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Rationale: Lung adenocarcinoma histology and clinical outcome are heterogeneous and associated with tumor invasiveness.Objectives: We hypothesized that invasiveness is associated with a distinct molecular signature and that genes differentially expressed in tumor or adjacent stroma will identify cell surface signal transduction and matrix remodeling pathways associated with the acquisition of invasiveness in lung adenocarcinoma.Main Results: Microarray analysis of microdissected noninvasive bronchioloalveolar carcinoma (BAC) and invasive adenocarcinoma and adenocarcinoma-mixed type with BAC features identified transcriptional profiles of lung adenocarcinoma invasiveness. Among the signature set that was lower in adenocarcinoma-mixed compared with BAC was the type II transforming growth factor beta (TGF-beta) receptor, suggesting downregulation of TGFbetaRII is an early event in lung adenocarcinoma metastasis. Immunostaining in independently acquired specimens demonstrated a correlation between TbetaRII expression and length of tumor invasion. Repression of TGFbetaRII in lung cancer cells increased tumor cell invasiveness and activated p38 mitogen-activated protein kinases. Microarray analysis of invasive cells identified potential downstream mediators of TGFbetaRII with differential expression in lung adenocarcinomas.Conclusions: The repression of type II TGF-beta receptor may act as a significant determinant of lung adenocarcinoma invasiveness, an early step in tumor progression toward metastasis. [ABSTRACT FROM AUTHOR]

Background: The risk factors for venous thromboembolism (VTE) following lung transplantation are not well established. We aimed to estimate the incidence of VTE and to identify the risk factors for VTE after lung transplantation., Methods: We performed a nested case-control study within the cohort of 121 patients who underwent lung transplantation at our center between August 2001 and July 2005. Control subjects were matched to case patients on the number of days from the time of transplant. Cox proportional hazards models were used to identify risk factors for VTE., Results: Twenty-four patients had deep vein thromboses, and 6 patients had pulmonary emboli (3 patients had both) [22% of the cohort]. In multivariate models, older age (p < 0.05), diabetes mellitus (p = 0.03), and pneumonia (p = 0.02) were associated with a higher rate of VTE., Conclusions: VTE is a frequent complication of lung transplantation. Older age, diabetes, and pneumonia increase the rate of VTE. Future studies of intensive VTE prophylaxis may be warranted.

The development and progression of invasive uterine cervical carcinomas appear to be associated with the progressive loss of sensitivity to transforming growth factor-beta (TGFbeta)-mediated cell cycle arrest. In order to identify possible molecular mechanisms responsible for TGFbeta resistance, we screened the 7 exons of the type II (TbetaR-II) TGFbeta receptor and the 9 exons of the type I (TbetaR-I) TGFbeta receptor genes for mutations in 16 paraffin-embedded primary invasive cervical carcinoma specimens. In one of these carcinomas, we found a novel G-->T transversion in exon 3 of TbetaR-II that introduces a premature stop codon (E142Stop) and presumably results in the synthesis of a truncated soluble exoreceptor. In one tumor, a silent A-->C transversion mutation that may affect mRNA splicing was present in exon 6 of TbetaR-I. In addition, 7 of 16 cases were heterozygous for a G-->A polymorphism in intron 7 of TbetaR-I. Finally, we identified a 9 base pair in-frame germline deletion in exon 1 of TbetaR-I resulting in loss of 3 of 9 sequential alanine residues at the N-terminus in 6 of 16 cases. Analysis of specimens from case-control studies indicated that carriers of this del(GGC)3 TbetaR-I variant allele may be at a increased risk for the development of cervical carcinoma (p=0.22). Furthermore, the response of cells expressing the variant receptor to TGFbeta was diminished. Our results support the notion that diverse alterations in the TGFbeta signaling pathway may play a role in the development of cervical cancer.