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.

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 b and in the neuroendocrine transcription factor NKX2.2. Specific inhibition of DNA polymerase b 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. Cancer Res; 71(14); 4877-87. Ó2011 AACR.

Introduction:Survival in small cell lung cancer (SCLC) is limited by the development of chemoresistance. Factors associated with chemoresistance in vitro have been difficult to validate in vivo. Both Bcl-2 and β1-integrin have been identified as in vitro chemoresistance factors in SCLC but their importance in patients remains uncertain. Tissue microarrays (TMAs) are useful to validate biomarkers but no large TMA exists for SCLC. We designed an SCLC TMA to study potential biomarkers of prognosis and then used it to clarify the role of both Bcl-2 and β1-integrin in SCLC.Methods:A TMA was constructed consisting of 184 cases of SCLC and stained for expression of Bcl-2 and β1-integrin. The slides were scored and the role of the proteins in survival was determined using Cox regression analysis. A meta-analysis of the role of Bcl-2 expression in SCLC prognosis was performed based on published results.Results:Both proteins were expressed at high levels in the SCLC cases. For Bcl-2 (n=140), the hazard ratio for death if the staining was weak in intensity was 0.55 (0.33–0.94, P=0.03) and for β1-integrin (n=151) was 0.60 (0.39–0.92, P=0.02). The meta-analysis showed an overall hazard ratio for low expression of Bcl-2 of 0.91(0.74–1.09).Conclusions:Both Bcl-2 and β1-integrin are independent prognostic factors in SCLC in this cohort although further validation is required to confirm their importance. A TMA of SCLC cases is feasible but challenging and an important tool for biomarker validation.