Clinical and pathological analysis of 19 cases of medullary thyroid carcinoma without an increase in calcitonin.

BACKGROUND: Medullary thyroid carcinoma (MTC), defined as a malignant tumour with C-cell differentiation, is of neuroendocrine origin and is characterized by the synthesis and secretion of calcitonin (CT). MTC without CT secretion has been reported on rare occasions. The purpose of this study was to evaluate the histological, immunohistochemical, and molecular pathologic features as well as the clinical significance of non-secretory MTC (NCR-MTC). METHODS: A retrospective analysis of patients with NCR-MTC was performed. The clinical features of NCR-MTC, including age, gender, tumour size and number, clinical signs of hypocalcaemia and diarrhoea, and the presence of lymph node metastasis, as well as the pathologic features of the disease, including tumour morphology, presence of neuroendocrine structures, capsular invasion, and immunohistochemical expression and presence of mutations in the RET gene, were evaluated. RESULTS: Nineteen patients with NCR-MTC were identified among 158 patients with MTC, resulting in a prevalence rate of 12.02%. Patients with NCR-MTC typically had masses less than 1cm in size (73.7%, 14/19). Hypocalcaemia was not present in 94.7% (18/19) of patients. While 42.1% (8/19) of patients with NCR-MTC did not have amyloid deposits, only 18% (25/139) of patients with secretory MTC did not have such deposits. While 95.7% (133/139) of the control group of patients with secretory MTC had neuroendocrine tumour structure, only 84.2% (16/19) of the patients with NCR-MTC had this type of tumour structure. Patients with NCR-MTC were also less likely to have vascular tumour thrombus, lymph node metastasis or thyroid capsular invasion. With regard to immunohistochemistry, CT expression was mostly negative, and carcinoembryonic antigen (CEA) expression was positive in 21.1% (4/19) of patients with NCR-MTC, while only 5.8% (8/139) of patients in the control group had positive CEA expression. CONCLUSIONS: The prevalence of NCR-MTC was low (12.02%). This type of tumour was smaller in size and more differentiated. Compared with the control group, relatively few patients had obvious symptoms, hypocalcaemia, lymph node metastasis, thyroid capsular or vascular invasion, or tumours with amyloid or neuroendocrine tumour structure.

miR-200c enhances sensitivity of drug-resistant non-small cell lung cancer to gefitinib by suppression of PI3K/Akt signaling pathway and inhibites cell migration via targeting ZEB1.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. We explored the role of miR-200c in modulating the sensitivity of gefitinib-resistant NSCLC cells and examined the underlying mechanism. The gefitinib-resistant cell line PC-9-ZD and its parental PC-9 cells were used. Growth inhibition was detected by MTT assay. The cell apoptosis was detected by Annexin V/PI assay. Cell migration was assessed by wound-healing assay. RT-PCR was used to detected levels of miR-200c and ZEB1. The PI3k, Bcl-2, Bax, caspase-3 and ZEB1 protein expression were detected using Western blot analysis, and TUNEL, Immunohistochemistry for xenograft model. PC-9-ZD cells had low level of miR-200c expression compared to its parental PC-9 cells. PC-9-ZD cells with miR-200c transfection were more sensitive to gefitinib treatment. Apoptosis induced by gefitinib was observed in PC-9-ZD cells with miR-200c transfection significantly. The levels of phosphorylated-Akt and Bcl-2 expression decreased and levels of Bax and Caspase-3 expression increased in PC-9-ZD cells with miR-200c transfection. Cell migration was inhibited and ZEB1 mRNA level and protein expression were significantly decreased in PC-9-ZD cells with miR-200c transfection. Further in gefitinib resistant xenograft model, miR-200c enhanced sensitivity of gefitinib and induced apoptosis significantly through PI3K/Akt signaling pathway and targeting ZEB1. These results provided insights into the functions of miR-200c and offered an alternate approach in treating gefitinib-resistance NSCLC.