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H. Xiong



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    P2.12 - Poster Session 2 - NSCLC Early Stage (ID 205)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P2.12-002 - Clinical characteristics and prognosis of lung adenocarcinoma driver mutations from Chinese population (ID 1292)

      09:30 - 09:30  |  Author(s): H. Xiong

      • Abstract

      Background
      Driver gene mutation in lung adenocarcinoma varies greatly among different populations, and lacks of large sample study on Chinese population. The purpose of this study was to identify driver gene mutations or translocations, and to evaluate their association with clinicopathological features and prognosis in Chinese lung adenocarcinoma.

      Methods
      Gene mutations or translocations were detected by fluorescence quantitative PCR in tumor tissues of 762 lung adenocarcinoma patients, including mutations of EGFR, KRAS and BRAF, and translocations of ALK and RET. The correlation of gene mutations/translocations with clinicopathological features was retrospectively analyzed by Chi-square test and logistic regression. Kaplan-Meier survival curves were used to evaluate the correlation of these genes with disease-free survival(DFS) in 314 patients and overall survival(OS) in 564 patients respectively.

      Results
      In the 762 patients with lung adenocarcinoma, the positive rate of gene mutations/translocations involving EGFR, KRAS, ALK, RET and BRAF was 49.6%, 10.0%, 4.5%, 1.7%, 0.5%, respectively, among which there was no mutations of polygenes. This study showed that EGFR mutations were more common in non-smokers or light smokers, lepidic predominant invasive adenocarcinoma subtype, and patients without distant metastasis. KRAS mutations were more common in heavy smokers, mucinous invasive adenocarcinoma subtype, and early stage patients. ALK translocations were more common in patients younger than 55 years old, with solid predominant invasive adenocarcinoma subtypes. RET translocations were more common in patients younger than 52 years old, with solid predominant invasive adenocarcinoma subtypes and patients who have family history of lung cancer. BRAF mutations were more common in mucinous invasive adenocarcinoma subtype. The survival analysis showed that the median OS of EGFR-mutant group was shorter than wild-type group among stage IIIB-IV paitents without targeting therapy(P=0.019); Although KRAS gene mutations in patients with early stage was not related to disease recurrence and survival either, KRAS mutations in stage IIIA patients do contribute to shorter DFS and OS(P=0.018, 0.039); ALK translocations in each stage subgroup were not related to recurrence and survival; Patients with mutations of either EGFR, KRAS, or translocations of ALK as a group showed no significant difference in DFS and OS as compared to those without involvement of any of these genes.

      Conclusion
      The overall driver gene positive rate in this series detected by Q-PCR is 66.3%. Each type of drive gene corresponds to different clinical and pathological features. Patients with ALK or RET gene translocations are more younger, and more likely to be solid predominant invasive adenocarcinoma. EGFR-mutant group has shorter OS than wild-type group among stage IIIB-IV paitents without targeting therapy. KRAS mutations implicate poor prognosis only in patients with stage IIIA.

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    P3.18 - Poster Session 3 - Pathology (ID 177)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P3.18-010 - 5 Driver genes in Chinese Female Lung Adenocarcinoma (ID 1898)

      09:30 - 09:30  |  Author(s): H. Xiong

      • Abstract

      Background
      Currently, 5 driver genes (EGFR, K-RAS, B-RAF, ALK, RET) related to lung cancer have been widely explored and become new targets of NSCLC, however no report has been found in Chinese female lung adenocarcinoma, who were prone to EGFR mutations and therefore, are the targeted populations for TKIs therapy.

      Methods
      FFPE-tissues from 310 female lung adenocarcinoma adopted in Hunan province or Henan province between 2000 and 2012 were investigated. Oncogenic alterations in newly found 5 driver genes were analyzed. For EGFR, K-RAS and B-RAF mutation detection, ARMS was performed. The reverse transcription and real-time PCR were performed either to detect all ALK and RET fusions using primers specific to known rearrangement or to detect ALK and RET expression by primers specific to TK domain. Sequencing was further applied to confirm the subtypes of fusions.

      Results
      Among 310 samples, 149 (48.1%) EGFR mutations, 16 (5.2%) KRAS mutations, 0 (0%) BRAF mutations, 23 (7.4%) ALK fusions and 5 (1.6%) RET fusions were detected. Deletions in exon 19 and L858R in exon 21 account for the major EGFR mutations, representing 97 (65.1%) and 41 (27.5%), respectively. Only EML4-ALK fusion but no other ALK fusions were found. Further research demonstrated that cases (22, 95.6%) with high ALK expression were often accompanied by EML4-ALK fusion and poorly differentiated adenocarcinoma. Two RET fusions, namely, KIF5B-RET and CCDC6-RET were found, with 2 cases and 3 cases, respectively. The ratio of RET/ABL mRNA levels was significantly higher in CCDC6-RET samples with poorly differentiated adenocarcinoma. However, with KIF5B-RET fusion, the situation was more complex. Relatively high RET/ABL mRNA expression was detected in one KIF5B-RET sample with moderately differentiated adenocarcinoma, while no RET expression was detected in other two KIF5B-RET samples with highly differentiated adenocarcinoma.

      Conclusion
      This is the first research about the oncogenic alterations of 5 important driver genes in Chinese female lung adenocarcinoma, as well as the correlation between ALK fusion and ALK expression or between RET fusion and RET expression, thus laying good foundation for understanding the genetic mutation spectrum in female lung adenocarcinoma.