Naslov
Pituitary Adenoma and the Chemokine Network: A Systemic View

Autori
Grizzi, Fabio ; Borroni, EllenaMaria ; Vacchini, Alessandro ; Qehajaj, Dorina ; Liguori, Maria ; Štifter, Sanja ; Chiriva-Internati, Maurizio ; Di Ieva, Antonio

Izvornik
Frontiers in endocrinology (Lausanne) (1664-2392) 11 (2015); 141, 6

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, znanstveni

Ključne riječi
pituitary adenoma ; chemokine network

Sažetak
Pituitary adenomas (PAs) are adenohypophysial neoplasms, representing ~10–15% of all intracranial tumors, which are found to occur in almost 20% of the general population (1, 2). Although recognized as benign lesions, 20–45% of PAs are invasive and some exhibit clinically aggressive behavior (1, 3). Advancements have allowed the pathological classification of PAs from a histochemical classification (i.e., acidophilic, basophilic, and chromophobic PAs) to an immunohistochemical-based one, which essentially recognizes PAs as lactotrophic, somatotrophic, corticotrophic, gonadotrophic, thyrotrophic, and null cell adenomas (4). Electron microscopy has identified additional subtypes, based on the appearance of specific morphology/arrangement of ubiquitous cytoplasmic constituents (5). It is now accepted that the hypothalamic–anterior pituitary axis integrates a set of stimulatory and inhibitory central and peripheral signals to synthesize and secrete hormones by highly differentiated cell types, namely somatotrophs, gonadotrophs, lactotrophs, thyrotrophs, and corticotrophs. Each of these cell types expresses unique G protein-coupled receptors (GPCRs), which are specific for hypothalamic releasing and inhibiting hormones. These peptides traverse the vascular system that connects the hypothalamus with the anterior pituitary gland and impinge upon the pituitary cells to regulate the synthesis and secretion of anterior pituitary hormones (6). It has been demonstrated that PAs arise from any of these cells as monoclonal neoplasms (7). The functional classification of PAs has also been facilitated by the measurement of circulating trophic and target hormone concentrations (6). Several hallmarks of PAs (i.e., benign nature, slow growth) point to a unique growth behavior distinct from that of other endocrine and non- endocrine malignancies (8). The general failure to proceed to true malignancy with demonstrable extra-cranial metastases remains an intriguing feature not completely investigated yet (8). Atypical and/or aggressive PAs can share some histological features with carcinomas, including atypical morphologic appearances, elevated mitotic index (i.e., Ki-67 labeling index >3%), or extensive nuclear staining for p53 (9). Nonetheless, the endocrine signs due to hormonal hypersecretion or pituitary deficit, pituitary abnormal growth, or invasion represent a greater clinical and therapeutic challenge (8). The subset of PAs with clinically aggressive behavior should be promptly identified, as patients with such tumors might require closer clinical, biochemical, and imaging surveillance or multimodal therapeutic treatments. Despite the paramount importance of identifying specific criteria for tumor aggressiveness, no clinical signs, biochemical biomarkers, or imaging techniques have been universally accepted and no reliable histological biomarker or classification system for characterizing pituitary aggressive neoplasms are available today (10). It has also been suggested that the histological features of “typical” and “atypical” PAs as defined by the World Health Organization (WHO) do not entirely correlate with clinical outcome. In particular, some typical PAs have an aggressive behavior while many atypical PAs lack an aggressive clinical dynamics (1, 7). Additionally, the lack of standardization of the terminology in the literature remains a source of confusion (i.e., the terms “aggressive” and “invasive” are often used synonymously).

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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