胃と腸59巻11号

2024年11月発行

今月の主題 進行胃癌の診断と治療方針2024

主題

進行胃癌に対する病理診断・バイオマーカー検査

著者： 桑田健¹

所属機関： ¹国立がん研究センター東病院遺伝子診療部門

ページ範囲：P.1631 - P.1643

文献概要

要旨●進行胃癌に対する分子標的治療薬適応判定に必要な4つのバイオマーカーが存在する．いずれも患者の治療方針決定に直結する情報であり，日本胃癌学会は「切除不能進行・再発胃癌バイオマーカー検査の手引き」において，一次治療前にすべてのバイオマーカー検査の実施を推奨している．胃癌の病理診断に関わるすべての病理医は，これらバイオマーカー検査の意味を理解し，適切なタイミングで検査を実施できる体制を整える必要がある．あわせて，バイオマーカー検査で求められる病理組織検体の品質について，検体採取に関わる診療科を含めた施設内での情報共有も重要である．

参考文献

1）日本胃癌学会（編）．胃癌治療ガイドライン—医師用2021年7月改訂，第6版．金原出版，2021

2）Hudis CA. Trastuzumab-mechanism of action and use in clinical practice. N Engl J Med　357：39-51, 2007

3）Bang YJ, Van Cutsem E, Feyereislova A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer（ToGA）：a phase 3, open-label, randomised controlled trial. Lancet　376：687-697, 2010

4）Van Cutsem E, Bang YJ, Feng-Yi F, et al. HER2 screening data from ToGA：targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer　18：476-484, 2015

5）Oono Y, Kuwata T, Takashima K, et al. Clinicopathological features and endoscopic findings of HER2-positive gastric cancer. Surg Endosc　32：3964-3971, 2018

6）Matsusaka S, Nashimoto A, Nishikawa K, et al. Clinicopathological factors associated with HER2 status in gastric cancer：results from a prospective multicenter observational cohort study in a Japanese population（JFMC44-1101）. Gastric Cancer　19：839-851, 2016

7）Shitara K, Baba E, Fujitani K, et al. Discovery and development of trastuzumab deruxtecan and safety management for patients with HER2-positive gastric cancer. Gastric Cancer　24：780-789, 2021

8）Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med　382：2419-2430, 2020

9）de Ruiter EJ, Mulder FJ, Koomen BM, et al. Comparison of three PD-L1 immunohistochemical assays in head and neck squamous cell carcinoma（HNSCC）. Mod Pathol　34：1125-1132, 2021

10）Kulangara K, Zhang N, Corigliano E, et al. Clinical utility of the combined positive score for programmed death ligand-1 expression and the approval of pembrolizumab for treatment of gastric cancer. Arch Pathol Lab Med　143：330-337, 2019

11）Kang YK, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens（ONO-4538-12, ATTRACTION-2）：a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet　390：2461-2471, 2017

12）Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma（CheckMate 649）：a randomised, open-label, phase 3 trial. Lancet　398：27-40, 2021

13）Rha SY, Oh DY, Yanez P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer（KEYNOTE-859）：a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol　24：1181-1195, 2023

14）Narita Y, Sasaki E, Masuishi T, et al. PD-L1 immunohistochemistry comparison of 22C3 and 28-8 assays for gastric cancer. J Gastrointest Oncol　12：2696-2705, 2021

15）Ahn S, Kim KM. PD-L1 expression in gastric cancer：interchangeability of 22C3 and 28-8 pharmDx assays for responses to immunotherapy. Mod Pathol　34：1719-1727, 2021

16）Robert ME, Rüschoff J, Jasani B, et al. High interobserver variability among pathologists using combined positive score to evaluate PD-L1 expression in gastric, gastroesophageal junction, and esophageal adenocarcinoma. Mod Pathol　36：100154, 2023

17）Kim HD, Shin J, Song IH, et al. Discordant PD-L1 results between 28-8 and 22C3 assays are associated with outcomes of gastric cancer patients treated with nivolumab plus chemotherapy. Gastric Cancer　27：819-826, 2024

18）Klempner SJ, Cowden ES, Cytryn SL, et al. PD-L1 immunohistochemistry in gastric cancer：comparison of combined positive score and tumor area positivity across 28-8, 22C3, and SP263 assays. JCO Precis Oncol　8：e2400230, 2024

19）Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition：development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res　58：5248-5257, 1998

20）Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology　138：2073-2087, e2073, 2010

21）Guyot D'Asnieres De Salins A, Tachon G, Cohen R, et al. Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer. ESMO Open　6：100120, 2021

22）Leung SY, Yuen ST, Chung LP, et al. hMLH1 promoter methylation and lack of hMLH1 expression in sporadic gastric carcinomas with high-frequency microsatellite instability. Cancer Res　59：159-164, 1999

23）Akagi K, Oki E, Taniguchi H, et al. Real-world data on microsatellite instability status in various unresectable or metastatic solid tumors. Cancer Sci　112：1105-1113, 2021

24）Kawazoe A, Shitara K, Kuboki Y, et al. Clinicopathological features of 22C3 PD-L1 expression with mismatch repair, Epstein-Barr virus status, and cancer genome alterations in metastatic gastric cancer. Gastric Cancer　22：69-76, 2019

25）Maio M, Ascierto PA, Manzyuk L, et al. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers：updated analysis from the phase II KEYNOTE-158 study. Ann Oncol　33：929-938, 2022

26）Shitara K, Özgüroğlu M, Bang Y-J, et al. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer（KEYNOTE-061）：a randomised, open-label, controlled, phase 3 trial. Lancet　392：123-133, 2018

27）Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol　2：285-293, 2001

28）Tureci O, Koslowski M, Helftenbein G, et al. Claudin-18 gene structure, regulation, and expression is evolutionary conserved in mammals. Gene　481：83-92, 2011

29）Shitara K, Lordick F, Bang YJ, et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma（SPOTLIGHT）：a multicentre, randomised, double-blind, phase 3 trial. Lancet　401：1655-1668, 2023

30）Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma：the randomized, phase 3 GLOW trial. Nat Med　29：2133-2141, 2023

31）Nakayama I, Qi C, Chen Y, et al. Claudin 18.2 as a novel therapeutic target. Nat Rev Clin Oncol　21：354-369, 2024

32）Becker K, Mueller JD, Schulmacher C, et al. Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy. Cancer　98：1521-1530, 2003

33）Nakamura K, Kuwata T, Shimoda T, et al. Determination of the optimal cutoff percentage of residual tumors to define the pathological response rate for gastric cancer treated with preoperative therapy（JCOG1004-A）. Gastric Cancer　18：597-604, 2015

34）Nakamura Y, Sasaki A, Yukami H, et al. Emergence of concurrent multiple EGFR mutations and MET amplification in a patient with EGFR-amplified advanced gastric cancer treated with cetuximab. JCO Precis Oncol　4：1407-1413, 2020

35）Kotani D, Oki E, Nakamura Y, et al. Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer. Nat Med　29：127-134, 2023