Two novel determinants of etoposide resistance in small cell lung cancer.

Patient survival in small cell lung cancer (SCLC) is limited by acquired chemoresistance. Here we report the use of a biologically relevant model to identify novel candidate genes mediating in vivo acquired resistance to etoposide. Candidate genes derived from a cDNA microarray analysis were cloned and transiently overexpressed to evaluate their potential functional roles. We identified two promising genes in the DNA repair enzyme DNA polymerase ß and in the neuroendocrine transcription factor NKX2.2. Specific inhibition of DNA polymerase ß reduced the numbers of cells surviving treatment with etoposide and increased the amount of DNA damage in cells. Conversely, stable overexpression of NKX2.2 increased cell survival in response to etoposide in SCLC cell lines. Consistent with these findings, we found that an absence of nuclear staining for NKX2.2 in SCLC primary tumors was an independent predictor of improved outcomes in chemotherapy-treated patients. Taken together, our findings justify future prospective studies to confirm the roles of these molecules in mediating chemotherapy resistance in SCLC.

Non-small cell lung carcinoma: accuracy of PET/CT in determining the size of T1 and T2 primary tumors.

OBJECTIVE: The purpose of this study was to compare the measurements of primary T1 and T2 non-small cell lung carcinomas (NSCLCs) at PET/CT to determine which modality has the more accurate correlation with the histologic findings. MATERIALS AND METHODS: A retrospective study was performed with the images of 59 patients who underwent surgical resection of T1 and T2 NSCLC and preoperative PET/CT. The maximum measurement of the primary lung tumor was recorded on the PET and unenhanced CT (soft-tissue and lung windows) scans in the largest plane and compared with the maximum dimensions of the histologic specimen. RESULTS: PET and CT measurements both had high concordance with the histologic measurements. CT soft-tissue window measurements had the highest concordance with histologic measurements, but PET had a smaller SD. The greatest linear correlation was between CT soft-tissue and CT lung window measurements, indicating they can be used interchangeably. Outliers were found in both the PET (four tumors) and the two CT (five tumors) groups owing to low (18)F-FDG uptake due to tumor type and surrounding consolidation, respectively. CONCLUSION: PET is better for delineating primary NSCLC if surrounding collapse or consolidation is present. Otherwise, CT with either soft-tissue or lung windows is accurate. Owing to low FDG accumulation, CT is more accurate for assessment of alveolar cell carcinoma.

Cystic primary pulmonary synovial sarcoma presenting as recurrent pneumothorax: report of 4 cases.

Pleuropulmonary synovial sarcoma is a rare malignancy that often presents like any other thoracic tumor with symptoms such as chest pain or cough. Here we describe 4 young adults who underwent surgery for apparently benign recurrent pneumothoraces and who, unexpectedly, were found upon histologic and molecular examination of the resection specimen to have cystic primary pleuropulmonary synovial sarcoma. These cases highlight (a) the importance of cytogenetic analysis in making the diagnosis, as confusion with other spindle cell sarcomas or cystic neoplasms can occur and (b) the importance of thorough examination of all resected tissue in cases of recurrent pneumothorax.

Tissue banking of diagnostic lung cancer biopsies for extraction of high quality RNA.

INTRODUCTION: There is a clear need to develop a practical approach to obtain high quality RNA for gene expression analysis from lung cancer patients. Current approaches are restricted to using material from surgical resection specimens. We systematically investigated whether high quality RNA could be obtained from routine lung cancer diagnostic biopsies to determine the optimum method. METHODS: Extra biopsies were taken at diagnosis from patients later confirmed to have lung cancer. Comparisons were made between RNA extracted from samples snap frozen in liquid nitrogen and those treated with an RNA preservative before freezing. Further comparisons were made between biopsies taken by different methods. RESULTS: Acceptable RNA for gene expression analysis was extracted from 72% of lung cancer biopsies. Use of an RNA preservative for storage allowed the extraction of higher quality, more intact RNA from biopsies gathered by both endobronchial forceps and transbronchial needle aspiration. High quality RNA could also be extracted from computed tomography-guided needle core biopsies. CONCLUSION: Banking lung cancer biopsy specimens by storage in an RNA preservative solution will allow use of a broader spectrum of lung cancers for gene expression analysis. We describe a model that makes personalized medicine for lung cancer patients a more practical proposition.