Background: Genetic changes that drive the transition from lepidic to invasive cancer development within a radiographic ground glass or semi-solid lung lesion (SSL) are not well understood. Biomarkers to predict the transition to solid, invasive cancer within SSL are needed.
Methods: Patients with surgically resected SSL were identified retrospectively from a surgical database. Clinical characteristics and survival were compared between stage I SSL (n = 65) and solid adenocarcinomas (n = 120) resected during the same time period. Areas of normal lung, in situ lepidic, and invasive solid tumor were microdissected from within the same SSL specimens and next generation sequencing (NGS) and Affymetrix microarray of gene expression were performed.
Results: There were more never smokers, Asian patients, and sub-lobar resections among SSL but no difference in 5-year survival between SSL and solid adenocarcinoma. Driver mutations found in both lepidic and solid invasive portion were EGFR (43%), KRAS (21%), and DNMT3A (5%). CEACAM5 was the most upregulated gene found in solid, invasive portions of SSL. Lepidic and invasive solid areas had many similarities in gene expression, however there were some significant differences with the gene SPP1 being a unique biomarker for the invasive component of a SSL.
Conclusions: Common lung cancer driver mutations are present in in situ lepidic as well as invasive solid portions of a SSL, suggesting early development of driver mutations. CEACAM5 and SPP1 emerged as promising biomarkers of invasive potential in semi-solid lesions. Other studies have shown both genes to correlate with poor prognosis in lung cancer and their role in evolution of semi-solid lung lesions warrants further study.
Keywords: Adenocarcinoma in situ; Ground glass opacity; Lung adenocarcinoma; Microarray; Next generation sequencing; Semi-solid lung nodules.
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