Clinicopathologic characteristics of pancreatic neuroendocrine tumors and relation of somatostatin receptor type 2A to outcomes

Okuwaki, Kosuke; Kida, Mitsuhiro; Mikami, Taisei; Yamauchi, Hiroshi; Inoue, Hiroshi; Miyazawa, Shiro; Iwai, Tomohisa; Takezawa, Miyoko; Saegusa, Makoto; Watanabe, Masahiko; Koizumi, Wasaburo

doi:10.1002/cncr.28341

Cited by 63 publications

(69 citation statements)

References 20 publications

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“…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.…”

Section: Discussioncontrasting

confidence: 55%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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. Okuwaki et al [12] found SSTR2A expression to be associated with better prognosis in well-differentiated NETs but not in poorly differentiated neuroendocrine carcinomas. For such tumours, whose behaviour is probably closer to MCCs, SSTR did not influence survival.…”

Section: Discussionmentioning

confidence: 99%

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

Section: Introductionmentioning

confidence: 99%

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

Gardair¹,

Samimi

Touzé

et al. 2015

Neuroendocrinology

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Background/Aims: Merkel cell carcinoma (MCC) is a rare high-grade neuroendocrine tumour of the skin. It has been speculated that MCCs express somatostatin receptors (SSTRs), but this has never been assessed in a large series of MCCs. The main aim of this study was to assess the expression of SSTR2A and SSTR5 in MCC tumours. The secondary aims were to assess whether expression of SSTR was associated with the Ki67 proliferative index, Merkel cell polyomavirus (MCPyV) status, clinical characteristics and outcome. Methods: Clinical data and tumours were collected from an ongoing cohort of French patients with MCC. Immunohistochemistry was performed with anti-SSTR2A and anti-SSTR5 monoclonal antibodies, and tumours were classified into 3 groups: ‘no expression', ‘low expression' and ‘moderate expression' using an SSTR staining score. Results: SSTR expression was assessed for 105 MCC tissue samples from 98 patients, and clinical characteristics were available for 87 of them. SSTR expression was consistent between the primary skin tumour and the corresponding metastases for SSTR2A and SSTR5 in 3/7 and 6/7 cases, respectively. SSTR2A and SSTR5 were expressed in 58 cases (59.2%) and in 44 cases (44.9%), respectively. Overall, at least one SSTR was expressed in 75 tumours (76.5%). SSTR expression was not associated with clinical characteristics, Ki67 proliferative index, recurrence-free survival or MCC-specific survival. Expression of SSTR2A was associated with MCPyV status in MCC tumours but not SSTR5. Conclusion: SSTRs were expressed in a high proportion of MCCs, although expression was heterogeneous between tumours and was not associated with disease severity.

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Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Gardair¹,

Samimi

Touzé

et al. 2015

Neuroendocrinology

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“…Overexpression of vascular endothelial growth factor receptors not only in the endothelial cells or in the stroma but also in the surface of the neuroendocrine cells has been extensively observed [23,24] . The presence of somatostatin receptors over the surface of pNETs tumor cells is over 90% [25,26] . Somatostatin receptors are playing a crucial role not only in the production and release of active peptides by the tumor cells but also in the growth and tumor cell survival process.…”

Section: Overcoming Resistances In Pnets: the Basic Science Perspectivementioning

confidence: 99%

Sequential treatment in disseminated well- and intermediate-differentiated pancreatic neuroendocrine tumors: Common sense or low rationale?

Grande¹

2016

WJCO

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Fortunately, the landscape of the systemic treatment for grade 1 and 2 pancreatic neuroendocrine tumors has changed in the last decade with at least four different alternatives approved in the field. Chemotherapy, somatostatin analogues, sunitinib and everolimus remind valid options according to the most referenced international guidelines. However, and although this is something done in the routine practice, there is a lack of evidence for the use of any of these strategies after failure to the others. Moreover, further sequential alternatives in third or fourth line have never been tested prospectively. The need for a better understanding of the rationale to sequence different systemic options is even greater in non-pancreatic neuroendocrine tumors since available therapies are scarce. Sequential strategies in other solid tumors have led to a clear improvement in overall survival. This is also believed to occur in neuroendocrine tumors but no clear data on it has been delivered yet. We postulate that the different mode of action of the systemic options available for the treatment of neuroendocrine tumors may avoid the complete resistance of one option after the other and that sequential use of these agents will be translated into a longer overall survival of patients. Prospective and randomized trials that seek for the activity of drugs after failure to another systemic alternatives are highly needed in this field of neuroendocrine tumors.

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Algorithmic approach to neuroendocrine tumors in targeted biopsies: Practical applications of immunohistochemical markers

Duan

Mete

2016

Cancer Cytopathology

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Neuroendocrine tumors (NETs) constitute a heterogeneous group of neoplasms with distinct biological behaviors, depending on the site of origin and the degree of tumor proliferation. Although advances in biochemical and radiological modalities have enhanced the ability to detect NETs, tissue diagnosis remains the gold standard to assess tumor characteristics for treatment decision making. In an era with growing demands for precision diagnostics based on smaller tissue samples, immunohistochemistry has become an indispensable tool in the pathologist's repertoire. In conjunction with clinical findings and cytomorphology, complementary use of 1) markers of neuroendocrine differentiation, 2) markers confirming epithelial nature, 3) markers of cellular proliferation, 4) transcription factors and hormonal markers, as well as 5) predictive and prognostic markers may be necessary to guide patient management in NETs. The current review summarizes common applications of these immunohistochemical markers when confronted with a potential neuroendocrine neoplasm, and proposes a stepwise algorithmic approach to avoid diagnostic errors in targeted biopsies. Cancer Cytopathol 2016;124:871-84. V C 2016 American Cancer Society.

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Clinicopathologic characteristics of pancreatic neuroendocrine tumors and relation of somatostatin receptor type 2A to outcomes

Cited by 63 publications

References 20 publications

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

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

Sequential treatment in disseminated well- and intermediate-differentiated pancreatic neuroendocrine tumors: Common sense or low rationale?

Algorithmic approach to neuroendocrine tumors in targeted biopsies: Practical applications of immunohistochemical markers

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