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W. Cai



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    P1.18 - Poster Session 1 - Pathology (ID 175)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P1.18-001 - The prevalence and clinicopathologic feature of ALK, ROS1 and RET fusions in East Asian patients with lung adenocarcinoma (ID 49)

      09:30 - 09:30  |  Author(s): W. Cai

      • Abstract

      Background
      ALK, ROS1 and RET fusions have been demonstrated as oncogenic drivers in lung cancer. Of these, ALK fusions were shown to occur more frequently in patients with mucinous adenocarcinoma or solid histology with signet-ring cells. The association of ROS1 and RET fusions with the adenocarcinoma component remains unclear. We conducted this study to determine the prevalence and clinicopathologic characteristics of ALK, ROS1 and RET fusions in East Asian patients with lung adenocarcinoma, and investigate the association of the above-mentioned gene fusions with histological subtype of adenocarcinoma according to the IASLC/ATS/ERS Classification.

      Methods
      We screened 620 Chinese patients with histologically confirmed lung adenocarcinoma for ALK, ROS1 and RET fusions using multiplex RT-PCR and validated all fusion-positive patients using direct sequencing. The patterns of gene fusions screened in this study contained EML4-ALK (17 variants), CD74-ROS1, SLC34A2-ROS1, SDC4-ROS1, EZR-ROS1, TPM3-ROS1, LRIG3-ROS1, GOPC-ROS1, KIF5B-RET, CCDC6-RET and NCOA4-RET. The association of ALK, ROS1 and RET fusions with different subtype of adenocarcinoma were analyzed in 331 patients. The data for remaining 289 patients are being analyzed. All patients enrolled in this study were followed up for survival.

      Results
      Of the 620 patients with adenocarcinoma screened, 472 (76.1%) patients were never/light smokers (<10 pack-years), and 148 (23.9%) were smokers (≥10 pack-years), with the median age of 59 (range, 27-82) years; 348 patients were female, accounting for 56.1%. Patients with stage I, II, III, or IV disease accounted for 56.6%, 8.7%, 27.1% and 7.6%, respectively. The prevalence of ALK, ROS1 and RET fusions in this study was 8.1% (50/620), 3.5% (22/620) and 1.9% (12/620), respectively. Among the 331 patients diagnosed by the IASLC/ATS/ERS Classification, 15 patients were identified positive for EML4-ALK fusions (including 8 solid, 2 acinar, 2 colloid, 1 lepidic, 1 papillary and 1 micropapillary predominant), 7 patients were positive for ROS1 fusions (including 2 acinar, 2 papillary, 1 lepidic, 1 solid and 1 mucinous predominant), and 4 patients were positive for RET fusions (including 2 acinar, 1 micropapillary and 1 solid predominant).

      Conclusion
      These fusion-positive patients may have unique pathologic feature compared with fusion-negative patients. EML4-ALK fusions were shown to occur in solid predominant adenocarcinoma with a higher frequency in this study. The association of ALK, ROS1 and RET fusions with the subtype of lung adenocarcinoma and the data of survival are being analyzed in all patients and will be presented at the conference.