Cyclin A in nonfunctioning pituitary adenomas
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ORIGINAL ARTICLE
Cyclin A in nonfunctioning pituitary adenomas Elisa B. Lamback 1 Alexandro Guterres2 Monique Alvares Barbosa3 Carlos Henrique de Azeredo Lima2 Debora Aparecida Silva2 Aline Helen da Silva Camacho2,4 Leila Chimelli2 Leandro Kasuki1,5,6 Mônica R. Gadelha1,2,5 ●
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Received: 15 April 2020 / Accepted: 24 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose Assess cyclin A in nonfunctioning pituitary adenomas (NFPA) and compare its expression in non-invasive and non-proliferative tumors with invasive and proliferative tumors (12× higher risk of recurrence). Methods Quantitative real time polymerase chain reaction to analyze cyclin A using normal pituitary gland as reference. Fold change (FC) > 1 was considered as increased. Tumor invasion was based on Knosp criteria (grades 3–4 considered invasive) and proliferation on the presence of at least two of three criteria: Ki-67 ≥ 3%; mitoses > 2/10; positive p53. Both groups were compared with Mann–Whitney test considering p value < 0.05 as statistically significant. Results Thirty-one patients with NFPA were included. Tumors were mainly of gonadotrophic origin (74.2%), followed by corticotrophic (19.4%) and lactotrophic (3.2%) origins and null-cell adenomas (3.2%). Median tumor diameter was 3.5 cm (1.8–8.0) and Ki-67 was 3.0% (0.3–11%). Sixteen patients had tumors classified as non-invasive and non-proliferative and 15 as invasive and proliferative. Median FC was 0.31 in all tumors (0.13–1.94). Cyclin A was not related to invasion or proliferation (FC 0.41 in non-invasive and non-proliferative tumors and FC 0.30 in invasive and proliferative tumors; p = 0.968). Four (12.9%) patients had tumors that exhibited increased cyclin A [median FC of 1.04 (1.02–1.94)]—three of gonadotrophic origin and one null-cell adenoma, with two tumors classified as non-invasive and non-proliferative and two tumors classified as invasive and proliferative. Median tumor diameter in these samples was 3.4 cm (2.4–3.6) and Ki-67 was 5.1% (2–11%). Conclusions Cyclin A was increased in a minority of NFPA and does not seem to be related to invasion or proliferation. Keywords Nonfunctioning pituitary adenomas Cyclin A Tumorigenesis Proliferation Invasion ●
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Introduction * Mônica R. Gadelha [email protected] 1
Neuroendocrinology Research Center/ Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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Neuropathology and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil
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Radiology Division, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil
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Pathology Division, Instituto Nacional do Câncer, Rio de Janeiro, Brazil
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Neuroendocrinology Division, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil
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Endocrinology Division, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil
Pituitary adenoma
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