Ki67 in endocrine neoplasms: to count or not to count, this is the question! A systematic review from the English langua
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REVIEW
Ki67 in endocrine neoplasms: to count or not to count, this is the question! A systematic review from the English language literature E. Guadagno1 · E. D’Avella2 · P. Cappabianca2 · A. Colao3 · M. Del Basso De Caro1 Received: 4 March 2020 / Accepted: 23 April 2020 © Italian Society of Endocrinology (SIE) 2020
Abstract Background Endocrine neoplasms are generally slow-growing tumors that can show hormonal activity and give metastases. In most cases they are benign and clearly malignant forms are easy to diagnose. However, borderline forms may occur and be, for the pathologists, very difficult to classify. In these cases, there is a strong need to identify factors that may aid. Official classification systems for endocrine neoplasms are based on the evaluation of proliferation and, in most cases, they rely on mitotic count. In support, the study of Ki67 is carried out which, however, has not yet been included in any official classification system, except for neuroendocrine neoplasms of the gastro-entero-pancreatic tract. Purpose The aim of the present study was to investigate the proven or unproven role of Ki67 in endocrine neoplasms, in different districts, in order to bring to light the substantial differences, in terms of proliferation, existing between neoplasms so similar, but at the same time, so different. Methods A thorough search of English language literature was performed, looking for articles concerning Ki67 in five endocrine neoplasms (pituitary adenomas, thyroid neoplasms, adrenocortical neoplasms, pheochromocytomas and paragangliomas). Results From 2170, 236 articles were selected and it was seen that the endocrine neoplasm in which Ki67 was most studied was the pituitary, where it still shows a controversial role. In other neoplasms different roles were identified. Conclusion The pathologist should be aware of the contribution that this proliferative marker can give to the diagnosis and, sometimes, to the therapy selection, for the clinician. Keywords Ki67 · Ki-67 · Endocrine · Proliferation · Prognosis
Background Ki67: definition
* E. Guadagno [email protected] 1
Pathology Section, Department of Advanced Biomedical Sciences, “Federico II” University of Naples, Via Pansini 5, 80131 Naples, Italy
2
Division of Neurosurgery, Department of Neurosciences, Reproductive and Odontostomatological Sciences, “Federico II” University of Naples, Via Pansini 5, 80131 Naples, Italy
3
Endocrinology Section, Department of Clinic Medicine and Surgery, “Federico II” University of Naples, Via Pansini 5, 80131 Naples, Italy
The study of cell kinetics in human tumors has contributed to the understanding of growth characteristics and to the definition of effective treatment methods for malignant tumors [1]. Ki67 is a nuclear protein exclusively present in cycling cells, but not in resting cells (G0) and whose function has been unknown for years. Recently, it was shown that it plays an essential role in the control and timing of cell proliferation, by covering the surface of chromosome
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