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C. Wu
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MINI 10 - ALK and EGFR (ID 105)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:T. Yap, T. Li
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 1a-1f
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MINI10.02 - Intratumoral Heterogeneity of ALK-Rearranged and ALK/EGFR Co-Altered Lung Adenocarcinoma (ID 685)
16:45 - 18:15 | Author(s): C. Wu
- Abstract
- Presentation
Background:
Genetic intratumoral heterogeneity has a profound influence on the selection of clinical treatment strategies and addressing resistance to targeted therapy. The purpose of our study is to explore the potential effect of intratumoral heterogeneity on both the genetic and pathologic characteristics of ALK-rearranged lung adenocarcinoma (LADC).
Methods:
We tested ALK fusions and EGFR mutations in 629 LADC patients by using laser capture microdissection (LCM) to capture spatially separated tumor cell subpopulations in various adenocarcinoma subtypes and test for ALK fusions and EGFR mutations in ALK-rearranged, EGFR-mutated, and ALK/EGFR co-altered LADCs in order to compare the oncogenic driver status between different tumor cell subpopulations in the same primary tumor.
Results:
Among the 629 patients, 30 (4.8%) had ALK fusions, 364 (57.9%) had EGFR mutations, and 2 had ALK fusions coexisting with EGFR mutations. Intratumoral heterogeneity of ALK fusions was identified in 9 patients by RT-PCR. In the 2 ALK/EGFR co-altered patients, intratumoral genetic heterogeneity was observed both between different growth patterns and within the same growth pattern. Genetic intratumoral heterogeneity of EGFR mutations was also identified in EGFR-mutated NSCLC. ALK fusions were positively associated with a micropapillary pattern (P=0.002) and negatively associated with a lepidic pattern (P=0.008) in a statistically-expanded analysis of 900 individual adenocarcinoma components, although they appeared to be more common in acinar-predominant LADCs in the analysis of 629 patients.
Conclusion:
Intratumoral genetic heterogeneity was demonstrated to co-exist with histologic heterogeneity in both single-driver and EGFR/ALK co-altered LADCs. As for the latter, one of the dual altered drivers may be the trunk-driver for the tumor.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-027 - Clinicopathologic Study and Prognostic Analysis of Bronchial Mucoepidermoid Carcinoma (ID 1133)
09:30 - 17:00 | Author(s): C. Wu
- Abstract
Background:
Bronchial mucoepidermoid carcinoma (MEC) is a rare type of lung cancer. The present study tried to establish the clinicopathologic characteristics and prognostic factors of patients with this cancer who were treated in Shanghai Pulmonary Hospital. In addition, the common genetic changes were analyzed here.
Methods:
Sixty-four cases of bronchial MEC treated in Shanghai Pulmonary Hospital between 1995 and 2013 were collected for our study. Retrospective cohort study was performed to analyze the relationship between clinical characteristics and prognosis. The common genetic changes of non-small cell lung cancer, such as EGFR, ALK ,ROS1,BRAF, KRAS status were tested.
Results:
All 64 MECs were reconfirmed by pathologists and tumor staging of all patients were reevaluated according to AJCC 7th edition system. There were 35male patients and 29 females with median age of 40.5 years old. Cough and hemoptysis were the most common clinical manifestations. The mean time between symptom appearance and going to see doctors was 8.7months. Fibre optic bronchoscopy confirmed the presence of bronchial tumor in 48 of 64 patients, but only half of them were diagnostic of MEC by endobronchial biopsies. The pathological findings were cellular mixture consisting of mucus-secreting cells, squamous cells and mesenchymal cells. There were 52 and 4 patients who were in an early stage (stage I-II) and stage IIIA at the time of diagnosis. All those patients underwent surgical resection with lymph node sampling and dissection and 10 patients received adjuvant chemotherapy, 2 patients adjuvant radiocherapy. There were 5 and 3 patients in stage IIIB and IV. Among them, 4 were treated by chemotherapy. The median survival time for patients with stage I-II ,IIIA and IIIB-IV were 71months (10-223months), 35 months (5.3-126months) and 4 months (1-51months) respectively. Single factor analysis showed that the early TNM staging (p=0.000), no mediastinal lymph node involvement or N1 involvement (p=0.000) and surgery (p=0.001) were the positive prognostic factors for MEC patients. There was a trend that shorter disease course might benefit for survival (p=0.09). Multi-factor analysis showed that TNM staging was an independent prognostic factor for the patients suffering from bronchial MEC. Genetic testing showed that 1of 38 patient presented T790M mutation, 17 of 32 patients had KRAS positive staining and no BRAF mutation was found. Interestingly, we found 3 ALK rearrangement which accounted for 7.5% of all tested patients.
Conclusion:
TNM staging is an independent prognostic factor for bronchial MEC patients. Mediastinoscopy should be performed on patients who are clinically N2 stage to get precise stage and treatment decision. Early diagnosis and early surgery may improve patients’ survival. For advanced MEC patients, ALK fusion gene may be routinely tested so as to provide patients with more therapy options.
