Lamback Elisa B, Guterres Alexandro, Barbosa Monique Alvares, Lima Carlos Henrique de Azeredo, Silva Debora Aparecida, Camacho Aline Helen da Silva, Chimelli Leila, Kasuki Leandro, Gadelha Mônica R
Neuroendocrinology Research Center/ Endocrinology Division, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Neuropathology and Molecular Genetics Laboratory, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.
Endocrine. 2020 Nov;70(2):380-387. doi: 10.1007/s12020-020-02402-5. Epub 2020 Jul 3.
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).
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.
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%).
Cyclin A was increased in a minority of NFPA and does not seem to be related to invasion or proliferation.
评估细胞周期蛋白A在无功能垂体腺瘤（NFPA）中的表达，并比较其在非侵袭性和非增殖性肿瘤与侵袭性和增殖性肿瘤（复发风险高12倍）中的表达情况。
采用定量实时聚合酶链反应，以正常垂体为参照分析细胞周期蛋白A。将变化倍数（FC）>1视为表达增加。肿瘤侵袭依据Knosp标准（3 - 4级视为侵袭性），增殖依据三个标准中至少两个标准的存在情况：Ki-67≥3%；有丝分裂>2/10；p53阳性。两组采用Mann-Whitney检验进行比较，将p值<0.05视为具有统计学意义。
纳入31例NFPA患者。肿瘤主要起源于促性腺激素细胞（74.2%），其次是促肾上腺皮质激素细胞（19.4%）、催乳素细胞（3.2%）起源以及无功能细胞腺瘤（3.2%）。肿瘤中位直径为3.5 cm（1.8 - 8.0），Ki-67为3.0%（0.3 - 11%）。16例患者的肿瘤被分类为非侵袭性和非增殖性，15例为侵袭性和增殖性。所有肿瘤的中位FC为0.31（0.13 - 1.94）。细胞周期蛋白A与侵袭或增殖无关（非侵袭性和非增殖性肿瘤的FC为0.41，侵袭性和增殖性肿瘤的FC为0.30；p = 0.968）。4例（12.9%）患者的肿瘤细胞周期蛋白A表达增加[中位FC为1.04（1.02 - 1.94）]，其中3例起源于促性腺激素细胞，1例为无功能细胞腺瘤，2例肿瘤被分类为非侵袭性和非增殖性，2例为侵袭性和增殖性。这些样本中的肿瘤中位直径为3.4 cm（2.4 - 3.6），Ki-67为5.1%（2 - 11%）。
少数NFPA中细胞周期蛋白A表达增加，且似乎与侵袭或增殖无关。
