Ectopic expression of FSH receptor isoforms in neoplastic but not in endothelial cells from pancreatic neuroendocrine tumors.
FSH receptor (FSHR) expression is restricted to gonads, where it drives FSH-dependent cell differentiation; in addition, FSHR plays an important role in the regulation of ovarian angiogenesis. Recently, FHSR expression has been shown in blood vessels of various tumors. However, pancreatic neuroendocrine tumors (p-NET), which have high-degree blood supply, were not included in that study. The aim of this study was to evaluate FSHR expression in p-NET. FSHR expression was evaluated in tumor samples from 30 patients with p-NET by immunohistochemistry and Western blot; fluorescence microscopy was used to localize FSHR in specific cells from tissue samples. von Willebrand factor (vWF) and chromograninA (chrA) was used as blood vessel and NET cells marker, respectively, to co-localize FSHR. FSHR expression was detected in all p-NET by immunohistochemistry. Western blot confirmed FSHR expression on p- NET although different FSHR isoforms, ranging from 240 kD to 55 kD were found in the samples studied. Surprisingly, FSHR co-localized with chrA but not with vWF, suggesting that neoplastic cells of neuroendocrine origin rather than blood vessels expressed FSHR. No relationship was found between degree of FSHR expression and histology of p-NET. FSHR may be aberrantly expressed in neoplastic cells from p-NET and not in tumor blood vessels; however, its biological significance as well as its clinical relevance remains to be elucidated.
Department of Endocrinology, University of Pisa, Pisa, Italy.
C
C
Sardella
D
D
Russo
F
F
Raggi
M
M
Lombardi
C
C
Urbani
S
S
Brogioni
U
U
Boggi
N
N
Funel
B
B
Chifenti
D
D
Campani
G
G
Fanelli
P
P
Marchetti
F
F
Basolo
M T
MT
Locci
E
E
Martino
F
F
Bogazzi
D015153:Blotting, Western; D015331:Cohort Studies; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism*
D020033:Protein Isoforms; D011962:Receptors, FSH