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

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

Diversity of terrestrial tardigrades (Tardigrada) in Lithuania

Tardigrades (Tardigrada) are small water-dwelling invertebrates found almoust everywhere around the world in water and terrestrial habitats, even in Artic and Antartic. In this study diversity and distribution of terrestrial tardigrades (Tardigrada) were investigated in mosses and lichen (X. parietina). Mosses were collected in Kaunas botanical garden, lichens – in Kaunas, Jonava and Kaišiadorys districts from polluted and unpollutes sites. Four species, belonging to genera Ramazzottius, Macrobiotus, Milnesium, Isohypsibius were found in mosses and seven species, belonging to genera Ramazzottius, Macrobiotus, Milnesium, Isohypsibius, Hypsibius were found in lichen (X. parietina). The study results showed that dominant tardigrade species in mosses was Macrobiotus richersi (?), in lichen (polluted and unpolluted sites) most abundant species was Ramazzottius oberhaeuseri. Less dominant, but found in all samples (mosses and lichen) were Macrobiotus hufelandi and Milnesium tardigradumBiologijos katedraVytauto Didžiojo universiteta