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

Clinicopathology, clonality, and hormone production profile of prolactinoma

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。

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 (16~65) 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 coefficien t =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.