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Objective: To investigate the clinicopathological features and differential diagnosis of NTRK3 gene rearrangement thyroid papillary carcinoma (PTC). Methods: The PTC cases without BRAF V600E mutation were collected at Fujian Provincial Hospital South Branch from January 2015 to January 2020. The cases of NTRK3 gene rearrangement PTC were examined using immunohistochemistry and fluorescence in situ hybridization (FISH). The clinical data, histopathological characteristics, immunohistochemical features and molecular pathological changes were retrospectively analyzed. Data from the TCGA PTC dataset and the literature were also studied. Results: A total of 3 PTC cases harboring NTRK3 gene rearrangement were confirmed. All the patients were female, aged from 26,49,34 years. Histologically, two of them demonstrated a multinodular growth pattern. Only one case showed prominent follicular growth pattern; the other two tumors showed a mixture of follicular, papillary and solid growth patterns. All tumors showed a typical PTC nuclear manifestation, with some nuclear pleomorphism, vacuolated foci and oncocytic features. The characteristic formation of glomeruloid follicular foci was present in two cases which also showed psammoma bodies, and tumoral capsular or angiolymphatic invasion. The background thyroid parenchyma showed chronic lymphocytic thyroiditis. Mitotic rates were low, and no cases had any tumor necrosis. The pan-TRK and TTF1 testing was both positive in 3 cases, while S-100 and mammaglobin were both negative in them. FISH studies confirmed the NTRK3 gene rearrangement in all 3 cases. Studies on the TCGA datasets and literature revealed similar findings. Conclusions: NTRK3 gene rearrangement PTC is rare. It may be easily misdiagnosed due to the lack of histological and clinicopathological characteristics. Molecular studies such as pan-TRK immunostaining, FISH and even next-generation sequencing are needed to confirm the diagnosis. Immunohistochemistry of pan-TRK performed in the PTC cases without BRAF V600E mutation can be used as a good rapid-screening tool. With the emergence of pan-cancer tyrosine receptor kinase inhibitors, proper diagnosis of these tumors can help determine appropriate treatments and improve their outcomes.
Asunto(s)
Femenino , Humanos , Biomarcadores de Tumor , Reordenamiento Génico , Hibridación Fluorescente in Situ , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Receptor trkC , Estudios Retrospectivos , Cáncer Papilar Tiroideo/genética , Neoplasias de la Tiroides/genéticaRESUMEN
Objective To investigate the expression of interleukin-1 β(IL-1 β) and apoptosis in the hippocampus of rats with prolonged febrile seizures(PFS),and to provide the theoretical basis for exploring the brain damage of PFS and the effective prevention and control measures.Methods Ninety-six 14-day-old Sprague-Dawley rats were randomly divided into 3 groups:normal control group(NC group,n =32),hyperthermia group(HC group,n =32) and PFS group(n =32).Lipopolysaccharide combined low-dose Kainic acid of intraperitoneal injection were used to induce PFS.Then the histopathologic changes in hippocampus were viewed by HE staining and electronmicroscope,the expression of IL-1β protein in hippocampus of rats was detected with immunohistochemistry methods,the neuron apoptosis was observed by TdT-mediated dUTP nick end labeling,and the relationship of both was researched.Results 1.Thirty-two rats all appeared seizures in PFS group,the average rectal temperature was (39.3 ± 0.4) ℃ ; while the rats in other groups were not convulsions.2.The TUNEL positive cells in hippocampus CA1 of PFS group were more than that of NC group and HC group at 6 h after the PFS(all P <0.01),reached its highest level at 24 h.3.Measured by immunohistochemistry,the level of IL-1β in the hippocampus of PFS group was significantly higher than that of the NC group and HC group at 6 h after the PFS(all P < 0.01).There was a positive correlation between the expression of IL-1 β and the apoptotic index in hippocampus(r =0.789,P < 0.01).Conclusions IL-1 β expression in the hippocampus increases following PFS in rats,and the increased IL-1 β expression was correlated with neurocyte apoptosis.
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<p><b>OBJECTIVE</b>To explore the effect of Ang-2 on angiogenesis in gastric cancer.</p><p><b>METHODS</b>The expression of Ang-2 mRNA was analyzed by RT-PCR and the expression of VEGF and CD34 was detected by immunohistochemistry in 36 cases of gastric cancer tissues and their paired adjacent gastric mucosa.</p><p><b>RESULTS</b>The expression of Ang-2 mRNA was found both in gastric cancer and their paired adjacent gastric mucosa; the correlationship between the general expression levels of Ang-2 mRNA and microvessel density (MVD) in gastric cancer tissues was not found. However, in 27 cases whose Ang-2 mRNA expression levels in cancer tissues were lower than those in adjacent gastric mucosa. A significant positive correlation between the expression level of Ang-2 mRNA and MVD in the tumor tissues was found (r = 0.411, P < 0.05). In these 27 cases, the MVD in the gastric cancer tissues with positive VEGF expression (45.45 +/- 10.30) was higher than that with negative VEGF expression (30.15 +/- 8.69, P < 0.05), whereas in the other 9 cases whose expression levels of Ang-2 mRNA in cancer tissues were higher than those in adjacent gastric mucosa, a significant negative correlation between expression level of Ang-2 mRNA and MVD in the tumor tissues (r = -0.758, P < 0.05), but without correlation between the MVD and VEGF.</p><p><b>CONCLUSION</b>Under the conditions that the expression of Ang-2 mRNA in cancer tissues was lower than that in adjacent gastric mucosa, VEGF could promote the sprouting of new vessels along with Ang-2 upregulation. But under the conditions that the expression of Ang-2 mRNA in cancer tissues was higher than that in adjacent gastric mucosa, Ang-2 inhibited angiogenesis. Angiopoietin-2 may play a dual effect on angiogenesis in gastric cancer.</p>