Endocrine Abstracts

Somatotroph adenomas (SA) causing acromegaly exist as two major pathological variants: densely and sparsely granulated, according to the number and distribution of growth-hormone-containing secretory granules. These variants are increasingly recognised by neuropathologists and endocrinologists, but the consequences for tumour behaviour and patient outcome remain to be defined. Sparsely granulated SAs are associated with younger, female patients and are more invasive and proliferative than densely granulated SAs. In order to invade surrounding structures tumour cells must switch from a polarised, static, epithelial-like phenotype to a motile, proliferative mesenchymal-like phenotype. This process, termed epithelial-mesenchymal transition (EMT), is a feature of many invasive and metastatic neoplasms. Here we hypothesise that a change in phenotype from epithelial-like towards mesenchymal-like underlies the more invasive and proliferative behaviour of sparsely granulated SAs. We examined the expression of markers and mediators of EMT in a series of SAs (n=21) stratified by granulation pattern and compared the findings to clinical and biochemical characteristics. Sparsely granulated SAs were significantly (P<0.05) larger than densely granulated SAs. There was no significant difference in preoperative plasma IGF1 or growth hormone concentrations, sex or age in this series. However, quantification of a panel of EMT-related targets revealed that sparsely granulated SAs expressed significantly more mRNA encoding ZEB1 (Zinc Finger E-Box Binding Homeobox 1) and VIM (vimentin), consistent with EMT-like changes. In addition, protein components of the adherens junction (E-cadherin, α-catenin, β-catenin, JUP, p120) were expressed in densely granulated SAs, but were completely absent in sparsely granulated SAs. These findings suggest that lack of a functional adherens junction, along with a more mesenchymal-like pattern of mRNA expression, may contribute to the more invasive behaviour of sparsely granulated SAs, and that restoration of the adherens junction may offer the possibility to inhibit the more rapid growth of sparsely granulated SAs.