Abstract
ObjectiveHistology grade, subtypes and TNM stage of lung adenocarcinomas are useful predictors of prognosis and survival. The aim of the study was to investigate the relationship between chromosomal instability, morphological subtypes and the grading system used in lung non-mucinous adenocarcinoma (LNMA).MethodsWe developed a whole genome copy number variation (WGCNV) scoring system and applied next generation sequencing to evaluate CNVs present in 91 LNMA tumor samples.ResultsHigher histological grades, aggressive subtypes and more advanced TNM staging were associated with an increased WGCNV score, particularly in CNV regions enriched for tumor suppressor genes and oncogenes. In addition, we demonstrate that 24-chromosome CNV profiling can be performed reliably from specific cell types (<100 cells) isolated by sample laser capture microdissection.ConclusionsOur findings suggest that the WGCNV scoring system we developed may have potential value as an adjunct test for predicting the prognosis of patients diagnosed with LNMA.
Highlights
Based on recommendations from the InternationalAssociation for the Study of Lung Cancer (IASLC), the American Thoracic Society (ATS), the EuropeanRespiratory Society (ERS) and the 2015 World HealthOrganization (WHO), novel classification concepts were introduced for lung adenocarcinoma, including adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA).invasive adenocarcinoma (IA) is classified as lepidic, acinar, papillary, micropapillary or solid subtypes according to their predominant growth pattern [1,2,3]
We developed a new scoring algorithm to assess whole genome copy number variation (WGCNV) changes and found positive correlation trends of median WGCVN scores with the diversified lung non-mucinous adenocarcinoma (LNMA) histological subcategories, five histologic subtypes of IA, and three tiered predominant histologic subtype grades
We reviewed the hematoxylin and eosin (H&E) staining slides from the 10 predominant papillary IA cases, and found 2 high WGCNV score cases had the morphological characteristics of type 3 papillary tumor previously proposed [36]
Summary
Invasive adenocarcinoma (IA) is classified as lepidic, acinar, papillary, micropapillary or solid subtypes according to their predominant growth pattern [1,2,3]. This classification system has subsequently been shown to be important for predicting prognosis and survival [4,5,6,7]. In some studies and clinical practices, a three tiered architectural grading system has been applied, with grade 1 inclusive of AIS, MIA and lepidic predominant IA patterns, grade 2 inclusive of papillary and acinar predominant IA patterns and grade 3 inclusive of micropapillary and solid predominant IA patterns [8,9,10,11]. In recent molecular studies of lung adenocarcinoma, both oncogenic mutations and copy www.cjcrcn.org
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