Epidermal growth factor receptor mutation and pathologic-radiologic correlation between multiple lung nodules with ground-glass opacity differentiates multicentric origin from intrapulmonary spread.
BACKGROUND
No standard guidelines detailing recommendations for the selection and treatment for multiple lung nodules with ground-glass opacity (GGO) have been established. For treatment decision, we analyzed epidermal growth factor receptor (EGFR)/K-ras somatic aberrations and pathologic-radiologic correlation in multiple lung nodules presented as GGO to differentiate multifocal lesions from intrapulmonary spread.


METHODS
Twenty-four patients with multiple lung nodules presented as GGO were identified to investigate somatic mutations of EGFR (exon 18-21) and K-ras (codons 2, 13, and 61). This series included 18 atypical adenomatous hyperplasias (AAH), 15 bronchioloalveolar carcinomas (BAC), and 23 adenocarcinomas (ADC) obtained from 24 patients.


RESULTS
High frequency of discordant EGFR mutations (17 of 24, 70.8%) could discriminate tumor clonality (18 of 24, 75%) of multiple lung neoplastic nodules presented as GGO. EGFR mutations were common in AAH (38.9%), BAC (46.7%), and ADC (39.1%). In case 4, AAH and BAC had different mutational changes, and in case 10, the BAC lesion contains EGFR mutation that is not in the invasive ADC. In case 17, the BAC had more mutational changes than the carcinoma. The pure GGO appearance in the radiologic examination corresponded preinvasive pathologic change.


CONCLUSIONS
This study showed that synchronous BAC and/or ADC can have different EGFR or K-ras mutational profiles suggesting these lesions arise as independent events rather than intrapulmonary spread or systemic metastasis. This has significant implication in staging and treatment. These findings might be a clue to establish guidelines of the multiple neoplastic lung nodules with GGO.
Chung
Jin-Haeng
JH
Department of Pathology, Seoul National University College of Medicine, Seongnam, Gyeonggi-do, Republic of Korea.
Choe
Gheeyoung
G
Jheon
Sanghoon
S
Sung
Sook-Whan
SW
Kim
Tae Jung
TJ
Lee
Kyung Won
KW
Lee
Jae Ho
JH
Lee
Choon-Taek
CT
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002278:Carcinoma in Situ / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D004273:DNA, Neoplasm / Q000235:genetics; D003937:Diagnosis, Differential; D066246:ErbB Receptors / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006965:Hyperplasia / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011230:Precancerous Conditions / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000097:blood / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D014057:Tomography, X-Ray Computed; D018631:ras Proteins / Q000097:blood / Q000235:genetics
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins