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Chunyan Wu



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    MA09 - Lung Cancer Surgical and Molecular Pathology (ID 908)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 15:15 - 16:45, Room 202 BD
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      MA09.11 - Genomic Landscape and its Correlation with TMB, CD8 TILs and PD-L1 Expression in Chinese Lung Squamous Cell Carcinoma (ID 12370)

      16:25 - 16:30  |  Author(s): Chunyan Wu

      • Abstract
      • Presentation
      • Slides

      Background

      The current study aimed to comprehensively depict the genomic landscape of Chinese lung squamous cell carcinoma (LSCC) and investigate its correlation with tumor mutation burden (TMB), CD8 tumor infiltrating lymphocytes (TILs) density and PD-L1 expression.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Whole-exome sequencing (WES) were performed on tumor tissue collected from 189 patients with surgically resected LSCC. TMB was defined as total number of nonsynonymous single nucleotide and indel variants. High TMB was defined as greater than 75th percentile. CD8+ TILs and PD-L1 expression were assessed by immunohistochemistry. We determined the 5% of CD8+ TIL or PD-L1 expression as the cut-off point for high/low CD8+ TIL or PD-L1 positive/negative expression.

      4c3880bb027f159e801041b1021e88e8 Result

      We found recurrent mutations (>5%) in 8 genes, including TP53, KMT2C, NFE2L2, KEAP1, CDKN2A, PTEN and FBXW7. FGFR1 and PIK3CA amplifications were found in 19% and 11% of samples. 24.9% of patients had high TMB. Except for expected differences by smoking status, baseline clinical variables were similar between those with high and low TMB. Interestingly, FGFR1, PIK3CA or SOX2 amplification was independently associated with higher TMB (P=0.020, P=0.017, P=0.029; respectively). Patients with copy number variations had significantly higher TMB than those without (P=0.009). Positive PD-L1 and CD8+ TILs expression were identified in 24.3% and 78.8% of all cases. Baseline features were comparable between those with positive and negative CD8+ TIL or PD-L1 expression. NFE2L2 mutation and PIK3CA amplification were independently associated with significantly higher PD-L1 expression (P=0.003, P=0.014; respectively). TP53 mutations were associated with higher CD8+ TILs expression (P=0.008), but FGFR1 amplification was correlated with lower CD8+ TILs expression (P=0.042). Of note, there is no association between TMB and PD-L1 expression (r=0.052, P=0.476), or CD8+ TILs expression (r=0.026, P=0.718). None of TMB, PD-L1 and CD8+ TIL expression could individually predict overall survival (OS). However, combination of TMB and PD-L1 could stratify total populations into two groups with distinct prognosis. Patients with negative PD-L1 expression and high TMB had the worst prognosis (P=0.008). Additionally, combination of TMB and CD8+ TIL expression could also divide total populations into two groups with different prognosis (worst prognosis in negative CD8+ TIL expression and high TMB, P=0.022).

      8eea62084ca7e541d918e823422bd82e Conclusion

      This was the first and most large-scale study to comprehensively portray genomic landscape of Chinese LSCC. The current study provides several meaningful and referential findings for the future design of clinical trials in LSCC, especially immunotherapy based on immune checkpoint inhibitors.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    OA03 - Advances in Lung Cancer Pathology (ID 897)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 205 BD
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      OA03.01 - The Immunophenotyping and Genomic Characteristics of Pulmonary Sarcomatoid Carcinoma: Pleomorphic, Spindle Cell and Giant Cell Carcinoma (ID 12239)

      10:30 - 10:40  |  Presenting Author(s): Chunyan Wu

      • Abstract
      • Presentation
      • Slides

      Background

      Pulmonary sarcomatoid carcinoma (PSC) is a poorly differentiated non-small cell lung cancer (NSCLC) and comprises a diagnostically and therapeutically challenging group of tumors. We explored the immunohistochemical characteristics and genetic profiles of PSC (except carcinosarcoma and pulmonary blastoma)

      a9ded1e5ce5d75814730bb4caaf49419 Method

      A total of 432 cases with surgically resected undifferentiated NSCLC (121 solid adenocarcinomas (ADC), 98 non-keratinizing squamous cell carcinomas (SQC), 118 large cell carcinomas (LCC) and 95 sarcomatoid carcinomas) were reviewed. Expression of epithelial-mesenchymal transition (EMT) markers (Cytokeratin (CK), Vimentin (Vim) and zinc-finger E-box binding homeobox 1 (ZEB1)) were studied by immunohistochemistry. 8 therapeutically-relevant genetic alterations(EGFR/BRAF/KRAS/HER2/MET exon 14 mutations and ALK/ROS1/RET fusion)of sarcomatoid carcinomas were detected by Capture-based targeted sequencing

      4c3880bb027f159e801041b1021e88e8 Result

      The expression of CK was almost positive in ADC, SQC and LCC, which of sarcomatoid component (SC) of PSC was observed positively only in 80/95(84.2%). Although vim expression was higher (88/95, 92.6%) in SC, it was also positive in ADC (37/121, 30.6%), SQC (14/98, 14.3%), LCC (12/118, 10.2%), respectively. In the contrast, SC was detected with 100% ZEB1 expression in PSC (95/95). ZEB1 expression was focal positive only in 1 cases of SQC (1/98, 1.0%). In ADC and LCC, no ZEB1 expression was found. The expression of ZEB1 had higher specificity (99%) and sensitivity (100%) than Vim expression in SC of PSC. The most frequent mutation genes were KRAS (18/58, 31.0%), EGFR (6/58, 10.3%), MET exon 14 (7/58, 12.0%) and no BRAF/HER2/ALK/ROS1/RET alteration were detected.

      8eea62084ca7e541d918e823422bd82e Conclusion

      ZEB1 was a useful differential diagnostic marker for PSC. Targeted mutations testing may be useful for classifying and managing PSC patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.09 - Pathology (Not CME Accredited Session) (ID 941)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.09-10 - Targeted Sequencing of Pulmonary Enteric Adenocarcinoma Reveals Distinctive Mutation Profile from Conventional Type of Lung Adenocarcinoma (ID 12468)

      16:45 - 18:00  |  Author(s): Chunyan Wu

      • Abstract
      • Slides

      Background

      Pulmonary primary enteric adenocarcinoma (PEAD) is a rare subtype of lung cancer, which is defined in the new edition of 2015 WHO classification. However, genetic profiling and information about targeted therapy of PEAD remain unclear.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Resected 56 cases of PEAD were retrospectively reviewed. The pathological diagnosis of PEAD was confirmed by immunohistochemistry based on morphology and over 1 year’s follow-up. We use targeted ultra-deep sequencing to test 56 therapeutically relevant genes alterations of PEAD.

      4c3880bb027f159e801041b1021e88e8 Result

      The majority of PEAD patients were male (41/56, 73.2%). Molecular analysis revealed that KRAS was the most frequently mutated gene (18/56, 32.1%) with no targetable mutation co-existence, and then EGFR (9/56, 16.1%), ERBB2 exon 20 insertion mutations (4/56, 7.1%) and ERBB2 amplification (8/56, 14.3%). 3 cases harboring rare fusion genes were identified, TACC3-FGFR3 (2/56, 3.6%) in 2 cases and CD74-NRG1 in one case, respectively. APC gene mutation was negative in all cases. One postoperative patient with EGFR exon 21 L858R mutation was treated with 4 cycles’ NP chemotherapy regimen. PET-CT found the progression lesion of right rib. Treatment was switched to gefitinib for 8 monthly cycles. Response was poor with brain metastasis. Patient received gamma knife treatment. And then, the results of molecular testing showed no EGFR T790M mutation by using the pleural effusion specimen. Pemetrexed regimen was employed to patient. Follow-up of the patient remains ongoing.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Pulmonary primary enteric adenocarcinoma exhibited distinctive features of genetic profile. Despite KRAS appearing as the most important mutated gene in PEAD tumors, PEAD patients with sensitive mutations were eligible for targeted therapy.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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