Metastatic Pheochromocytoma and Paraganglioma: Somatostatin Receptor 2 Expression, Genetics, and Therapeutic Responses

被引：32

作者：

Fischer, Alessa ^{[1
,2
]}

Kloos, Simon ^{[1
,2
]}

Maccio, Umberto ^{[3
]}

Friemel, Juliane ^{[3
]}

Remde, Hanna ^{[4
]}

Fassnacht, Martin ^{[4
]}

Pamporaki, Christina ^{[5
]}

Eisenhofer, Graeme ^{[5
]}

Timmers, Henri J. L. M. ^{[6
]}

Robledo, Mercedes ^{[7
,8
]}

Fliedner, Stephanie M. J. ^{[9
]}

Wang, Katharina ^{[10
]}

Maurer, Julian ^{[10
]}

Reul, Astrid ^{[1
,2
]}

Zitzmann, Kathrin ^{[10
]}

Bechmann, Nicole ^{[11
]}

Zygiene, Gintare ^{[11
]}

Richter, Susan ^{[11
]}

Hantel, Constanze ^{[1
,2
,5
]}

Vetter, Diana ^{[12
]}

Lehmann, Kuno ^{[12
]}

Mohr, Hermine ^{[13
]}

Pellegata, Natalia S. ^{[13
,14
]}

Ullrich, Martin ^{[15
]}

Pietzsch, Jens ^{[15
,16
]}

Ziegler, Christian G. ^{[4
,5
]}

Bornstein, Stefan R. ^{[1
,2
,5
]}

Kroiss, Matthias ^{[10
]}

Reincke, Martin ^{[10
]}

Pacak, Karel ^{[17
]}

Grossman, Ashley B. ^{[18
,19
]}

Beuschlein, Felix ^{[1
,2
,10
]}

Noelting, Svenja ^{[1
,2
,10
]}

机构：

[1] Univ Zurich UZH, Dept Endocrinol Diabetol & Clin Nutr, Ramistr 100, CH-8091 Zurich, Switzerland

[2] Univ Zurich UZH, CH-8091 Zurich, Switzerland

[3] Univ Hosp Zurich, Dept Pathol & Mol Pathol, CH-8091 Zurich, Switzerland

[4] Univ Wurzburg, Univ Hosp, Dept Internal Med 1, Div Endocrinol & Diabet, D-97080 Wurzburg, Germany

[5] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Internal Med 3, D-01307 Dresden, Germany

[6] Radboud Univ Nijmegen, Dept Internal Med, Div Endocrinol, Med Ctr, NL-6525 GA Nijmegen, Netherlands

[7] Spanish Natl Canc Res Ctr CNIO, Hereditary Endocrine Canc Grp, Madrid, Spain

[8] Ctr Invest Biomed Red Enfermedades Raras, Madrid, Spain

[9] Univ Med Ctr Schleswig Holstein, Dept Med 1, D-23538 Lubeck, Germany

[10] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Med 4, D-80336 Munich, Germany

[11] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Inst Clin Chem & Lab Med, Med Fac Carl Gustav Carus, Fetscherstr, D-01307 Dresden, Germany

[12] Univ Hosp, Dept Visceral & Transplantat Surg, CH-8091 Zurich, Switzerland

[13] Helmholtz Zentrum Munchen, Inst Diabet & Canc, D-85764 Neuherberg, Germany

[14] Univ Pavia, Dept Biol & Biotechnol, I-27100 Pavia, Italy

[15] Helmholtz Zentrum Dresden Rossendorf HZDR, Inst Radiopharmaceut Canc Res, Dept Radiopharmaceut & Chem Biol, Dresden, Germany

[16] Tech Univ Dresden, Fac Chem & Food Chem, Sch Sci, Dresden, Germany

[17] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, NIH, Rockville, MD 20847 USA

[18] Univ Oxford, Green Templeton Coll, Oxford, England

[19] Royal Free Hosp, ENETS Ctr Excellence, NET Unit, London, England

来源：

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM | 2023年 / 108卷 / 10期

关键词：

metastatic pheochromocytoma; paraganglioma; SDHB mutation; SDHx mutation; somatostatin receptor 2; somatostatin receptor-based therapies; PRRT; RADIONUCLIDE THERAPY; ADRENAL-TUMORS; LU-177-DOTATATE; NECK; IMMUNOHISTOCHEMISTRY; LOCALIZATION; OCTREOTIDE; MANAGEMENT; CONSENSUS; SURVIVAL;

D O I：

10.1210/clinem/dgad166

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Context Pheochromocytomas and paragangliomas (PPGLs) with pathogenic mutations in the succinate dehydrogenase subunit B (SDHB) are associated with a high metastatic risk. Somatostatin receptor 2 (SSTR2)-dependent imaging is the most sensitive imaging modality for SDHB-related PPGLs, suggesting that SSTR2 expression is a significant cell surface therapeutic biomarker of such tumors. Objective Exploration of the relationship between SSTR2 immunoreactivity and SDHB immunoreactivity, mutational status, and clinical behavior of PPGLs. Evaluation of SSTR-based therapies in metastatic PPGLs. Methods Retrospective analysis of a multicenter cohort of PPGLs at 6 specialized Endocrine Tumor Centers in Germany, The Netherlands, and Switzerland. Patients with PPGLs participating in the ENSAT registry were included. Clinical data were extracted from medical records, and immunohistochemistry (IHC) for SDHB and SSTR2 was performed in patients with available tumor tissue. Immunoreactivity of SSTR2 was investigated using Volante scores. The main outcome measure was the association of SSTR2 IHC positivity with genetic and clinical-pathological features of PPGLs. Results Of 202 patients with PPGLs, 50% were SSTR2 positive. SSTR2 positivity was significantly associated with SDHB- and SDHx-related PPGLs, with the strongest SSTR2 staining intensity in SDHB-related PPGLs (P = .01). Moreover, SSTR2 expression was significantly associated with metastatic disease independent of SDHB/SDHx mutation status (P < .001). In metastatic PPGLs, the disease control rate with first-line SSTR-based radionuclide therapy was 67% (n = 22, n = 11 SDHx), and with first-line "cold" somatostatin analogs 100% (n = 6, n = 3 SDHx). Conclusion SSTR2 expression was independently associated with SDHB/SDHx mutations and metastatic disease. We confirm a high disease control rate of somatostatin receptor-based therapies in metastatic PPGLs.

引用

页码：2676 / 2685

页数：10

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