Author of

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  P35 - Pathology - Genomics (ID 105)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 34745

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    P35.11 - Molecular Profiling Can Distinguish Multiple Lung Primary Tumors From Intrapulmonary Metastases (ID 1492)

    00:00 - 00:00  |  Presenting Author(s): Wei Cheng
    • Abstract
    • Slides

    Introduction
    

    Multiple lung primary tumors (MP) and intrapulmonary metastases (IM) are two types of multifocal lung cancers (MLCs), with comparable pathological manifestation but distinctive treatment regiments. Although, histologic assessments remain to be the mainstay diagnostic method to distinguish MP from IM, molecular profiling is finding increasing application. However, the clinical significance of next generation sequencing (NGS)-based molecular assessment in differential diagnosis remains elusive.

    Methods
    

    Targeted sequencing was performed on 36 distinct lung tumor lesions from 16 patients diagnosed with multiple lung primary cancer by radiological and histopathological assesments. 3 patients had more than 2 lesions. A panel consisting of 520 cancer-related genes was used for molecular profiling. Pairing analysis was performed to reveal the differences in somatic mutation profiles of multiple lung tumors in each patient. All samples were adenocarcinoma except for one, which was sarcomatous carcinoma.

    Results
    

    Colletively, our analysis revealed 331 mutations from 36 tumor samples with 1 lesion from P13 had no mutation detected from this panel. Mutation landscapes of paired tumor tissues from 12 patients (75%) showed mututally exclusive pattern, suggesting multiple lung primary cancer. Shared mutations were observed in paired tumors from 4 patients. P 15 (patient 15) only had EGFR (p.L858R) shared by the 2 lesions. Since this is a common mutation in lung adenocarcidoma , we cannot rule out the possibility of MP. P5 had 15 and 10 mutations detected from each lesion with 3 common missense mutations: EMSY, SMAD4, and POM121L12 as well as 3 common gene copy number amplifications: SDHA, TERT, and EGFR. Based on the similar molecular profile, the 2 lesions are predicted to be primary-metastatic pair. P10 had 4 lesions (A-D, 3 pure ground-glass nodules GGNs and 1 mixed GGN). Among them, 2 lesions (A and B) had EGFR (p.L747_T751del) and RBM10 (p.V467fs) in common. Lesions A, C and D had no common mutations detected. P16 had 3 lesions, all of them are pure GGNs. Two of them shared EGFR (p.L858R) and ATRX (p.S1012A). Thus, based on the molecular landscape of these 2 patients, we cannot exclude the possibility of intrapulmonary metastases. In addition, shared mutations observed in P16 and P10 provide evidence that GGNs might result from early metastasis.

    Conclusion
    

    Our study revealed a high consisitency between molecular profiling and conventional diagnostic methodologies, suggesting that molecular profiling can potentially facilitate the distinction of multiple lung primary tumors from intrapulmonary metastases. It may serve as a supplementary method to histopathologic analysis in diagnosis. In addition, our results provide new genomic clues of cancer invasion in GGNs.

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