Molecular Profiling of Computed Tomography Screen-Detected Lung Nodules Shows Multiple Malignant Features

Abstract

Rationale and Purpose: Low-dose spiral computerized axial tomography (spiral CT) is effective for the detection of small early lung cancers. Although published data seem promising, there has been a significant degree of discussion concerning the potential of overdiagnosis in the context of spiral CT -based screening. The objective of the current study was to analyze the phenotypic and genetic alterations in the small pulmonary malignancies resected after detection in the University of Navarra/International Early Lung Cancer Action Project spiral CT screening trial and to determine whether their malignant molecular features are similar to those of resected lung tumors diagnosed conventionally. Experimental Design: We analyzed 17 biomarkers of lung epithelial malignancy in a series of 11 tumors resected at our institution during the last 4 years (1,004 high-risk individuals screened), using immunohistochemistry and fluorescence in situ hybridization (FISH). A parallel series of 11 gender-, stage-, and histology-matched lung cancers diagnosed by other means except screening was used as control. Results: The molecular alterations and the frequency of phenotypic or genetic aberrations were very similar when screen-detected and nonscreen-detected lung cancers were compared. Furthermore, most of the alterations found in the screen-detected cancers from this study were concordant with what has been described previously for stage I-II lung cancer. Conclusions: Small early-stage lung cancers resected after detection in a spiral CT-based screening trial reveal malignant molecular features similar to those found in conventionally diagnosed lung cancers, suggesting that the screen-detected cancers are not overdiagnosed. (Cancer Epidemiol Biomarkers Prev 2006;15(2):373 -80)

The Convergent Development of Molecular-Targeted Drugs for Cancer Treatment and Prevention

“…Identified by CT and a subsequent fine needle aspiration, group 1 patients would have atypical alveolar or bronchioloalveolar proliferation likely denoting adenomatous hyperplasia or bronchioloalveolar carcinoma (although microinvasion cannot be ruled out) and group 2 patients would have early-stage cancer (some with adenomatous hyperplasia or bronchioloalveolar carcinoma in proximate tissue). The finding of similar molecular profiles in CT screening -identified early tumors and clinically detected tumors supports the relevance of CT screening -detected cancer to drug development (51,52). Patients would be randomized to one or more doses of a molecular-targeted agent or placebo.…”

EUELC project: a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration

“…The information relating the patient, EBTB number, barcodes and locations of samples is stored in a database. A copy of the cytology reports for each patient is retained by the Partner We have also set up protocols for automatic immunohistochemical procedures for hnRNP A1, ASF/SF2 and alpha CP4 [14][15][16]. In addition, a cross-laboratory validation was performed for these markers.…”

Copy number gains on 5p15, 6p11-q11, 7p12, and 8q24 are rare in sputum cells of individuals at high risk of lung cancer

“…Therefore, advancing of LC diagnosis is the most important single factor expected to improve the survival rates. Screening trials using low-dose spiral computerized axial tomography are currently in progress to investigate whether earlier diagnosis can reduce the LC mortality [4][5][6][7]. Collection of induced sputum samples is a non-invasive technique potentially useful as a supplementary approach that can be used for conventional cytology and for development of cancer biomarkers.…”

“…Using the receiver operator characteristics curve, they determined the cut-off value for a malignant case to be six or more abnormal cells in bronchial washing specimens. Later on, this probe set has been applied to several types of specimens such as bronchial brushings, cultured bronchial epithelial cells, fine-needle aspirates, touch-preparations of lung tumour tissue, and sputa obtained from patients with suspected or known LC as well as from individuals with non-malignant lung disorders such as chronic obstructive pulmonary disease (COPD) [6,[15][16][17][18][19][20].…”

“…The analysis was performed on epithelial cells in induced sputum smears collected from asbestos-exposed workers and heavy tobacco smokers in addition to LC patients and healthy non-smoking individuals. In this article, we also review the previous studies describing the use of LAVysion TM probe set [6,[14][15][16][17][18][19][20]]. …”