The relation of pituitary adenomas invasiveness and the proliferative index measured by immunoexpression of topoisomerase IIα
Abstract
Introduction: Cavernous sinus invasion by pituitary adenoma affects surgical procedure radicality and consequently the postoperative course and prognosis in pituitary adenoma treatment. The search for pituitary adenoma aggressive behaviour markers is still a matter of debate.
Material and methods: This study evaluates the relation of pituitary adenoma invasiveness to the expression of topoisomerase IIα in 72 patients who underwent transsphenoidal pituitary surgery. The assessment of tumour growth was conducted according to the Hardy scale as modified by Wilson and the Knosp scale. Topoisomerase IIα expression in tumour specimens was evaluated using immunohistochemical staining.
Results: There was a correlation between the Knosp scale degree and the topoisomerase IIα expression (Spearman R = 0.3611, p < 0.005). The Kruskal-Wallis H test (p = 0.0034) showed that there was a statistically significant topoisomerase IIα expression increase in tumours classified as grade E on the Hardy scale. The topoisomerase IIα expression correlated also with tumour size (Spearman R = 0.4117, p < 0.001). Higher levels of expression were observed in macroadenomas, as compared to microadenomas (p < 0.05, Mann-Whitney test). Topoisomerase IIα expression correlated with cavernous sinus invasion.
Conclusions: The topoisomerase IIα expression correlated more with invasiveness than with extensiveness, which might make it an eminently useful marker in the assessment of aggressive pituitary adenoma behaviour.
Keywords: pituitary adenomaKnosp scaletopoisomerase IIα expressioncavernous sinuses invasion
References
- Faglia G. Epidemiology and pathogenesis of pituitary adenomas. Acta Endocrinol. 1993; 129(Suppl 1): 1–5.
- Kontogeorgos G. Classification and pathology of pituitary tumors. Endocrine. 2005; 28(1): 27–35.
- Korali Z, Müller A, Schopol J. Hypophysentumoren und Kraniopharyngeome. Manual — Hirntumoren und primäre Tumoren des Rückenmarks. Tumorzentrum, München 2001: 89–108.
- Elster AD. Imaging of the sella: anatomy and pathology. Semin Ultrasound CT MR. 1993; 14(3): 182–194.
- Greenberg M. Handbook of neurosurgery. Thieme, New York 2001.
- Rennert J, Doerfler A. Imaging of sellar and parasellar lesions. Clin Neurol Neurosurg. 2007; 109(2): 111–124.
- Wilson C. Neurosurgical management of large and invasive pituitary tumours. In: Tindal G, Collins W. ed. Clinical management of pituitary disorders. Raven Press, New York 1979: 335–342.
- Knosp E, Steiner E, Kitz K, et al. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery. 1993; 33(4): 610–617; discussion 617.
- Ahmadi J, North CM, Segall HD, et al. Cavernous sinus invasion by pituitary adenomas. AJR Am J Roentgenol. 1986; 146(2): 257–262.
- Fahlbusch R, Buchfelder M. Transsphenoidal surgery of parasellar pituitary adenomas. Acta Neurochir (Wien). 1988; 92(1-4): 93–99.
- Chacko G, Chacko AG, Lombardero M, et al. Clinicopathologic correlates of giant pituitary adenomas. J Clin Neurosci. 2009; 16(5): 660–665.
- Sol YuLi, Lee SK, Choi HS, et al. Evaluation of MRI criteria for cavernous sinus invasion in pituitary macroadenoma. J Neuroimaging. 2014; 24(5): 498–503.
- Horvath E, Lloyd RV, Kovacs K. Plurihormonal adenoma. In: Delellis RA, Lloyd RV, Heitz PU, Eng C. ed. World Health Organisation Classification of Tumours: Pathology & Genetics — Tumours of Endocrine Organs. IARC Press, Lyon 2004: 35.
- Kontogeorgos G, Watson Jr, Lindell EP. Growth hormone producing adenoma. In: Delellis RA, Lloyd RV, Heitz PU, Eng C. ed. World Health Organisation Classification of Tumours: Pathology & Genetics — Tumours of Endocrine Organs. IARC Press, Lyon 2004: 14–19.
- Lloyd RV, Kovacs K, Young Jr WF. Pituitary tumours: introduction. In: Delellis RA, Lloyd RV, Heitz PU, Eng C. ed. World Health Organisation Classification of Tumours: Pathology & Genetics — Tumours of Endocrine Organs. IARC Press, Lyon 2004: 10–13.
- Kaltsas GA, Nomikos P, Kontogeorgos G, et al. Clinical review: Diagnosis and management of pituitary carcinomas. J Clin Endocrinol Metab. 2005; 90(5): 3089–3099.
- Heaney A. Management of aggressive pituitary adenomas and pituitary carcinomas. J Neurooncol. 2014; 117(3): 459–468.
- Paek KI, Kim SH, Song SH, et al. Clinical significance of Ki-67 labeling index in pituitary macroadenoma. J Korean Med Sci. 2005; 20(3): 489–494.
- Fahlbusch R, Buslei R. The WHO classification of pituitary tumours: a combined neurosurgical and neuropathological view. Acta Neuropathol. 2006; 111(1): 86–87.
- Grossman AB. The 2004 World Health Organization classification of pituitary tumors: is it clinically helpful? Acta Neuropathol. 2006; 111(1): 76–77.
- Saeger W, Lüdecke DK, Buchfelder M, et al. Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol. 2007; 156(2): 203–216.
- Turner HE, Wass JA. Are markers of proliferation valuable in the histological assessment of pituitary tumours? Pituitary. 1999; 1(3-4): 147–151.
- Kontogeorgos G. Predictive markers of pituitary adenoma behavior. Neuroendocrinology. 2006; 83(3-4): 179–188.
- Bildrici K, Tel N, Ozalp SS, et al. Prognostic significance of DNA topoisomerase II-alpha (Ki-S1) immunoexpression in endometrial carcinoma. Eur J Gynaecol Oncol. 2002; 23(6): 540–544.
- Boege F, Gieseler F, Biersack H, et al. The measurement of nuclear topoisomerase II inhibition in vitro: a possible tool for detecting resistance on a subcellular level in haematopoietic malignancies. Eur J Clin Chem Clin Biochem. 1992; 30(2): 63–68.
- Koshiyama M, Fujii H, Kinezaki M, et al. Immunohistochemical expression of topoisomerase IIalpha (Topo IIalpha) and multidrug resistance-associated protein (MRP), plus chemosensitivity testing, as chemotherapeutic indices of ovarian and endometrial carcinomas. Anticancer Res. 2001; 21(4B): 2925–2932.
- Depowski PL, Rosenthal SI, Brien TP, et al. Topoisomerase IIalpha expression in breast cancer: correlation with outcome variables. Mod Pathol. 2000; 13(5): 542–547.
- Feng Y, Zhang H, Gao W, et al. Expression of DNA topoisomerase II-α: Clinical significance in laryngeal carcinoma. Oncol Lett. 2014; 8(4): 1575–1580.
- Kiyoshi M. Immunocytochemical study of 150 tumours with clinicopathologic correlation. Cancer. 1983; 52: 648–653.
- Vidal S, Kovacs K, Horvath E, et al. Topoisomerase IIalpha expression in pituitary adenomas and carcinomas: relationship to tumor behavior. Mod Pathol. 2002; 15(11): 1205–1212.
- Di Chiro G, Nelson KB. The volume of the sella turcica. Am J Roentgenol Radium Ther Nucl Med. 1962; 87: 989–1008.
- Goel A, Nadkarni T, Muzumdar D, et al. Giant pituitary tumors: a study based on surgical treatment of 118 cases. Surg Neurol. 2004; 61(5): 436–45; discussion 445.
- Cottier JP, Destrieux C, Brunereau L, et al. Cavernous sinus invasion by pituitary adenoma: MR imaging. Radiology. 2000; 215(2): 463–469.
- Sarkar S, Chacko AG, Chacko G. Clinicopathological correlates of extrasellar growth patterns in pituitary adenomas. J Clin Neurosci. 2015; 22(7): 1173–1177.
- Landolt AM, Shibata T, Kleihues P. Growth rate of human pituitary adenomas. J Neurosurg. 1987; 67(6): 803–806.
- Yilmaz M, Vural E, Koc K, et al. Cavernous sinus invasion and effect of immunohistochemical features on remission in growth hormone secreting pituitary adenomas. Turk Neurosurg. 2015; 25(3): 380–388.
- Moldovan IM, Melincovici C, Mihu C, et al. Diagnostic criteria in invasive pituitary adenomas. Rom Neurosurg. 2016; 30(3): 345–359.
- Wolfsberger S, Wunderer J, Zachenhofer I, et al. Expression of cell proliferation markers in pituitary adenomas--correlation and clinical relevance of MIB-1 and anti-topoisomerase-IIalpha. Acta Neurochir (Wien). 2004; 146(8): 831–839.
- Trofimiuk-Müldner M, Bałdys-Waligórska A, Sokołowski G, et al. Topoisomerase IIα as a prognostic factor in pituitary tumors. Pol Arch Med Wewn. 2014; 124(10): 500–508.
