Expression of the human growth hormone in normal tissues and tumors; A Tissue Microarray-Study on 9.507 samples

Abstract

Growth hormone (GH) is a polypetide hormone secreted by the somatotroph cells of the anterior pituitary and the cells of the syncytiotrophoblast during gestation. The sequence from GH synthesis, including its anatomical and molecular basis, to its cellular and IGF (Insulin-like growth factor) mediated actions is termed the ’GH-IGF axis’ and has been studied since more than a century. The main action of GH is on the longitudinal growth and metabolic regulation. Its peripheral receptors are almost ubiquitous but expressed in majority in the liver and adipose tissues. The extra-pituitary expression of growth hormone by normal and malignant tissues has already been investigated in the literature because of the potential role of GH in tumourigenesis due to its anabolic effect. However, no consensus could be reached because of the scarcity and the heterogeneity of the different studies published. In order to clarify whether GH is indeed specific to the pituitary gland and its adenomas or whether other malignant and non-malignant tissues can ectopically express growth hormone, we analyzed a cohort of more than 8899 tumor tissue samples from 115 different tumor types and subtypes as well as 76 non-neoplastic tissue categories by immunohistochemistry in a tissue microarray format. In non-malignant tissues, a strong cytoplasmatic growth hormone staining was only found in the trophoblastic cells of the placenta and in the epithelial cells of the adenohypophysis. In tumors, cytoplasmic growth hormone staining was seen in 3 of 3 analyzed pituitary adenomas, known to overexpress GH clinically. Growth hormone immunostaining was, however, not seen in any of the 7.643 extrapituitary tumors from 115 different cancer types and subtypes. The results of this study show the high specificity of growth hormone antibody we used for the anterior pituitary and the syncytiotrophoblast cells, and the exceptionally high specificity of the expression of this hormone by these tissues. This study emphasizes the usefulness of the TMAs technique in the task of identifying new, promising tumor markers.