Background. Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective in patients with nonsmall cell lung cancer with epidermal growth factor receptor (EGFR) mutation, EGFR-TKIs have a risk of inducing fatal interstitial lung disease (ILD). The selection of chemotherapy based on the EGFR mutation status is recommended, however, the frequency of EGFR mutation in patients with ILD and the efficacy and safety of EGFR-TKI in patients with ILD and EGFR mutation are unknown. Methods. We retrospectively reviewed the association of the EGFR mutation status of nonsmall cell lung cancer and pulmonary diseases. Based on high-resolution computed tomography (HRCT) performed at diagnosis of lung cancer, patients were categorized into three groups: normal, emphysema, and fibrosis. Results. Of 198 patients with nonsmall cell lung cancer, we identified 52 (26.3%) patients with an EGFR mutation. EGFR mutations were identified in 43 (35.2%) of 122 patients with normal lungs, 8 (13.6%) of 59 with emphysema, and 1 (5.9%) of 17 with pulmonary fibrosis. Of the 52 patients with EGFR mutation, 43 patients received gefitinib. One patient with an EGFR mutation and fibrosis developed fatal ILD. There was not a significant difference in median overall survival from gefitinib treatment between never-smokers and smokers (797 days versus not reached; P = 0.96). Conclusions. Patients with sensitive EGFR mutation and normal lungs may benefit from an EGFR-TKI treatment even if they have smoking history.

We report a case of a gastrointestinal stromal tumor (GIST) of the stomach that demonstrated a stepwise progression from low- to high-grade malignancy. The patient had been followed for a small gastric submucosal tumor that had turned malignant after 8 years of indolence, manifested by tarry stools. The tumor was enucleated, and gastric GIST was diagnosed. The most significant histological finding was that the tumor comprised two clearly demarcated areas, one with less aggressive characteristics and the other with highly aggressive characteristics. The patient exhibited multiple liver metastases 24 months after surgery. Imatinib mesylate was not administered throughout the clinical course because it was not available for clinical use at that time. The patient followed an unfavorable clinical course and died of liver dysfunction 55 months after surgery. Autopsy was performed. By comparing the immunohistochemical profiles of primary and metastatic tumors, it was established that only the tumor cells with highly aggressive characteristics had metastasized.

IntroductionNon-small-cell lung cancer harboring an activated epidermal growth factor receptor mutation exhibits a good response to epidermal growth factor receptor-tyrosine kinase inhibitors; however, clinicians often experience treatment failure following the development of resistance to epidermal growth factor receptor-tyrosine kinase inhibitor.Case presentationWe here report a case of a 56-year-old Japanese woman with non-small-cell lung carcinoma with a secondary T790M mutation associated with resistance to epidermal growth factor receptor-tyrosine kinase inhibitor that maintained sensitivity of brain metastases to epidermal growth factor receptor-tyrosine kinase inhibitor. An autopsy showed that the primary focus had a T790M mutation; however, no mutations of T790M were found in the brain metastases.ConclusionThis case demonstrates the detection of T790M was associated with the clinical responsiveness to epidermal growth factor receptor-tyrosine kinase inhibitor.

Amyloidosis in non-Hodgkin's lymphoma (NHL) is known to be of the AL type, and AA-type amyloidosis in NHL is extremely rare. Herein is reported an autopsy case of follicular lymphoma that transformed to diffuse large B-cell lymphoma (DLBCL) in a relapse associated with systemic AA amyloidosis. CMV infection in an immunocompromised state with chemotherapy against DLBCL may have been involved in amyloid accumulation. The serum amyloid A (SAA)1 gene polymorphism, SAA1.2/1.3, might have also been another factor in this case, considering the risk of AA amyloidosis in Japanese patients with rheumatoid arthritis.

Aim/Background: Functional inactivation of BRCA1 gene increase the risk of developing breast cancer. Germline mutation of BRCA1 is responsible for Hereditary Breast and Ovarian Cancer. BRCA1 promoter methylation has been proposed as an alternative mechanism to inactivate BRCA1 in sporadic breast cancer. Most of cases with BRCA1 mutations are triple negative breast cancer (TNBC) but, the association between each subtypes of breast cancer and BRCA1 methylation is not clear. Thus, we investigated the BRCA1 methylation status and protein expression of BRCA1 in each subtypes of breast cancer.Methods: 121 samples, which contained 82 frozen and 39 acetone embedded samples, were obtained from breast cancer patients undergoing surgery with informed consents. Using methylation-specific PCR analysis which was validated based on cell line survey, methylation levels were calculated as a percentage of the reference. Setting a cut-off value of 10%, positive methylation was determined. The association between BRCA methylation and clinicopatholgical factors was analyzed by Chi-square test. Results: The number of each subtypes is 43 in hormone receptor (HR) + , HER2-, 21 in HR + , HER2-, 19 in HR-, HER2 + , 38 in TNBC. Positive methylation was detected only in triple negative breast cancer (9/38, 24%) which is statistically significant compared with HR + , HER2-(0/43, p < 0.0.1), HR + , HER2 + (0/21, p < 0.05), and HR-, HER2-(0/19, p < 0.05). In cases with BRCA methylation, six out of eight cancer (75%) showed absence of BRCA protein. Frequency of low expression of BRCA protein by subtypes is; TNBCs (12/31, 39%), HR + , HER2-(2/41, 4.9%), HR + , HER2-(0/21, 0%), HR-, HER2+ (1/10, 10%) ( p < 0.01). Conclusions: Our data suggest hypermethylation of BRCA1 is highly related with TNBC subtype, which decrease BRCA protein expression. PARP inhibitors might be used as therapeutic targets for these population. Disclosure: All authors have declared no conflicts of interest.