Morita Koji, Takano Koji, Yasufuku-Takano Junko, Yamada Shozo, Teramoto Akira, Takei Mao, Osamura Robert Yoshiyuki, Sano Toshiaki, Fujita Toshiro
Department of Nephrology and Endocrinology, University of Tokyo Faculty of Medicine, Tokyo, Japan.
Clin Endocrinol (Oxf). 2008 Mar;68(3):435-41. doi: 10.1111/j.1365-2265.2007.03062.x. Epub 2007 Dec 7.
Apart from the constitutively activating mutation of the G-protein alpha subunit (Gsalpha) (gsp mutation), factors involved in tumorigenesis or those in tumour behaviour remain elusive in sporadic GH-secreting pituitary adenomas. Recently, the N-terminally truncated form of fibroblast growth factor receptor-4 (ptd-FGFR4) was identified in pituitary adenomas. This aberrant receptor has transforming activity, and causes pituitary adenomas in transgenic mice. The clinical relevance of this receptor warrants investigation. Our objective was twofold: first, to examine how the expression of ptd-FGFR4 relates to gsp mutations; and second, to see whether patients with this receptor have unique clinical characteristics.
mRNA was extracted from excised adenomas of 45 Japanese acromegalic patients. ptd-FGFR4 expression and gsp mutations were determined by reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing. Preoperative clinical data were collected by reviewing medical charts and pituitary magnetic resonance imaging (MRI) scans.
ptd-FGFR4 mRNA expression was detected in 19 out of 45 tumours (42.2%) while gsp mutations were detected in 25 out of 45 tumours (55.6%). The prevalence of ptd-FGFR4 expression did not differ between gsp-positive (44.0%) and gsp-negative (40.0%) tumours (P = 1.00). ptd-FGFR4-positive tumours invaded the cavernous sinus more frequently (P = 0.0098) than did the ptd-FGFR4-negative tumours. Tumour size was not statistically different between ptd-FGFR4-positive and -negative tumours (P = 0.198). The presence of ptd-FGFR4 did not correlate with age at operation, sex, preoperative serum GH or IGF-1 levels.
We found that ptd-FGFR4 expression and gsp mutations occur independently of each other, and that ptd-FGFR4 expression is associated with more invasive tumours in patients with GH-secreting pituitary adenomas.
除了G蛋白α亚基（Gsα）的组成性激活突变（gsp突变）外，散发性生长激素分泌型垂体腺瘤中参与肿瘤发生的因素或肿瘤行为相关因素仍不明确。最近，在垂体腺瘤中发现了成纤维细胞生长因子受体4（ptd-FGFR4）的N端截短形式。这种异常受体具有转化活性，并在转基因小鼠中引发垂体腺瘤。该受体的临床相关性值得研究。我们的目标有两个：第一，研究ptd-FGFR4的表达与gsp突变之间的关系；第二，观察携带该受体的患者是否具有独特的临床特征。
从45例日本肢端肥大症患者切除的腺瘤中提取mRNA。通过逆转录聚合酶链反应（RT-PCR）和直接测序确定ptd-FGFR4表达和gsp突变。通过查阅病历和垂体磁共振成像（MRI）扫描收集术前临床数据。
45个肿瘤中有19个（42.2%）检测到ptd-FGFR4 mRNA表达，45个肿瘤中有25个（55.6%）检测到gsp突变。ptd-FGFR4表达的发生率在gsp阳性（44.0%）和gsp阴性（40.0%）肿瘤之间没有差异（P = 1.00）。ptd-FGFR4阳性肿瘤比ptd-FGFR4阴性肿瘤更频繁地侵犯海绵窦（P = 0.0098）。ptd-FGFR4阳性和阴性肿瘤之间的肿瘤大小没有统计学差异（P = 0.198）。ptd-FGFR4的存在与手术年龄、性别、术前血清生长激素或胰岛素样生长因子-1水平无关。
我们发现ptd-FGFR4表达和gsp突变相互独立发生，并且在生长激素分泌型垂体腺瘤患者中，ptd-FGFR4表达与更具侵袭性的肿瘤相关。
