Somatostatin Receptor Subtypes 2 and 5 Are Associated with Better Survival in Well-Differentiated Endocrine Carcinomas

Abstract

The majority of gastroenteropancreatic well-differentiated endocrine carcinomas (WDEC) express somatostatin receptors (SSTR). To correlate the expression of SSTR subtypes by reverse transcriptase-polymerase chain reaction (RT-PCR) with clinicopathological features and survival in a group of WDEC patients, 42 WDEC tissue specimens from 33 patients were analysed. All patients were treated with somatostatin analogues and had a median follow-up period of 45 months (range 6–196). Neither SSTR2 and SSTR5 expression nor Ki-67 level alone correlated with survival. A significantly better survival rate was observed in patients with tumours expressing SSTR2, SSTR5 and Ki-67 <2%, compared to those with SSTR2– and SSTR5–negative tumours and Ki-67 ≥2% (p < 0.038), with 5-year survival rates of 91 vs. 43%, respectively. Expression of SSTR2 and SSTR5 appears to play a positive prognostic role, possibly correlated with the high affinity that the available somatostatin analogues display for these 2 specific SSTR subtypes.

Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity

“…These findings are unlikely to be related to our SSTR staining score as they were confirmed in binary comparisons of ‘positive' versus ‘negative' tumours. This contrasts with previous reports regarding NETs [11,12,13,14], where SSTR expression was found to be associated with a better prognosis. This is probably related to the heterogeneous spectrum of NETs.…”

“…Both the level of SSTR expression and its prognostic value seem to be related to the degree of tumour differentiation in NETs. Most previous studies have assessed SSTR expression in well-differentiated NETs, which display high and intense expression of SSTR [11,12,13,14]. Corleto et al [13] demonstrated improved survival in patients with well-differentiated NETs who displayed expression of both SSTR2A and 5 in their tumours, together with a low Ki67 proliferative index, but neither SSTR2A nor SSTR5 alone were correlated with survival.…”

“…Expression of SSTR2A and/or SSTR5 has also been associated with improved prognosis in NETs [11,12,13,14] and other cancers [15,16]. …”

Monoclonal Antibodies against the Human Somatostatin Receptor Subtypes 1–5: Development and Immunohistochemical Application in Neuroendocrine Tumors

“…Interestingly, sstr5 positivity was more frequently observed in WD carcinomas (alone or in combination with sstr2a) as compared to WD tumors and was correlated with the presence of angioinvasion and metastasis at diagnosis. Our findings suggest a negative prognostic role of sstr5 in NET and partly contradict the findings of Corleto et al [71] showing that sstr2+/sstr5+ coexpression was associated with a more favorable disease outcome in patients treated with SSAs. However, it needs to be clarified whether the longer survival observed in NET with concomitant sstr2a and sstr5 positivity is of prognostic value per se or if it possibly reflects the high affinity of SSAs for sstr2a and sstr5.…”

“…octreotide and pasireotide primarily showing highest affinity for sstr2a and sstr5, respectively), we investigated the relationship between sstr2a and sstr5 subtype immunoreactivity in NET. We showed that sstr2a and sstr5 were co-stained in 40% of these tumors, in line with the results of Corleto et al [71], who reported a slightly higher coexpression in 57.5% of patients, thus supporting the use of SSAs selectively binding to both of these receptor subtypes in NET. Interestingly, sstr5 positivity was more frequently observed in WD carcinomas (alone or in combination with sstr2a) as compared to WD tumors and was correlated with the presence of angioinvasion and metastasis at diagnosis.…”