Pituitary adenomas are usually benign
tumors; however, some behave aggressively and metastasize. Until now, no specific marker of aggressive behavior or
malignancy has been found. The polysialylated
neural cell adhesion molecule (
NCAM), which is highly expressed in embryonic tissues such as the brain and pituitary, is detected in some and
neuroendocrine tumors. Because polysialylation has been implicated in the regulation of cell growth and migration, polysialylated
NCAM expression has been considered as a prognostic marker in such
tumors.
METHODS: In the present study, the authors analyzed polysialylated
NCAM expression in 82
pituitary tumors from humans: 49 secreting
adenomas, 32 nonfunctioning
adenomas, and one
growth hormone and
prolactin-secreting
carcinoma associated with
acromegaly and spinal and liver
metastases. Based on immunohistochemical analyses, the
tumors were classified as somatotropic (22
tumors),
prolactinoma (14
tumors), corticotropic (17
tumors), and gonadotropic or so-called null cell
adenomas (28
tumors). Assessment of polysialylated
NCAM was performed using three different methods (immunohistochemical analysis, Western blot analysis, and
enzyme-linked
immunosorbent assay) with a specific mouse monoclonal
immunoglobulin M (Men B) that recognizes
polysialic acid on
NCAM. Tumoral
NCAM expression was also evaluated with the aid of immunohistochemical analysis. Using this method,
NCAM and polysialylated
NCAM were studied in six healthy pituitaries. In addition, correlations were investigated using three statistical methods (chi-square test, nonparametric Mann-Whitney U-test, and principal component analysis) to compare tumoral polysialylated
NCAM expression and seven parameters (
tumor size and type, intrasphenoidal or cavernous sinus invasion, Ki-67 index, mitoses, and patient age and sex).
Neural cell adhesion molecules were expressed in the healthy anterior pituitary and in all
tumors. In contrast, polysialylated
NCAM was not found in the healthy pituitary gland, but was expressed in 46.3% of typical
pituitary tumors and 85% of the
tumors selected as highly aggressive, including one
carcinoma and three
tumors with histological characteristics that raised suspicion of
malignancy. There was no significant correlation between polysialylated
NCAM expression and
tumor size,
tumor type, Ki-67 index, mitoses, or patient age and sex. In contrast, the expression of polysialylated
NCAM, which was sensitive to
endoneuraminidase-N treatment, was strongly correlated with
tumor invasion (p < 0.0001).
CONCLUSIONS: