Intratumoral heterogeneity of lung cancer and its influence on the companion diagnostics

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08373
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Motoi Noriko 国立研究開発法人国立がん研究センター, 中央病院, 医長 (70292878)
• Co-Investigator(Renkei-kenkyūsha): ISHIKAWA Yuichi がん研究会がん研究所, 病理部, 部長 (80222975) ; OKUMURA Sakae がん研究会がん研有明病院, 呼吸器外科, 部長 (40465935) ; NISHIO Makoto がん研究会がん研有明病院, 呼吸器内科, 部長 (00281593)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: Lung Cancer / Biomarker / Tumor heterogeneity / Companion diagnostic / PD-L1 / ALK / MET

Outline of Final Research Achievements

It is one of the urgent issue to establish an appropriate companion diagnostic system to proceed precision medicine in oncology, especially lung cancer in which many targetable genomic and immunological alteration have been explored. The aim of this study is to explore the mechanism of discordancy and inappropriate results in pathological companion diagnostics of lung cancer, especially focusing on its intratumoral heterogeneity. Our results indicated that the morphological heterogeneity was the sum of genomic and epigenomic alterations, and the fundamental driver oncogenic mutation (such as ALK) was retained through progression, then modified by the additional alterations. Of lung cancer with MET exon 14 skipping mutation, morphology and/or IHC based system had low power for screening. Our study suggested the importance of quality control of PD-L1 IHC as a biomarker of ICI therapy and needs for further technical innovation to reproducibility.

Free Research Field

Pathology