We report the case of a 58-year-old male presenting with giant cell myocarditis and myositis associated with thymoma following treatment with carboplatin and paclitaxel. The patient was diagnosed as having stage IVa thymoma. Acetylcholine receptor binding antibody titers were positive at 42 nmol/l, although the patient exhibited no symptoms of myasthenia gravis (MG). The patient was treated with a combination of carboplatin and paclitaxel. However, 18 days following administration of this second cycle of chemotherapy, the patient developed a low-grade fever. Twenty-one days after receiving the second cycle of chemotherapy, the patient was admitted to the Nagoya City University Medical School complaining of general fatigue. Serum levels of creatinine phosphokinase (7,271 U/l), alanine aminotransferase (469 U/l) and aspartate aminotransferase (561 U/l) were elevated. Electromyography revealed no evidence of a neuromuscular junction defect or myopathic process. The patient developed progressive muscle weakness and succumbed to the disease in hospital on day 9. An autopsy revealed thymoma invasion of the left parietal and visceral pleura, pericardium and diaphragm. Numerous skeletal muscle groups and myocardium exhibited diffuse lymphocytic infiltration. Although it has been suggested that myocardial disorders may occur in patients with thymoma and/or MG, the mechanism involved remains unknown. This second report may provide new data regarding giant cell myocarditis and myositis associated with thymoma following treatment with carboplatin and paclitaxel.

Large tumor suppressor (LATS) 1 and 2 are tumor suppressor genes implicated in the regulation of the cell cycle. The methylation statuses of the promoter regions of these genes were studied in Japanese lung cancers. The methylation statuses of the promoter regions of LATS1 and LATS2 were investigated by methylation-specific PCR. The findings were compared to clinicopathological features of lung cancer. Methylation-specific PCR showed that the LATS1 promoter region was hypermethylated in 95 out of 119 (79.8%) lung cancers. The methylation status of LATS1 was significantly associated with squamous histology (p=0.0267) and smoking status (never smoker vs. smoker; p=0.0399). LATS1-ummethylated patients harbored more EGFR mutations (p=0.0143). The LATS2 promoter region was hypermethylated in 160 out of 203 (78.8%) lung cancers. However, the methylation status had no association with the clinicopathological characteristics of the lung cancers cases. Both the LATS1 and LATS2 methylation statuses did not correlate with survival of lung cancer patients. Thus, the EGFR methylation status of the LATS genes has limited value in Japanese lung cancers.

The incidence of chromosome 3p gene alterations is one of the most frequent and earliest documented events in lung cancer. This study aimed to investigate promoter methylation in the deleted in lung and esophageal cancer 1 (DLEC1) gene, as well as the p16 and CDH1 genes in Japanese lung cancer cases. The methylation status of the promoter regions of DLEC1, p16 and CDH1 was investigated using methylation-specific PCR. The findings were compared to the clinicopathological features of lung cancer. Methylation-specific PCR showed that the DLEC1 promoter region was methylated in 65 out of 116 (56%) lung cancers. Patients with DLEC1-methylated cancer were associated with a significantly worse prognosis than those with unmethylated cancer (p=0.0368; hazard ratio=1.83). The p16 methylation status correlated with squamous histology (p=0.03) and smoking status (never smoker vs. smoker; p=0.0122). Patients with p16 ummethylated cancer harbored more EGFR mutations (p=0.0071). The CDH1 promoter region was hypermethylated in 65 out of 118 (55.1%) lung cancer cases. However, the CDH1 methylation status was not associated with the clinicopathological characteristics of the lung cancer types. p16 and CDH1 methylation status did not correlate with survival in the lung cancer patients. Thus, in our Japanese cohort, the methylation status of the DLEC1 gene was a marker of poor prognosis independent of stage.