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Kota Ishizawa



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    MA18 - Advances in Diagnosis of Common Types of NSCLC (ID 145)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Pathology
    • Presentations: 1
    • Now Available
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      MA18.02 - S100A10 Upregulation Associates with Poor Prognosis in Lung Squamous Cell Carcinoma (Now Available) (ID 2836)

      11:30 - 13:00  |  Author(s): Kota Ishizawa

      • Abstract
      • Presentation
      • Slides

      Background

      S100A10 is one of the members of S100 protein family. This molecule predominantly functions in a complex with annexin A2, and stimulates plasminogen activator (tPA)-dependent plasmin formation. Plasmin cleaves and activates metalloproteases (MMPs). Several studies have established that plasmin is an important protease involved in cancer cell migration and invasion. Expression of the S100 protein family is detected in many human cancers and has been related to a poorer prognosis, but relationship between S100A10 expression and progression of human lung cancer has not been clarified. In this study, we focused on S100A10 and aimed to clarify its effect to progression in lung adenocarcinomas and lung squamous cell carcinomas (SCCs).

      Method

      We investigated expressions of S100A10 and MMPs by immunohistochemistry in resected 98 primary lung adenocarcinomas and 120 primary lung SCCs, and its associations with clinicopathological parameters were evaluated. S100A10-positivity was defined when more than 10% tumor cells showed positive staining. In lung SCC cases, we particularly evaluated cancer cell surface at the invasive front. Kaplan-Meier analysis and Cox proportional hazard models were used to estimate the effect on survival. Next we observed the expression of S100A10 in 6 lung adenocarcinoma and 6 lung SCC cell lines, and performed siRNA-mediated knockdown against S100A10 in highly-expressing cell lines.

      Result

      Seventy-four (78.6%) of 98 adenocarcinomas were S100A10-positive cases, and correlations with poorer prognosis (p=0.0413), lymphatic invasion (p=0.0335), and expression of MMP2 (0.0081), were observed, although S100A10 expression was not an independent predictor of a poorer survival in the multivariable analysis (HR 1.7334, 95%CI 0.4340-11.523, p=0.4647). In the same way, 33 (27.5%) of 120 SCCs showed S100A10-positive staining and correlation with poorer prognosis (p=0.0094), p-TNM stage (p=0.0119), nodal involvement (p=0.0006), lymphatic invasion (p=0.0005), and tumor size (p=0.0003) were observed. As for lung SCCs, S100A10 expression was an independent predictor of a poorer survival in the multivariable analysis (HR 9.5916, 95%CI 1.0702-128.208, p=0.0434). Then we performed knockdown of S100A10 in lung cancer cell lines and found that knockdown of S100A10 suppressed cell proliferation in adenocarcinomas and SCCs, and invasion in adenocarcinomas.

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      Conclusion

      In this study, we found that S100A10 expression associates with poorer survival in lung SCCs, but not in lung adenocarcinoma. Our present results suggest that S100A10 protein plays an important role in proliferation of lung cancer, possibly in association with invasion by MMPs. Future studies are necessary to further understanding of importance of S100A10 in progression of human lung cancer, including some differences between histological subtypes.

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