The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort.

BACKGROUND: Many studies on thyroid follicular tumors have reported the presence of somatic mutations to three forms of RAS: HRAS, KRAS, and NRAS. However, the frequency and clinical significance of these RAS mutations remain unclear, in large part due to the different methodologies being used for mutation analysis and the limited number of cases featured in studies. To clarify the significance of RAS mutations, we examined a large number of follicular adenomas and carcinomas obtained from a single institute using established methods for the analysis of RAS. METHODS: Tumor samples from 40 follicular adenoma and 58 follicular carcinoma patients treated at the Kanagawa Cancer Center Hospital were analyzed. The three RAS mutations at codons 12 and 61 were assessed with a polymerase chain reaction-based loop-hybrid mobility shift assay followed by confirmation with direct sequencing. The relationships between mutation status and clinicopathological features at the time of the initial operation and the prognosis of the patients were also analyzed. RESULTS: Twelve out of 40 (30%) adenomas harbored RAS mutations. In contrast, 33 out of 58 (57%) follicular carcinomas harbored RAS mutations, and the mutation was predominantly found in the NRAS codon 61 (22/33, 67%, p<0.01). The rate of gene mutations was significantly higher in the carcinomas than in the adenomas (p<0.01). The NRAS codon 61 mutation in follicular carcinomas was positively associated with distant metastases through the entire clinical course of the patients (p<0.05), and RAS mutations were associated with poor overall patient survival (p<0.05). CONCLUSIONS: We investigated the frequency of RAS mutations in follicular thyroid tumors from a large number of cases obtained from a single institute. The predominance of NRAS codon 61 mutations as a feature of carcinomas indicates that the diagnosis of adenoma alongside the presence of this mutation should be made cautiously. Our study raises the possibility that follicular adenomas with the RAS mutations have an inherent malignant potential; however, the clinical significance of this finding should be further investigated in more patients and over a longer follow-up period.

[Chemotherapy with linezolid for chronic synthetic graft infection].

Infection of thoracic synthetic grafts is a serious problem, potentially leading to septicemia. Total removal of infected grafts might be too invasive for patients in poor general condition or who have long synthetic grafts. Effective and safe chemotherapy regimens are needed to control infection. A 75-year-old man with infected synthetic grafts of the ascending aorta, aortic arch, descending aorta, and thoracoabdominal aorta caused by methicillin-resistant Staphylococcus aureus was admitted to our hospital because of septicemia. He had previously received vancomycin for about 1 year at an outpatient clinic. The blood culture after admission was positive for vancomycin-intermediate Staphylococcus aureus. Linezolid was effective against septicemia, but caused side effects, such as blurred vision, severe diarrhea, and thrombocytopenia. Intermittent oral treatment with linezolid (1,200 mg/day) was then given for 7 days every 2 weeks. This treatment decreased the incidence of the side effects and had a beneficial effect on the infection.