EGFR gene copy number in adenocarcinoma of the lung by FISH analysis: Investigation of significantly related factors on CT, FDG-PET, and histopathology

Abstract 

It has been suggested that a high EGFR gene copy number may be an indicator of good response to EGFR tyrosine kinase inhibitor therapy and a marker of poor prognosis in NSCLC. However, imaging features related to EGFR gene copy number status in adenocarcinoma are still unknown. We therefore retrospectively analyzed CT, FDG-PET, and histopathologic slides of surgical resected lung adenocarcinoma in 132 patients. Tumor characteristics on preoperative chest-CT, such as, GGO proportions, tumor diameters, and cavitation; FDG-PET SUV_max; and histopathologically determined differentiation degrees and tumor subtypes were evaluated. EGFR gene copy number status was categorized as FISH-positive or -negative. FISH-positivity was found in 53 patients (40.2%) and was significantly more frequent in tumors with a SUV_max>7.0 (P=0.007). Furthermore, FISH-negativity was found to be more frequent in tumors with a GGO>50% (P=0.023) and diameter <15.5mm (P=0.006) on CT, or a well-differentiated histopathology (P=0.002). Moreover, the frequency of FISH-positivity increased as SUV_max increased (P=0.0008) and as the proportion of GGO decreased (P=0.01). SUV_max>7.0 was an independent predictor of FISH-positive results (odds ratio, 3.941; 95% CI, 1.691–9.182; P=0.01). In conclusion, a high SUV_max on FDG-PET was significantly related to FISH-positive results. A high proportion of GGO, small tumor diameter on CT, and a well-differentiated histopathology were more frequent in FISH-negative adenocarcinomas.

Abbreviations: NSCLC, non-small cell lung cancer, EGFR, epidermal growth factor receptor, TK, tyrosine kinase, BAC, bronchioloalveolar carcinoma, GGO, ground-glass opacity, FISH, fluorescence in situ hybridization, SUV_max, maximum standardized uptake value, CI, confidence interval

Keywords: EGFR, FISH, EGFR gene copy number, CT, FDG-PET, Adenocarcinoma, Lung