Markers to predict tumor biology represent an important tool for the optimal management of pituitary adenomas. Specific morphologic features may serve as predictive markers of tumor behavior. These include a) tumor cell-specific markers, b) stromal-related elements involving vasculature and angiogenetic factors, and additional stromal substances and c) miscellaneous tumor type-associated features.
Macroscopic invasion of the perisellar tissues, defined as radiographic or gross operative finding, is considered a more consistent prognostic indicator. Regarding morphology, cytologic atypia is not a reliable feature. In contrast, the number of mitoses is very important for prognosis. Given that only scarce mitoses can be identified, particularly in some aggressive cases, the Ki-67 represents an alternative key feature to assess tumor proliferation. In the recent WHO classification, the Ki-67 labeling index (LI) represents a major prognostic indicator for pituitary adenomas. In addition, expression of the p53 gene product is very important marker to access tumor biology. Adenomas with more than 3% Ki-67 LI and extensive p53 immunoreactivity are classified as atypical adenomas. Some investigators have proposed to designate adenomas as atypical when Ki-67 LI is more than 10% irrespectively of p53 status
Apoptosis and mitoses represent two adverse and asynchronous events, which under physical conditions maintain the optimal cell numbers. Apoptoses can be recognized by histology alone. Using DNA labeling techniques we can identify apoptotic cells, higher apoptotic labeling index was found in functioning compared to nonfunctioning adenomas, in microadenomas, particularly in corticotroph adenomas, and in untreated adenomas, particularly prolactinomas.
Cytogenetic analysis of chromosomes may provide important information regarding tumor development and progression. Increased chromosome 11 copies are more frequent in functioning, aneuploid pituitary adenomas. Monosomy or partial loss of chromosome 11 in adenomas with normal or increased DNA labeling index indicates complex genomic abnormalities of chromosomes, other than chromosome 11.
Immunohistochemical detection of somatostatin receptors is important, as their density in the cytoplasmic membrane is directly related to the effectiveness of somatostatin analogues. Therefore, morphologic assessment of the somatostatin receptor profile can predict the responsiveness and also validate the effectiveness of treatment with somatostatin analogues.
New drugs such as temozolomide can be used to treat aggressive pituitary tumors. 06 ethylguanine DNA methyltransferase (MGMT) serves as a predictive marker for this new option of treatment. It is important to know that only patients with adenomas showing low MGMT levels respond, whereas those with high levels are resistant to temozolomide therapy.
We can conclude that several predictive factors are currently available that may be applied using morphologic methods.
25 - 29 Apr 2009
European Society of Endocrinology