垂体泌乳素腺瘤患者的激素分泌谱、克隆状态及临床病理学分析

目的探讨影响垂体泌乳素瘤生物学行为的因素。方法123例垂体泌乳素腺瘤患者,其中男40例,女83例。将123例患者的肿瘤组织镜下标本经10%福尔马林或70%乙醇固定,进行常规病理及免疫组化分析。测定123例患者肿瘤切除前后的血清泌乳素水平。对26例女性患者肿瘤组织标本提取的DNA进行了HUMARA分析,确定肿瘤的克隆状态。结果123例患者中单激素分泌性61例(50%),多激素分泌性62例(50%)。患者年龄大小与血清泌乳素水平呈正相关(ρ=0.337,P<0.01),患者年龄与肿瘤体积呈正相关(ρ=0.378,P<0.01),肿瘤体积与血清泌乳素水平呈正相关(ρ=0.670,P<0.01)。多元回归分析提示,只有肿瘤体积与血清泌乳素水平存在明显相关。Mann-WhitneyU检验提示,泌乳素水平越高肿瘤体积越大,患者年龄越大,肿瘤侵袭海绵窦越明显。男性患者血清泌乳素水平明显高于女性患者,同时肿瘤体积明显较大。11例患者多激素分泌性垂体泌乳素腺瘤为单克隆起源。结论垂体泌乳素腺瘤患者除了分泌泌乳素外,还可以分泌多种垂体激素,而且绝大多数多激素分泌性垂体腺瘤的起源是单克隆性的。

Clinicopathology, clonality, and hormone production profile of prolactinoma

OBJECTIVE: To analyze the hormone production profiles of prolactinoma and to analyze the clonality of prolactinoma. METHODS: Clinicopathologic factors were studied in 123 patients with prolactinoma, 40 males and 83 females, aged 31.9 +/- 12.2 (16 approximately 65) who underwent resection of tumor in Japan. The specimens were fixed in either 10% neutral buffered formalin or 70% alcohol and used for light microscopy. DNA was extracted from 26 samples of alcohol-fixed tissue from female patients for human androgen receptor gene (HUMARA) assay. The data underwent Spearman rank correlation analysis and nonparametric Mann-Whitney U test. RESULTS: sixty-one cases (50%) were pure prolactinoma and 62 cases (50%) were plurihormonal prolactinoma. Spearman rank correlation analysis revealed that age was significantly positively correlated with serum prolactin (PRL) level (P = 0.0002), and tumor volume (P < 0.0001); and tumor volume was significantly positively correlated with serum PRL level (P < 0.0001). Multiple regression analysis showed a significant correlation only between tumor volume and serum PRL level (multiple correlation coefficient = 0.622, coefficient of multiple determination = 0.387, t = 7.59, P < 0.0001). Mann-Whitney U test revealed that the invasiveness of tumor was significantly positively correlated with the serum PRL level (P < 0.0001), volume of tumor (P < 0.0001), and the age of patient (P = 0.0003); that the sex of patient was significantly positively correlated with the pre-and post-operative serum PRL levels (both P < 0.0001) and the tumor volume (P < 0.0001); and that male patients had significantly higher PRL levels and larger adenomas(P < 0.0001, P < 0.0001 respectively). The HUMARA assay disclosed that 11 of the 13 plurihormonal prolactinomas (85%) were compatible with monoclonal origin. CONCLUSION: Prolactinoma secrets not only PRL but also other pituitary hormones. Most multihormone producing prolactinomas are monoclonal in origin.