Abstract
The principal factors involved in pituitary adenoma formation are unknown. DNA-flow cytometry is a useful study providing an estimation of a tumor proliferative rate. In this study, DNA-flow cytometry was performed to evaluate its capability to both assess prognosis and predict recurrence. Two hundred and seven fresh pituitary adenoma specimens were assessed by flow cytometry. Pre-operative endocrine function, previous medical treatment, radiographic appearance, surgical findings and immunohistochemistry were recorded for each patient. Patient outcomes were assessed at a mean follow-up of 5.3±3.1 yr. Endocrinologically inactive pituitary adenomas were predominantly euploids (50.8%). The highest proliferation rates occurred in Nelson’s syndrome and the lowest in Cushing’s disease. A significant difference in proliferation was observed with prolactinomas and acromegaly when a medical treatment was performed before primary surgery. Massive histological invasiveness was directly associated with a significant increase in proliferation rate. Radiotherapy did not affect the recurrence rate (4.4%) statistically. In conclusion, DNA-flow cytometry was found to be useful for determining ploidy and obtaining an overview of cell cycle status. It was helpful in identifying patients requiring closer follow-up, such as those with invasive adenomas and Nelson’s syndrome. No single parameter revealed by DNA-flow cytometry could predict tumor prognosis or recurrence in the follow-up of 7.5±1.3 yr.
Similar content being viewed by others
References
Buchfelder M. OP und Strahlentherapie bei Hypophysenadenomen. MMW Fortschr Med 2001, 143: 40–2.
Buchfelder M, Fahlbusch R, Adams EF, Kiesewetter F, Thierauf P. Proliferation parameters for pituitary adenomas. Acta Neurochir 1996, 65 (Suppl): 18–21.
Garcia R, Bueno A, Castañon S, et al. Study ofthe DNA content by flow cytometry and proliferation in 281 brain tumors. Oncology 1997, 54: 112–7.
Lahiri M, Sehgal S, Kak VK, Banerjee AK. Flowcytometric and histopathological correlation of primary intracranial neoplasms. Neurol India 2001, 49: 124–7.
Meij BP, Lopes MBS, Ellegala DB, Alden TD, Laws ER. The long-term significance of microscopic dural invasion in 354 patients with pituitary adenomas treated with transsphenoidal surgery. J Neurosurg 2002, 96: 195–208.
Scheithauer BW, Kovacs KT, Laws ER, Randall RV. Pathology of invasive pituitary tumors with special reference to functional classification. J Neurosurg 1986, 65: 733–44.
Selman WR, Laws ER, Scheithauer BW, Carpenter SM. The ocurrence of dural invasion in pituitary adenomas. J Neurosurg 1986, 64: 402–7.
Fahlbusch R, Schrell U, Buchfelder M. Neurochirurgische Behandlung von Adenomen der Hypophyse. Nervenheilkunde 1985, 62: 1556–60.
Losa M, Franzin A, Mortini P, Terreni MR, Mangili F, Giovanelli M. Usefulness of markers of cell proliferation in the management of pituitary adenomas. Clin Sci (Lond) 1998, 95: 129–35.
Boeck G. Current status of flow cytometry in cell and molecular biology. Int Rev Cytol 2001, 204: 239–98.
Jaroszeski MJ, Radcliff G. Fundamentals of flow cytometry. Mol Biotechnol 1999, 11: 37–53.
Magennis DP. Nuclear DNA in histological and cytological speciments: measurement and prognostic significance. Br J Biomed Sci 1997, 54: 140–8.
O’Gorman MRG. Clinical relevantfunctional flow cytometry assays. Clin Lab Med 2001, 21: 779–94.
Wedemeyer N, Potter T. Flow cytometry: an ‘old’ tool for novel applications in medical genetics. Clin Genet 2001, 60: 1–8.
Givan AL. Principles of flow cytometry: an overview. Methods Cell Biol 2001, 63: 19–50.
Nunez R. Introduction to the field of cytometry and its importance in Biomedicine. Curr Issues Mol Biol 2001, 3: 37–8.
Villas BH. Flow cytometry: an overview. Cell Vis 1998, 5: 56–61.
Ormerod MG, Tribukait B, Garretti W. Consensus report of the task force on standartisation of DNA flow cytometry in clinical pathology. Anal Cell Pathol 1998, 17: 103–10.
Bononi PL, McCoy JJr., Martinez AJ, Janosky JE, Amico JA. Flow cytometric analysis of growth hormone-secreting pituitary adenomas.Horm Res 1994, 42: 262–6.
Fitzgibbons PL, Appley AJ, Turner RR, et al. Flow cytometric analysis of pituitary tumors. Cancer 1988, 62: 1556–60.
Kiesewetter F, Haneke E, Lennert K, Hornstein PO, Fartasch M. Cutaneous lymphoepiteloid lymphoma (Lennert’s lymphoma). Am J Dermatopathol 1989, 116: 549–54.
Kiesewetter F, Hornstein OP, Hermanek P, Herrlinger A, Eberhard S. Möglichkeiten der DNS-Impulszytophotometrie bei Nierenkarzinomen. Urologe 1987, 26: 162–7.
Hardy J. Transsphenoidal microsurgery of the normal and pathological pituitary. Clin Neurosurg 1979, 16: 185–217.
Symon L, Jakubowski J, Kendall B. Surgical treatment of giant pituitary adenomas. J Neurol Neurosurg Psychiatry 1979, 42: 973–82.
Baisch H, Göde W, Linden WA. Analysis of PCP-data to determine the fractions of cells in the various phases of the cell cycle. Radiat Environ Biophys 1979, 12: 31–9.
Hsu SM, Raine L, Fange H. A comparative study of the peroxidaseantiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol 1981, 5: 734–8
Anniko M, Holm LE, Tribukait B, Werner S, Wersäll J. The clinical implications of DNA characteristics in human pituitary disease. Acta Otolaryngol 1981, 379(Suppl): 21–8.
Anniko M, Tribukait B, Wersäll J. DNA ploidy and cell phase in human pituitary tumors. Cancer 1984, 53: 1708–13.
Anniko M, Wersäll J. DNA studies for prediction of prognosis of pituitary adenomas? Adv Biosci 1988, 69: 45–51.
Castillo JL, Kawaguchi F, Madariaga J, et al. Factors that affect DNA content analysis by flow cytometry. Rev Med Chil 1999, 127: 1385–97.
Lloyd HM, Jacobi JM, Willgoss DA. DNA synthesis by pituitary tumours, with reference to plasma hormone levels and to effects of bromocriptine. Clin Endocrinol (Oxf) 1995, 43: 79–85.
Lüdecke DK, Beck-Bornholdt HP, Saeger W, Schmidt W. Tumour ploidy in DNA histograms of pituitary adenomas. Acta Neurochir (Wier) 1985, 76: 18–22.
Nagashima T, Murovic JA, Hoshino T, Wilson CB, DeArmond SJ. The proliferative potential of human pituitary tumors in situ. J Neurosurg 1986, 64: 588–93.
Lei T, Bai X, Liu K, Hu W, Xue D, Jiang X. Hormone secretion by cell culture GH-PRL secreting pituitary adenomas: effects of bromocriptine. J Tongji Med Univ 1998, 18: 161–3.
Amar AP, Hinton DR, Krieger MD, Weiss MH. Invasive pituitary adenomas: significance of proliferation parameters. Pituitary 1999, 2: 117–22.
Mastronardi L, Guiducci A, Buttaro FM, Cristallini EG, Puzzilli F, Maira. Relationship among DNA index, S-phaseand invasive behaviour in anterior pituitary adenomas. A cytometric study of 61 cases with Feulgen-positive DNA-analysis. Surg Neurol 2001, 56: 27–32.
Krämer A, Saeger W, Tallen G, Lüdecke DK. DNA measurement, proliferation markers and other factors in pituitary adenomas. Endocr Pathol 1994, 5: 198–211.
Visakorpi T. Proliferative activity determined by DNA flow cytometry and proliferationg cell nuclear antigen (PCNA) immunohistochemistry as a prognostic factor in prostatic carcinoma. J Pathol 1992,168: 7–13.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Machado, A.L.O., Nomikos, P., Kiesewetter, F. et al. DNA-flow cytometry of 207 pituitary adenomas: Ploidy, proliferation, and prognosis. J Endocrinol Invest 28, 795–801 (2005). https://doi.org/10.1007/BF03347568
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03347568