Cytogenetic findings in lung cancer that illuminate its biological history from adenomatous hyperplasia to bronchioalveolar carcinoma to adenocarcinoma: A case report

Abstract

The biological and chronological evolution of lung cancer remain to be fully elucidated. A multi-step carcinogenesis hypothesis suggests a progression from atypical adenomatous hyperplasia (AAH) through bronchioalveolar carcinoma (BAC) to invasive adenocarcinoma (AC), but to date this has not been formally demonstrated. We report a case of a patient diagnosed by computed tomography (CT) with lung cancer in the superior right lobe who also presented with a pure ground-glass opacity (GGO) in the inferior lobe, while the middle lobe appeared normal. Following pneumonectomy, cytogenetic analysis successfully performed on spontaneous metaphases obtained by the direct method from samples of the three lung lobes showed the presence of three clonal cell populations, each progressively having increased karyotype complexity. Fluorescence in situ hybridization (FISH), performed using ALK (2p23) break probe and ALK/EML4 t(2;2);inv(2) fusion probe, showed a normal pattern for all specimens. Histological evaluation confirmed the presence of AC in the superior right lobe and classified the GGO lesion as BAC and the normal tissue of the middle lobe as AAH. To the best of our knowledge, this is the first case in which the cytogenetic study of spontaneous metaphases showed a clear clonal relationship among AC, BAC and AAH present simultaneously in different lobes of the same lung. This case appears to indicate that the entire lung was somehow predisposed to a neoplastic transformation starting with a diffuse AAH characterized by high proliferative activity. Moreover, the 5q13 region involved in the translocation shared by BAC and AC contains at least 4 genes encoding important regulators of the cell cycle that may be considered new molecular markers of lung cancer.

Lung cancer in which the hypothesis of multi-step progression is confirmed by array-CGH results: A case report

“…Results were analyzed according to Human Genome version 19 (Hg19) ( 10 ). The data obtained from the a-CGH study confirmed the hypothesis of multistep progression of the lung cancer that was previously made on the basis of the previously reported, limited cytogenetic results ( 8 ). The three different lesions shared losses in 1p, 4p, 9q, 11p, 12p, 14q, 15q, 16p, 16q and 22q ( Table I ).…”

“…In the present study the array-comparative genomic hybridization (a-CGH) technique was applied on three DNA samples from a patient presenting AAH, BAC and AC in one lung, in order to confirm the previous cytogenetic data for that patient ( 8 ), suggesting a clonal evolution of these lesions and the pre-neoplastic nature of AAH.…”

“…Histological evaluation lead to a diagnosis of AC with a BAC component in the upper right lobe, BAC in the inferior lobe and AAH in the middle lobe. Following pneumonectomy, a cytogenetic investigation of spontaneous metaphases obtained using a direct method from the three different samples was performed, as previously reported ( 8 , 9 ). The karyotypes showed a clear clonal association among AC, BAC and AAH ( 8 ).…”

Protection Against Lung Cancer Patient Plasma-Induced Lymphocyte Suppression byGanoderma LucidumPolysaccharides

“…Only 16% of lung cancers are diagnosed when the disease is still localized, while the majority of lung cancers are diagnosed at later stages, which results in a high mortality rate. The initiation and progression of the lung cancer is associated with many factors, including immunity, cytogenetics [35], epithelial-mesenchymal transition [36], and sunlight [37]. Although the immune system with the potential to destroy tumor cells serves as the final natural defense against tumor development, tumor cells can escape from the host immune system by numerous mechanisms which suppress anti-tumor immune function [38].…”

Translating Curcumin to the Clinic for Lung Cancer Prevention: Evaluation of the Preclinical Evidence for Its Utility in Primary, Secondary, and Tertiary Prevention Strategies

“…There is currently ambiguity regarding the best way to treat early disease. Pulmonary nodules and atypical adenomatous hyperplasia are characterized by a radiologic ground-glass opacity, some of which may remain stable for years, and others which may be the precursors of adenocarcinomas (Nakahara et al, 2001;Jeremy George et al, 2007;Bettio et al, 2012). With improved radiology in ground-glass opacity detection, and the question as to whether surgical intervention is appropriate in all cases, these lesions may present an ideal target for chemopreventive intervention.…”