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Endocrine Abstracts (2023) 90 RC9.6 | DOI: 10.1530/endoabs.90.RC9.6

1National Center for Global Health and Medicine, Department of Diabetes, Endocrinology and Metabolism, Shinjuku-ku, Tokyo, Japan; 2National Cancer Center Hospital, Department of Diagnostic Pathology, Japan; 3National Cancer Center Hospital, Department of Medical Oncology, Japan; 4Tohoku University Graduate School of Medicine, Department of Pathology, Japan; 5National Center for Global Health and Medicine, Department of Breast and Medical Oncology, Japan


Introduction: Pheochromocytoma and paraganglioma (PPGL) are rare endocrine tumors with few effective treatment options for malignant cases. Novel therapeutic indications, such as 177Lu-DOTA-TATE and immune checkpoint inhibitors (ICIs) for patients with PPGL, have been investigated in several clinical trials. Emerging evidence shows that somatostatin receptor 2 (SSTR2) in other cancer types correlates with the tumor microenvironment (TME) activation and could be a predictive biomarker of ICIs as well as 177Lu-DOTA-TATE. Among gastroenteropancreatic neuroendocrine tumors, SSTR2 expression is associated with a low-grade tumor. However, the association between the expression of SSTR2 and TME and clinical features in PPGL has not yet been reported.

Methods: We studied the immunohistochemical expression of SSTR2A and the immune cells, including tumor infiltrating lymphocytes (CD4 and CD8), tumor associated macrophages (CD68 and CD163), and angiogenic markers (CD31 and intratumoral hemorrhage areas) using specific antibodies on archived formalin-fixed, paraffin-embedded tissue of tumor samples in 53 patients with PPGL diagnosed between 1988 and 2020 in two national center hospitals in Japan. We compared those data with clinical and histopathological factors.

Results: The cohort consisted of 23 (43.4%) patients with pheochromocytoma and 30 (56.6%) patients with paraganglioma, including 27 aggressive tumors (metastasis or local invasion) and 29 functional PPGLs with a mean follow-up duration of 81.1±82.6 months. The median age was 46 (range, 17-80), and 62.3% of the patients were female. The expression of SSTR2A was strongly increased in 19 samples (35.8%). The positive staining score for SSTR2A was significantly more frequently associated with aggressive tumors (78.9% vs 35.3%, P=0.004), high Ki-67 index (5.15 [1.6 – 29.6] vs 2.35 [0.2 – 46.9], P=0.001), high GAPP score (6.40±1.80 vs 4.84±1.97, P=0.013), and high PASS score (9.33±3.52 vs 6.94±3.35, P=0.029) compared to the negative staining score for SSTR2A. No correlation was found between the staining score for SSTR2A expression and other factors: functional status, primary tumor sites, tumor size, intratumoral hemorrhage areas, and the positive cells of CD4, CD8, CD31, CD68, and CD163.

Conclusion: SSTR2A could be a predictive marker of more aggressive PPGL and would play an essential role in further clinical investigations in patients with PPGL. Whereas, since SSTR2A was expressed independently of clinical features and TME status, immunohistochemical analysis of SSTR2A for each tumor should be performed for treatment selection.

Volume 90

25th European Congress of Endocrinology

Istanbul, Turkey
13 May 2023 - 16 May 2023

European Society of Endocrinology 

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