Adenocarcinomas with predominant ground-glass opacity: correlation of morphology and molecular biomarkers

To retrospectively identify successive changes in peripheral lung adenocarcinoma that feature dominant ground-glass opacity (GGO) at computed tomography (CT) and correlate with biomolecular markers.

The institutional review board approved this retrospective study, and all 25 patients provided informed consent. Patients with lung adenocarcinomas smaller than 3 cm in diameter in whom tumor growth could be evaluated with CT before surgery were included. Two thoracic radiologists evaluated tumor growth by analyzing GGO type (pure or mixed) and size increases. Immunohistochemistry of the p53 protein and molecular analysis of the epidermal growth factor receptor (EGFR) and K-ras genes were performed. The Fisher exact test was used to assess statistical significance.

Tumor size increased in 19 of 25 patients (76%) during the observation period. The CT changes in 19 patients were classified into four patterns: persistent pure GGO (n = 8), change from pure to mixed GGO (n = 3), mixed GGO with growth of solid component (n = 4), and mixed GGO with growth of GGO component (n = 4). The remaining six patients (24%) had pure GGO without any interval changes. Staining for p53 was negative in all 14 patients with pure GGO and positive in six of 11 patients (55%) with mixed GGO (P < .01). In these six patients appearance or growth of the solid component was seen. EGFR mutations were found in both pure (36%) and mixed (45%) GGO lesions (P = .70).

Lung adenocarcinomas with a dominant GGO often possess EGFR mutations. Interval changes in the solid component may be related to p53 inactivation.