant neoplasms: a clinicopathologic and immunophenotypic study of 100 cases. Am J Surg Pathol 2002;26(5):551-66.

Rao F, Keiser HR, O’Connor DT. Malignant pheochromocytoma: chromaffin granule transmitters and response to treatment. Hypertension 2000;36(6):1045-52.

John H, Ziegler WH, Hauri D, et al. Pheochromocytomas: can malignant potential be predicted? Urology 1999;53(4):679-83.

Clarke MR, Weyant RJ, Watson CG, et al. Prognostic markers in pheochromocytoma. Hum Pathol 1998;29(5):522-6.

Van der Harst E, Bruining HA, Jaap Bonjer H, et al. Proliferative index in phaeochromocytomas: does it predict mthe occurrence of metastases? J Pathol 2000;191(2):175-80.

Brown HM, Komorowski RA, Wilson SD, et al. Predicting metastasis of pheochromocytomas using DNA flow cytometry and immunohistochemical markers of cell proliferation. Cancer 1999;86(8):1583-9.

Zhang X, Horwitz GA, Heaney AP, et al. Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. J Clin Endocrinol Metab 1999;84(2):761-7.

Pei L, Melmed S. Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Mol Endocrinol1997;11(4):433-41.

Zhang X, Horwitz GA, Prezant TR, et al. Structure, expression, and function of human pituitary tumortransforming gene (PTTG). Mol Endocrinol 1999;13(1):156-66.

Zou H, McGarry TJ, Bernal T,et al. Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 1999;285(5426):418-22.

Pei L. Identification of c-myc as a down-stream target for pituitary tumor-transforming gene. J Biol Chem 2001;276(11):8484-91.

Pei L. Activation of mitogen-activated protein kinase cascade regulates pituitary tumor-transforming gene transactivation function. J Biol Chem 2000;275(40):31191-8.

Yu R, Lu W, Chen J, et al. Overexpressed pituitary tumortransforming gene causes aneuploidy in live human cells. Endocrinology 2003;144(11):4991-8.

Weinberg RA. The retinoblastoma protein and cell cycle control. Cell 1995;81(3):323-30.

Bookstein R, Rio P, Madreperla SA, et al. Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma. Proc Natl Acad Sci U S A 1990;87(19):7762-6.

Lee E, To H, Shew JY, et al. Inactivation of the retinoblastoma susceptibility gene in human breast cancers. Science 1988;241(4862):218-21.

Horowitz JM, Yandell DW, Park SH, et al. Point mutational inactivation of the retinoblastoma antioncogene. Science 1989;243(4893):937-40.

Sherr CJ. Cancer cell cycles. Science 1996;274(5293):1672-7.

Saffar H, Sanii S, Heshmat R, et al. Expression of galectin- 3, nm-23, and cyclooxygenase-2 could potentially discriminate between benign and malignant pheochromocytoma. Am J Clin Pathol 2011;135(3):454-60.

Mornex R, Berthezene F, Peyrin L, et al. Phaeochromocytomes malins. Arch Mal Coeur Vaiss 1979;72(Spec no): 96-102.

Ilona Linnoila R, Keiser HR, Steinberg SM, et al. Histopathology of benign versus malignant sympathoadrenal paragangliomas: clinicopathologic study of 120 cases including unusual histologic features. Hum Pathol 1990;21(11):1168-80.

Norton JA LB, Jensen RT. The adrenal gland. In : DeVita VT, Hellman S, Rosenberg SA, editors. Cancer: principles and practice of oncology. 4th ed. Philadelphia: J. B. Lippincott; 1993: p. 1365-71.

Carlsen E, Abdullah Z, Kazmi S, et al. Pheochromocytomas, PASS, and immunohistochemistry. Horm Metab Res 2009;41(9):715-9.

Plouin PF, Chatellier G, Fofol I, et al. Tumor recurrence and hypertension persistence after successful pheochromocytoma operation. Hypertension 1997;29(5):1133-9.

Hosoda S, Suzuki H, Oguri T,et al. Adrenal pheochromocytoma with both benign and malignant components. Pathol Int 1976;26(4):519-31.

King ESJ. Malignant phæochromocytoma of the adrenals. J Pathol Bacteriol 1931;34(4):447-52.

Heaney AP, Singson R, McCabe CJ,et al. Expression of pituitary-tumour transforming gene in colorectal tumours. Lancet 2000;355(9205):716-9.

Pei L. Pituitary tumor-transforming gene protein associates with ribosomal protein S10 and a novel human homologue of DnaJ in testicular cells. J Bioll Chem 1999;274(5):3151-8.

Solbach C, Roller M, Fellbaum C, et al. PTTG mRNA expression in primary breast cancer: a prognostic marker for lymph node invasion and tumor recurrence. Breast 2004;13(1):80-1.

Sáez C, Pereda T, Borrero JJ, et al. Expression of hpttg proto-oncogene in lymphoid neoplasias. Oncogene 2002;21(53):8173-7.

Shibata Y, Haruki N, Kuwabara Y, et al. Expression of PTTG (pituitary tumor transforming gene) in esophageal cancer. Jpn J Clin Oncol 2002;32(7):233-7.

Gupta D, Shidham V, Holden J, et al. Prognostic value of immunohistochemical expression of topoisomerase alpha II, MIB-1, p53, E-cadherin, retinoblastoma gene protein product, and HER-2/neu in adrenal and extra-adrenal pheochromocytomas. Appl Immunohistochem Mol Morphol 2000;8(4):267-74.

Lam K, Lo C, Wat N,et al. The clinicopathological features and importance of p53, Rb, and mdm2 expression in phaeochromocytomas and paragangliomas. J Clin Pathol 2001;54(6):443-8.

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IssueVol 53, No 4 (2015) QRcode
SectionArticles
Keywords
Pheochromocytoma Immunohistochemistry PTTG1 RB

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How to Cite
1.
Haji Amousha MR, Sabetkish N, Sabet Kish N, Heshmat R, Rajabiani A, Saffar H, Haghpanah V, Tavangar SM. Expression of the Pituitary Tumor Transforming Gene (PTTG1) in Pheochromocytoma as a Potential Marker for Distinguishing Benign Versus Malignant Tumors. Acta Med Iran. 1;53(4):236-241.