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We investigated the oncogenic role of SETDB1, focusing on non-small cell lung cancer (NSCLC), which has high expression of this protein. A total of 387 lung cancer cases were examined by immunohistochemistry; 72% of NSCLC samples were positive for SETDB1 staining, compared to 46% samples of normal bronchial epithelium (106 cases) (p <0.0001). The percentage of positive cells and the intensity of staining increased significantly with increased grade of disease. Forced expression of SETDB1 in NSCLC cell lines enhanced their clonogenic growth in vitro and markedly increased tumour size in a murine xenograft model, while silencing (shRNA) SETDB1 in NSCLC cells slowed their proliferation. SETDB1 positively stimulated activity of the WNT-β-catenin pathway and diminished P53 expression, resulting in enhanced NSCLC growth in vitro and in vivo. Our finding suggests that therapeutic targeting of SETDB1 may benefit patients whose tumours express high levels of SETDB1., (Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Background: SOX7 is a transcription factor belonging to the SOX family. Its role in lung cancer is unknown., Methods: In this study, whole genomic copy number analysis was performed on a series of non-small cell lung cancer (NSCLC) cell lines and samples from individuals with epidermal growth factor receptor (EGFR) mutations using a SNP-Chip platform. SOX7 was measured in NSCLC samples and cell lines, and forced expressed in one of these lines., Results: A notable surprise was that the numerous copy number (CN) changes observed in samples of Asian, non-smoking EGFR mutant NSCLC were nearly the same as those CN alterations seen in a large collection of NSCLC from The Cancer Genome Atlas which is presumably composed of predominantly Caucasians who often smoked. However, four regions had CN changes fairly unique to the Asian EGFR mutant group. We also examined CN changes in NSCLC lines. The SOX7 gene was homozygously deleted in one (HCC2935) of 10 NSCLC cell lines and heterozygously deleted in two other NSCLC lines. Expression of SOX7 was significantly downregulated in NSCLC cell lines (8/10, 80%) and a large collection of NSCLC samples compared to matched normal lung (57/62, 92%, p= 0.0006). Forced-expression of SOX7 in NSCLC cell lines markedly reduced their cell growth and enhanced their apoptosis., Conclusion: These data suggest that SOX7 is a novel tumor suppressor gene silenced in the majority of NSCLC samples.

Purpose: Differential diagnosis of small nodules in the lung periphery detected by low-dose chest CT screening is important before surgery. The aim of the study was to discriminate between benign and malignant lesions, identified in our preoperative imaging work-up examinations and confirmed during surgery, for nodules detected on CT screening., Materials and Methods: This study is based on 106 patients (46 men and 60 women, median age: 61.5 years) with 123 CT screening-detected and histologically confirmed nodules smaller than 30 mm in the lung periphery identified between 2002 and 2005 at Azumi General Hospital, Japan. Lesions were classified into three groups according to histological findings: adenocarcinoma, atypical adenomatous hyperplasia (AAH) and inflammatory focal lesions. We examined the visceral pleura during surgery at a location close to lung nodules., Results: The median diameter of resected lung nodules on high-resolution CT (HRCT) was 9.0 mm. Nodules were nonsolid in 42, partly solid in 51 and solid in 30. Histopathological diagnosis was lung cancer in 69, AAH in 21, other noninflammatory tumours in 6 and inflammatory lesions in 27. Fifty-four lesions were located in the subpleural zone. Eight of 123 nodules showed local pleural adhesions (LPA), while 2 were buried in extensive pleural adhesion. LPA was noted more frequently in inflammatory nodules than in cancer nodules (P<.01)., Conclusion: The presence of LPA in close proximity to a small nodule is indicative of noncancerous lesion. This feature allows the discrimination of pulmonary peripheral inflammatory lesion from peripheral small cancer on chest low-dose CT screening.

An 82-year-old woman, a never smoker, had a radical operation for CT screening revealed lung cancer in an other hospital in 1997. She was admitted to our hospital complaining of dry cough and dyspnea on effort in March 2004. She was diagnosed to have a local recurrence of lung cancer 6 years after the operation. After she underwent radiotherapy of the mediastinum (total 60 Gy) and daily administration of gefitinib for two weeks, the administration of gefitinib was continued every other day in the outpatient clinic. During follow-up, CYFRA gradually increased to 3.8 ng/mL, but then decreased to the normal range. The tumor response rate of metastasized lymph nodes of bronchial bifurcation reached 36%, and it was confirmed to be a partial response. Without harmful phenomena except skin eruptions, her quality of life was good with a performance status (PS) 0 at 85 years 4 months of age, 9 years 2 months after the resection, with 2 years 5 months of gefitinib administration. It will be useful as a treatment option for octogenarians having postoperative recurrent lung cancers with every other day administration of gefitinib.

A 47-year-old man was admitted to Shinshu University Hospital in 1992 because of cough and chest abnormal shadow. In 1987, he had an operation for Meibomian gland carcinoma of his right lower eyelid, and also received radiotherapy. His chest X-ray film on admission showed tumor shadows in the bilateral upper lung fields. The chest CT scan showed tumors in the right S1 and the left S3. Bronchofiberscopic findings demonstrated stenosis of the right upper bronchus and an endobronchial mass occluding the left B3. A biopsy specimen of the endobronchial mass revealed sebaceous carcinoma, which was identical with that of the resected eyelid tumor. He received two courses of chemotherapy in a combination of CDDP 75 mg/m2 and ADM 50 mg/m2. The tumors on chest X-ray and CT scan became small by the chemotherapy. Bronchofiberscopy after the chemotherapy also revealed that the stenosis of the right upper bronchus improved and the endobronchial mass in the left B3 had disappeared. He died 8 months after initial chemotherapy with a response duration of 7 months.