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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 ␤ (TGF-␤) receptor, suggesting downregulation of TGF␤RII is an early event in lung adenocarcinoma metastasis. Keywords: adenocarcinoma; lung cancer; microarray analysis; neoplasm invasiveness; transforming growth factor-␤ Lung cancer, the leading cause of cancer death in the United States, with 163,000 deaths expected in 2005, is also the leading cause of cancer death worldwide, with 1.1 million annual deaths (1). In contrast to other common neoplasms in breast, colon, and prostate, which are predominantly adenocarcinoma, only 40% of lung cancers are adenocarcinomas. Within the subtype of non-small cell lung carcinoma, all tumors are treated similarly without regard to biological heterogeneity, which may be associated with histologic subclassification. The poor outcome of lung cancer compared with other common cancers (15 vs. 62-97% average 5-year survival) is partly attributable to the current limited ability to distinguish fundamental differences in tumor biological predisposition to metastasis that may be associated with histologic heterogeneity. Lung cancer metastasis is frequent; approximately 40% of patients have distant metastases at the time of diagnosis. Furthermore, among patients who present with localized resectable disease, approximately 30% will develop metastases and succumb to their disease within 5 years. Lung cancer metastasis to lymphatics and visceral organ beds via the systemic circulation is the result of several well-characterized, sequentially acquired properties of tumor cells. These steps include the following: enzyme-mediated invasion of organ stroma, circulation in lymphatic or vascular channels, and extravasation and proliferation in distant organ beds (2). Using high-throughput genomic strategies, the molecular programs driving the tumor-stromal interactions that lead to metastases are becoming well characterized, with delineation of roles for transcription factors (3, 4), proteinases, such as matrix metalloproteinase-11 and cathepsin L2 (5), and chemokines, such as CXCL12 and CXCL14 (6).We and other researchers have previously reported molecular signatures discriminative of non-small cell lung carcinoma differentiation and prognosis (7-10). Gene signatures of lung carcinoma prognosis often ...

Patients with an ECG diagnosis of AFL or AT following surgical atrial fibrillation ablation may have multiple tachycardia mechanisms with the right or left atrium as the site of origin. Many of these rhythms may resolve with further maturation of surgical atrial fibrillation ablation (SAFA) lesions or be treatable with antiarrhythmic medication. However, persistent tachyarrhythmias can often be treated successfully with catheter mapping and ablation.

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