IngentaConnect Expression of pituitary tumour-derived, N-terminally truncated is...

Authors: Morita, Koji¹; Takano, Koji¹; Yasufuku-Takano, Junko¹; Yamada, Shozo²; Teramoto, Akira³; Takei, Mao³; Osamura, Robert Yoshiyuki⁴; Sano, Toshiaki⁵; Fujita, Toshiro¹

Source: Clinical Endocrinology, Volume 68, Number 3, March 2008 , pp. 435-441(7)

Publisher: Blackwell Publishing

Abstract:

Summary Objective

Apart from the constitutively activating mutation of the G-protein alpha subunit (Gsα) (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. Materials and methods

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. Results

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. Conclusions

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.

Document Type: Research article

DOI: 10.1111/j.1365-2265.2007.03062.x

Affiliations: 1: Department of Nephrology and Endocrinology, University of Tokyo Faculty of Medicine, Bunkyo-ku, Tokyo, 2: Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Minato-ku, Tokyo, 3: Department of Neurosurgery, Nippon Medical School, Bunkyo-ku, Tokyo, 4: Department of Pathology, Tokai University School of Medicine, Isehara-shi, Kanagawa and 5: Department of Pathology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho, Tokushima, Japan

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Expression of pituitary tumour-derived, N-terminally truncated isoform of fibroblast growth factor receptor 4 (ptd-FGFR4) correlates with tumour invasiveness but not with G-protein alpha subunit (gsp) mutation in human GH-secreting pituitary adenomas