We discussed the 2 published cases and describe another case of poorly-differentiated plurihormonal PIT-1 positive adenoma with moderate SSTR2 expression and intense STTR5 expression succeffuly treated with PAS-LAR 40mg/month.
SSTR2A expression was higher compared to gonadotroph and nonfunctioning pituitary adenomas (<i>p</i> = 0.0217 and 0.0126, respectively) while PIT-1-positive adenomas showed even higher SSTR2A expression (<i>p</i> < 0.0001).
Our data suggests that Pit-1 can be utilized as a second tier immunostain in cases of clinically non-functioning adenomas that are immunonegative for ACTH, prolactin, growth hormone, TSH, and SF-1 in order to further segregate rare cases of Pit-1-positive adenomas from null cell adenomas.
RT-qPCR analyses were performed to assess the transcriptional pattern of PROP1, POU1F1, TBX19, and hormone-producing genes in tissue samples of corticotrophinomas (n=10), somatotrophinomas (n=8), and nonfunctioning adenomas (n=6).
Interestingly, these adenomas showed very high expression levels of PIT1, a transcriptional factor that regulates the gene expression of Gh, Prl, Ghrhr and Pit1 itself, playing a key role in pituitary gland development and physiology.
The functional differentiation of pituitary cells and adenomas follows the combination of transcription factors and co-factors in three cell lineages [growth hormone-prolactin-thyroid-stimulating hormone lineage, adrenocorticotrophic hormone (ACTH)/pro-opiomelanocortin (POMC) lineage, and follicular stimulating hormone (FSH)/luteinizing hormone (LH) lineage], which include Pit-1, GATA-2, SF-1, NeuroD1/beta2, Tpit, ERalpha, and others.
NeuroD1 mRNA was widely expressed in PA (82%), with measurable levels found especially in those derived from Pit-1 independent lineages, i.e. corticotroph (5/5) and clinically non-secreting (CNS) adenomas (9/11).
These results suggested that GATA-2 contributes to the functional expression and the differentiation of Gn-su-positive adenomas and the TSH-secreting adenomas and that the interaction between GATA-2 and Pit-1 can lead to gene-specific action and differentiation of TSH-secreting adenomas.
Competitive RT-PCR assay could distinguish silent adenomas of the Pit-1 group from the other nonfunctioning adenomas in the expression levels of Pit-1 and GHRH-R mRNAs.
Eighteen pituitary adenomas and three normal pituitary glands were examined for the expression of PROP1 and POU1F1 by using RT-PCR Pituitary adenomas were diagnosed as non-functioning adenomas (n = 11), prolactinomas (n=5), GH-producing adenoma (n = 1) and ACTH-producing adenoma (n = 1).
Three nuclear transcriptional factors, AP-1, CREB, and Pit-1, which are targets of protein kinase C and A, appear to play critical roles in both neoplastic growth and hormone secretion in hormone-producing adenomas.
Nine clinically non-functioning adenomas expressed Pit-1 as well as GH, PRL and/or TSH beta, thus having somatomammotrophic or thyrotrophic properties, 3 of which overlapped with the above DAX-1-expressing adenomas.
Although there were no GH, PRL or TSH-beta transcripts in Pit-1 mRNA-negative ACTH cell and non-functioning adenomas, PRL mRNA was detected in all Pit-1 mRNA-positive ACTH cell adenomas and GH, PRL and/or TSH-beta mRNA were found in four of seven Pit-1 mRNA-positive non-functioning adenomas.
On the other hand, ER mRNA was detected in 14 (94%) of adenomas studied. mRNAs of Pit-1 and ER were detected more frequently than immunohistochemical expression of their products.
Therefore, the presence of unknown transcriptional factor other than Pit-1, common to GH, PRL, and ACTH, may be speculated to be expressed in this adenoma.
Only the 10 adenomas that did not express pit-1 mRNA were subjected to further analysis by polymerase chain reaction amplification of the adenoma reverse transcriptase products for the activin/inhibin beta B-, beta A-. and alpha-subunits.
Pit-1 is overexpressed (2.5- to 5-fold) in the PRL- and GH-secreting tumors, but to an extent consistent with the predominant cellular type of these adenomas.
Pit-1 activity was anticipated in prolactin- and GH-secreting adenomas, but was also detected in a proportion of endocrine-inactive (non-secreting) adenomas that did not express Pit-1 target genes.
Taken together, the data confirm that Pit-1/GHF-1 expression is restricted to GH-, prolactin- and TSH-expressing cells, and the increased expression in adenomas is compatible with a role of Pit-1/GHF-1 in cell proliferation.
The expression of Pit-1 mRNA in a small fraction of null and alpha-subunit only tumors indicates that there may be a previously unsuspected diversity of origin within these particular subsets of adenomas.