Endocrine Abstracts

Recent advances in molecular pathology have improved our knowledge on the pathogenesis of pituitary tumors, as well as on their growth potential, likelihood of recurrence, and prognosis. The development of reliable and prognostically informative methods of assessing tumor behavior is particularly important in pituitary tumors, where no precise correlation exists between morphology and clinical aggressiveness. Specific morphologic features (macroscopic invasion of the perisellar tissues, number of mitoses, Ki-67 labelling index, p53 expression) may serve as predictive markers of tumor behavior.

Apoptosis and mitoses represent two adverse and asynchronous events, maintaining the optimal cell numbers, and, as well as cytogenetic analysis, may be useful in defining the biological aggressiveness of pituitary tumors. From the genetic point of view, MEN1 tumors seem more aggressive, invasive and resistant to treatment requiring a very careful long-life follow-up. Recently, several studies attempted to identify new molecular markers (i.e. cyclooxygenase-2, galectin-3, angiogenesis molecules, pituitary tumor-transforming gene), that need to be validated. Among these, several are represented by therapeutic targets of new (and old) molecularly targeted therapies. Immunohistochemical detection of somatostatin receptors is important, being their density directly related to the effectiveness of somatostatin analogues. Similarly, the outcome of treatment with temozolomide, an orally administered alkylating agent, has been related to the expression of O(6)-methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme. Studies involving cDNA microarrays, stem cells and microenvironment may reveal additional important information to identify predictive markers in the near future.