Immunohistochemical detection of somatostatin receptor subtypes in “clinically nonfunctioning” pituitary adenomas

Abstract

Pituitary tumors diagnosed before surgery as "non-functioning" in fact represent a heterogenous group, the majority of which express glycoprotein hormones or their free subunits. It is known that some of them expresses somatostatin receptors, but the data available until now rarely refer to the receptor subtype. Five different subtypes of somatostatin receptors (sst1-5) have been cloned. We studied 18 pituitary tumors diagnosed before surgery as "non-functioning." After the surgery the tumors were immunostained with antibodies against pituitary hormones and alpha subunit as well as with antibodies against the somatostatin receptor proteins 1-5. Thirteen adenomas expressed immunoreactivity for FSH, LH, and/or alpha subunit and were classified as gonadotroph adenomas. The remaining five adenomas were immunonegative for all the examined pituitary hormones and were diagnosed as null cell adenomas. All the adenomas of both the groups showed immunopositivity for at least three receptor subtypes. The strongest immunopositivity was found in both groups with anti-sst1 and anti-sst5 antibodies. The marked immunopositivity was also revealed in both groups with anti-sst2B antibody. On the other hand, the sst2A immunopositivity was weak or absent in a majority of tumors. The main difference between two groups was in the sst4 receptor subtype which was absent in all but two gonadotroph adenomas but present in all but one null cell adenoma. These findings suggest that "non-functioning" pituitary adenomas are potential candidates for therapy with somatostatin analogs targeted mainly to the receptor subtypes 1 and 5.

SSTR3 is a putative target for the medical treatment of gonadotroph adenomas of the pituitary

“…Using polyclonal anti-SSTRs antibodies, Pawlikowski et al (2003) reported high expression of SSTR1, SSTR2, and SSTR5, with only little or no expression of SSTR3 in 13 GPAs and five null cell adenomas. The same group later found SSTR3 to be the most commonly expressed subtype in GPAs, followed by SSTR2, with no expression of SSTR5 (Pisarek et al 2009).…”

“…Previous studies assessing expression of SSTR2 in GPAs have produced conflicting results (Pawlikowski et al 2003, Pisarek et al 2009, Ramirez et al 2012. Therefore, we aimed to determine the expression profile of SSTR2, SSTR3, and SSTR5 in a large and homogeneous cohort of patients with primary or recurrent GPAs.…”

Pasireotide, a multiple somatostatin receptor subtypes ligand, reduces cell viability in non-functioning pituitary adenomas by inhibiting vascular endothelial growth factor secretion

“…Indeed, almost all human tumors express SSTR1 mRNA (Patel 1997), suggesting that compounds also targeting SSTR1, such as pasireotide, might represent a good tool for the control of neoplastic growth. Moreover, an immunohistochemical study demonstrated that SSTR1 is one of the most expressed SSTR subtypes in NFA (Pawlikowski et al 2003). Therefore, stable SRIF analogs binding with high affinity to SSTR1, whether selectively or together with other SSTR subtypes, may indeed open a new frontier in the treatment of NFA.…”

Ocena efektów leczenia analogami somatostatyny nieczynnych hormonalnie gruczolaków przysadki w porównaniu z akromegalią

“…As far as secondary therapy (i.e. therapy applied after the surgical intervention) is concerned, the use of somatostatin analogues (SSA) is proposed, considering the presence of somatostatin receptors (SSTR) in NFPA [5,6]. Receptor scintigraphy and possibly immunohistochemistry should be performed for the purpose of SSTR detection [7].…”