[1934] Mass-Spectrometry-Based Proteinomic Analysis of Amyloid Deposits in Pituitary Prolactinomas

S Kip, B Scheithauer, L Erickson, R Lloyd, A Dogan. Mayo Clinic, Rochester, MN

Background: Amyloid deposits are rarely seen in pituitary adenomas, mainly prolactinomas. Published data indicate that the amyloid is produced by endocrine rather than mesenchymal cells. Relative to amyloidogenic peptide components of prolactinomas, it has been suggested that amyloid masses contain prolactin.
Design: We report a retrospective study involving 18 prolactinomas associated with amyloid deposits, all operated between 01/1996 and 03/2009, and nearly half being consultation cases.
Results: The study group showed a M:F ratio of 2:1, mean age of both being 46 yrs. Although marked hyperprolactinemia was noted in all, levels were 4x higher in males (2302 ng/mL) than females (552 ng/mL). Respective tumor sizes were 2.82 cm3 vs. 0.45 cm3. Of note in 6 cases were spherical, concentric deposits, with radial cracking; 12 lesions featured amorphous intercellular deposits. Both were eosinophilic and, where performed (n=3), Congo Red-positive and birefringent. IHC showed intense Golgi-pattern staining for prolactin (n=12). Ultrastructural analysis revealed 10-13 nm fibrils forming stellate extracellular deposits and grouped in intracytoplasmic bundles (n=2). The amyloid deposits were microdissected from H&E slides and analyzed by mass spectrometry (MS). In all cases, prolactin precursor protein was represented, in conjunction with other known amyloidogenic peptides. Although peptide coverage for prolactin varied slightly among cases, all possible tryptic peptides were identifiable, suggesting that the whole prolactin protein, with the exclusion of most of signal peptide (SP), was the major constituent. Interestingly, last 2 of 28 residues of SP, normally cleaved off, were retained, an observation of unknown physiologic significance. Also, almost all prolactin precursor peptides analyzed showed oxidation of 3 residues at the same location, a finding of unknown significance, perhaps attributable to storage artifact. In one patient, growth hormone precursor was also highly represented, maybe related to high frequency of co-expression of these hormones in a subset of adenomas. Also of note was the presence of structural proteins in small quantities.
Conclusions: Ours is the first in depth, sizeable study of pituitary adenomas showing amyloid deposits in which their protein signature was assessed by MS. The findings indicate that, almost the entire prolactin protein, with the exclusion of most of SP, is deposited by the hormone-secreting tumor cells and comprise the major component of the amyloid.
Category: Techniques

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 256, Monday Morning

 

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