7555 Background: In the case of patients with multiple lung adenocarcinomas (ADCs) (whether synchronous or metachronous), the distinction of intrapulmonary metastases from independent primaries is clinically important as it impacts staging and thus therapeutic strategy. Currently the distinction is made based principally on histology of the tumor. Molecular profiling is becoming a routine diagnostic procedure for lung cancer to help treatment decision-making. Thus, we sought the role of mutation assays to differentiate multiple primaries from metastases. Methods: 45 synchronous and 37 metachronous cases of multiple tumors were obtained at 103 surgeries in 68 patients. Each of the resultant 156 tumors was tested with the SNaPshot multiplex PCR genotyping assay and each case, based on molecular profiling, was classified as synchronous multiple primaries (SP), metachronous primaries (MP), synchronous intrapulmonary metastases (SM), or metachronous metastases (MM). Each case was also classified into 4 groups by a comprehensive histologic analysis. Clinical outcomes were compared between multiple primaries (SP and MP) and metastases (SM and MM) in the molecular and histologic analyses using Log-rank test. Results: Based on histology alone, SP were present in 37 cases, MP in 32, SM in 8 and MM in 5. The molecular results were interpreted as SP in 25, MP in 21, SM in 10 and MM in 11. 15 of the 82 cases were non-informative, since no mutations were identified in any lesions. Of the 67 cases harboring mutations, 21 (31%) showed discordant results consisting of 16 with SP or MP by histology and SM or MM by molecular profiling. 5 cases showed the opposite results. Molecular profiling showed a trend toward the 5-year survival of the patients with metastases being shorter than those with multiple primaries (57 months vs. 87 months, P=0.068), which was not observed by histology (P=0.84). Conclusions: Although its performance is limited by non-informative results in 18% of cases of multiple ADCs, SNaPshot profiling for clinical use appears to be useful in determining whether multiple ADCs are primaries or metastases. Thus, it may allow for more accurate staging and optimal therapeutic management.
ES25.04 Multiple Pulmonary Lesions: Metastasis vs Multiple Primaries, From Martini's Criteria to Molecular Profiling
