The molecular pathogenesis of
prolactinomas has resisted elucidation; with the exception of a RAS mutation in a single aggressive
prolactinoma, no mutational changes have been identified. In
prolactinomas, a further obstacle has been the paucity of surgical specimens suitable for molecular analysis since prolactionomas are infrequently removed due to the availability and effectiveness of medical
therapy. In the absence of mutational events, gene expression changes have been sought and detected. Using high-throughput analysis from a large bank of human
pituitary adenomas, we examined these
tumors according to their molecular profiles rather than traditional immunohistochemistry. We examined six
prolactinomas and eight normal pituitary glands using
oligonucleotide GeneChip microarrays, reverse transcription-real time quantitative polymerase chain reaction using 10
prolactinomas, and proteomic analysis to examine
protein expression in four
prolactinomas. Microarray analyses identified 726 unique genes that were statistically significantly different between
prolactinomas and normal glands, whereas proteomic analysis identified four differently up-regulated and 19 down-regulated
proteins. Several components of the Notch pathway were altered in
prolactinomas, and there was an increased expression of the
Pit-1 transcription factor, and the survival factor BAG1 but decreased
E-cadherin and
N-cadherin expression. Taken together, expression profiling and proteomic analyses have identified molecular features unique to
prolactinomas that may contribute to their pathogenesis. In the current era of molecular medicine, these findings greatly enhance our understanding and supercede immunohistochemical diagnosis.