Correlative immunohistochemical and reverse transcriptase polymerase chainreaction analysis of somatostatin receptor type 2 in neuroendocrine tumorsof the lung

Somatostatin receptors type 2 (sst2) have been frequently detected in neuro endocrine tumors and bind somatostatin analogues, such as octreotide, with high affinity. Receptor autoradiography, specific mRNA detection and, more recently, anti-sst2 polyclonal antibodies are currently employed to reveal sst2. The aim of the present study was to investigate by three different te chniques the presence of sst2 in a series of 26 neuroendocrine tumors of th e lung in which fresh frozen tissue and paraffin sections were available. I t was possible, therefore, to compare, in individual cases, RNA analysis st udied by reverse transcriptase polymerase chain reaction (RT-PCR), in situ hy bridization (ISH), and immunohistochemistry. A series of 20 nonneuroendo crine lung carcinoma samples served as controls. RT-PCR was positive for ss t2 in 22 of 26 samples, including 15 of 15 typical carcinoids, 5 of 6 atypi cal carcinoids, and 2 of 5 small-cell carcinomas. The sst2 mRNA signal obta ined by RT-PCR was strong in the majority (87%) of typical carcinoids and o f variable intensity in atypical carcinoids and small-cell carcinomas. A we akly positive signal was observed in 5 of 20 control samples. In immunohist ochemistry, two different antibodies (anti-sst2) were employed, including a monoclonal antibody, generated in the Department of Pathology, University of Turin. In the majority of samples a good correlation between sst2 mRNA l as detected by RT-PCR) and sst2 protein expression las detected by immunohi stochemistry) was observed. However, one atypical carcinoid and one small-c ell carcinoma had focal immunostaining but no RT-PCR signal. ISH performed in selected samples paralleled the results obtained with the other techniqu es. A low sst2 expression was associated with high grade neuroendocrine tum ors and with aggressive behavior. It is concluded that 1) neuroendocrine tu mors of the lungs express sst2, and there is a correlation between the mRNA amount and the degree of differentiation; 2) immunohistochemistry and ISH are reliable tools to demonstrate sst2 in these tumors; and 3) sst2 identif ication in tissue sections may provide information on the diagnostic or the rapeutic usefulness of somatostatin analogues in individual patients with n euroendocrine tumors.