Evaluation of expression of somatostatin receptor 1, 2, 3, 5 and dopamine D2 receptor in spindle cell oncocytomas of posterior pituitary
Spindle cell oncocytomas (SCOs) are very rare tumors of the posterior pituitary with potential for locally aggressive behaviour. Their treatment includes surgery and possibly radiotherapy, however other options are lacking. Somatostatin receptors (SSTs) are a possible therapeutic target for somatostatin analogues and their expression has been demonstrated recently in closely related pituicytomas, but there are no data about their presence in SCOs.
We collected five cases of SCO from four patients including one recurrent case. Immunohistochemical detection of TTF1, GFAP, CD68, SST1, SST2, SST3, SST5 and D2 dopamine receptor (D2DR) was performed. Intensity, percentage of positive cells and pattern of expression was evaluated in semiquantitative fashion. Protein expression of SST1−5 and D2DR was further evaluated by western blot.
Mean patient age was 61.8 years (range 47–71 years) with male to female ratio 1:1. In one patient, samples from the original tumor and its recurrence 16 years later were assessed. TTF1 was positive in all five cases, no expression of GFAP and CD68 was seen. Immunohistochemical expression of SST1 was noted in 1/5 cases, SST2 in 2/5 cases, including recurrent case but not the original case. SST3 was expressed in 3/5 tumors and D2 dopamine receptor in 4/5 cases. Western blot was successfully performed in four samples. SST2, SST3 and D2DR expression was identified in all the samples, including two cases originally negative for SST2 and one case negative for SST3 by immunohistochemistry. The number of positive cells and level of expression varied among different areas of the same tumors. No expression of SST5 was observed. In the patient with the recurrent tumor, intensity of SST2, SST3 and D2DR expression varied between original tumor and its recurrence.
We demonstrated presence of different SST subtypes and D2DR in spindle cell oncocytomas. The most commonly expressed subtype was SST2 and SST3, while no expression of SST5 was observed. Expression showed spatial heterogeneity and temporal changes as seen in the recurrent case. The biological meaning of SSTs expression in SCOs is unclear as well as whether it may be exploited in treatment of selected cases.
KeywordsSpindle cell oncocytoma Posterior pituitary Somatostatin receptors Predictive markers
This study was supported by project ASPIRE WII229983 from Pfizer. The funding sources had no impact on the study design, collection, analysis, and interpretation of data, on the writing of the article, or on the decision to submit the article for publication. The authors declare no conflicts of interest. The authors would like to thank prof Dr Ales Ryska and prof Dr Jan Cap for their valuable comments and suggestions to improve the quality of the paper.
- 4.Casar-Borota O, Heck A, Schulz S, Nesland JM, Ramm-Pettersen J, Lekva T et al (2013) Expression of SSTR2a, but not of SSTRs 1, 3, or 5 in somatotroph adenomas assessed by monoclonal antibodies was reduced by octreotide and correlated with the acute and long-term effects of octreotide. J Clin Endocrinol Metab 98(11):E1730–E1739CrossRefGoogle Scholar
- 14.Keskin O, Yalcin S (2013) A review of the use of somatostatin analogs in oncology. Onco Targets Ther 6:471–483Google Scholar
- 17.Klisovic DD, O’Dorisio MS, Katz SE, Sall JW, Balster D, O’Dorisio TM et al (2001) Somatostatin receptor gene expression in human ocular tissues: RT-PCR and immunohistochemical study. Invest Ophthalmol Vis Sci 42(10):2193–2201Google Scholar
- 22.Trott G, Pereira-Lima JF, Leaes CG, Ferreira NP, Barbosa-Coutinho LM, Oliveira MC (2015) Abundant immunohistochemical expression of dopamine D2 receptor and p53 protein in meningiomas: follow-up, relation to gender, age, tumor grade, and recurrence. Braz J Med Biol Res 48(5):415–419CrossRefGoogle Scholar
- 24.Prou D, Gu WJ, Le Crom S, Vincent JD, Salamero J, Vernier P (2001) Intracellular retention of the two isoforms of the D(2) dopamine receptor promotes endoplasmic reticulum disruption. J Cell Sci 114(Pt 19):3517–3527Google Scholar