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Annual Report 2021

Division of Molecular Pathology

Yasushi Yatabe, Nobuyoshi Hiraoka, Shigeki Sekine, Taisuke Mori, Yoshihisa Kobayashi, Yu Ohkubo, Takashi Teishikata, Taiki Hashimoto, Jumpei Kashima, Yuuki Nishimura, Masahiro Higashiyama, Yuji Muraoka, Noriteru Doi, Keiko Ishiyama, Reiko Ogawa, Chie Naito, Masanori Fuse, Eijitsu Ryo, Keiichiro Iwase, Asako Yoshida, Erika Kawasaki, Chika Takeuchi Richter, Harumi Koguchi, Sachiyo Hasegawa, Nozomi Handa

Introduction

Morphological analysis is one of the oldest fields in cancer research; thus, this field possesses a wide range of knowledge that has been developed over many decades. The Division of Molecular Pathology aims to integrate this knowledge into the rapidly developing field of molecular biology to study the molecular biological characteristics of tumors from the morphological perspective.

The Team and What We Do

Diagnosis is now made on the basis of various protein expressions and genetic abnormalities that go beyond morphology, and drugs that are highly effective against specific genetic mutations have been developed for some tumors. In the field of molecular pathology, we collaborate closely with the Department of Diagnostic Pathology at Central Hospital, and conduct research on the use of genetic alterations in diagnosis and the identification of genetic abnormalities that are useful in diagnosis, based on the questions raised in the process of diagnosis. We are also investigating the molecular mechanisms of tumorigenesis and progression based on the results of various biological research projects and cancer genome medicine.

Research activities

Lung cancer: In the discussion on the new TNM classification, it was proposed that tumors with grand glass opacity on CT images could be classified as a special cT category because of the difference in clinical outcome. In response, we examined whether they could be incorporated into the pT category. Our study found that it was difficult to correlate lepidic growth (corresponding to grand glass opacity on CT images) with pT, and thus, inclusion in the database for the 10th edition of the TNM was excluded. In addition, we became the first in the world to report false positive events in NGS and also found a way how to resolve them.

Gastrointestinal cancer: Based on an analysis of 144 duodenal adenomas and 54 adenocarcinomas, we proposed that while APC mutations are highly prevalent in adenomas, they are rare in adenocarcinomas, suggesting that most adenomas currently being resected clinically are lesions with a low risk of progressing to adenocarcinoma. We also identified KRAS or GNAS mutations in more than half of gastric ectopic gastric glands, demonstrating that these lesions, previously thought to be secondary changes associated with inflammation, are proliferative lesions with genetic mutations.

Head and neck cancer: The TP53 mutational status of 126 pairs of initial and recurrent head and neck squamous cell carcinoma tumor cases was analyzed. About one third of the recurrent cases showed a different TP53 status from the initial tumors. Survival after recurrence was related to the TP53 status of the recurrent tumor, which was useful for prognosis. Also, we developed a dedicated needle biopsy machine device for the head and neck region and reported on its usefulness in 88 cases of salivary gland tumors, including the positive diagnosis rate and complications.

Pancreatic cancer: Effective neoadjuvant chemotherapy (NAT) causes tissue remodeling of pancreatic cancer (PDAC) by altering the quality and quantity of collagen molecules, which are often involved in the malignant characteristics. This suggests that effective NAT changes the extracellular matrix by means of collagen profiles through the interaction between cancer-associated fibroblasts and cancer cells via Ephrin-A5 and EphA2 interaction.

Trans-organ approach: RAS family genes KRAS/NRAS/HRAS are most frequently mutated in cancer. We discovered an essential role of silent mutations in the oncogenic ability of KRAS Q61K and splicing vulnerability in KRAS/NRAS/HRAS Q61 mutant pan-cancers. A novel treatment targeting broad RAS Q61X mutant pan-cancers was developed.

Education

We accepted three graduated fellows and trained them for cancer research.

Future Prospects

With advances in basic research and the spread of cancer genome medicine, fundamental genetic disorders have been discussed in clinical settings. Our research aim is to use our morphological approach as a means of assigning biological meaning/significance to individual diseases and obtaining background molecular features across the organs.

List of papers published in 2021

Journal

1. Cheung CC, Smith AC, Albadine R, Bigras G, Bojarski A, Couture C, Cutz JC, Huang WY, Ionescu D, Itani D, Izevbaye I, Karsan A, Kelly MM, Knoll J, Kwan K, Nasr MR, Qing G, Rashid-Kolvear F, Sekhon HS, Spatz A, Stockley T, Tran-Thanh D, Tucker T, Waghray R, Wang H, Xu Z, Yatabe Y, Torlakovic EE, Tsao MS. Canadian ROS proto-oncogene 1 study (CROS) for multi-institutional implementation of ROS1 testing in non-small cell lung cancer. Lung Cancer 2021; 160: 127-135. https://doi.org/10.1016/j.lungcan.2021.08.003

2. Hamada A, Soh J, Hata A, Nakamatsu K, Shimokawa M, Yatabe Y, Oizumi H, Tsuboi M, Horinouchi H, Yoshino I, Tanahashi M, Toyooka S, Okada M, Yokomise H, Yamashita M, Nishimura Y, Yamamoto N, Nakagawa K, Mitsudomi T. Phase II Study of Neoadjuvant Concurrent Chemo-immuno-radiation Therapy Followed by Surgery and Adjuvant Immunotherapy for Resectable Stage IIIA-B (Discrete N2) Non-small-cell Lung Cancer: SQUAT trial (WJOG 12119L). Clin Lung Cancer 2021; 22: 596-600. https://doi.org/10.1016/j.cllc.2021.04.006

3. Hasegawa Y, Tsukahara K, Yoshimoto S, Miura K, Yokoyama J, Hirano S, Uemura H, Sugasawa M, Yoshizaki T, Homma A, Chikamatsu K, Suzuki M, Shiotani A, Matsuzuka T, Kohno N, Miyazaki M, Oze I, Matsuo K, Kosuda S, Yatabe Y. Reply to P. Kaul et al. J Clin Oncol 2021; 39: 3518-3519. https://doi.org/10.1200/JCO.21.01554

4. Hasegawa Y, Tsukahara K, Yoshimoto S, Miura K, Yokoyama J, Hirano S, Uemura H, Sugasawa M, Yoshizaki T, Homma A, Chikamatsu K, Suzuki M, Shiotani A, Matsuzuka T, Kohno N, Miyazaki M, Oze I, Matsuo K, Kosuda S, Yatabe Y, Group HR. Neck Dissections Based on Sentinel Lymph Node Navigation Versus Elective Neck Dissections in Early Oral Cancers: A Randomized, Multicenter, and Noninferiority Trial. J Clin Oncol 2021; 39: 2025-2036. https://doi.org/10.1200/JCO.20.03637

5. Ikegami M, Kohsaka S, Hirose T, Ueno T, Inoue S, Kanomata N, Yamauchi H, Mori T, Sekine S, Inamoto Y, Yatabe Y, Kobayashi H, Tanaka S, Mano H. MicroSEC filters sequence errors for formalin-fixed and paraffin-embedded samples. Commun Biol 2021; 4: 1396. https://doi.org/10.1038/s42003-021-02930-4

6. Ishizu K, Hashimoto T, Naka T, Yatabe Y, Kojima M, Kuwata T, Nonaka S, Oda I, Esaki M, Kudo M, Gotohda N, Yoshida T, Yoshikawa T, Sekine S. APC mutations are common in adenomas but infrequent in adenocarcinomas of the non-ampullary duodenum. J Gastroenterol 2021; 56: 988-998. https://doi.org/10.1007/s00535-021-01823-x

7. Karigane D, Kasahara H, Shiroshita K, Fujita S, Kobayashi H, Tamaki S, Yamazaki R, Yahagi K, Yatabe Y, Kondoh N, Arai T, Katagiri H, Shimizu N, Sakurai M, Kikuchi T, Kato J, Shimizu T, Hayakawa T, Yaguchi T, Matsushita M, Nakajima H, Kawakami Y, Murata M, Mori T, Sasaki T, Okamoto S, Takubo K. Detection of residual disease in chronic myeloid leukemia utilizing genomic next generation sequencing reveals persistence of differentiated Ph(+) B cells but not bone marrow stem/progenitors. Leuk Lymphoma 2021; 62: 679-687. https://doi.org/10.1080/10428194.2020.1837366

8. Kobayashi K, Yoshimoto S, Ando M, Matsumoto F, Murakami N, Omura G, Honma Y, Matsumoto Y, Ikeda A, Sakai A, Eguchi K, Ito A, Ryo E, Yatabe Y, Mori T. Full-coverage TP53 deep sequencing of recurrent head and neck squamous cell carcinoma facilitates prognostic assessment after recurrence. Oral Oncol 2021; 113: 105091. https://doi.org/10.1016/j.oraloncology.2020.105091

9. Kuroda H, Masago K, Takahashi Y, Fujita S, Sasaki E, Nakada T, Sakakura N, Nakanishi H, Matsushita H, Yatabe Y. Positive Correlation Between the Number of Circulating Tumor Cells in the Pulmonary Vein and Tumor Spread Through Air Spaces in Resected Non-small Cell Lung Cancer. Anticancer Res 2021; 41: 5499-5505. https://doi.org/10.21873/anticanres.15363

10. Matsui T, Sakakura N, Koyama S, Nakanishi K, Sasaki E, Kato S, Hosoda W, Murakami Y, Kuroda H, Yatabe Y. Comparison of Surgical Outcomes Between Invasive Mucinous and Non-Mucinous Lung Adenocarcinoma. Ann Thorac Surg 2021; 112: 1118-1126. https://doi.org/10.1016/j.athoracsur.2020.09.042

11. Mino-Kenudson M, Le Stang N, Daigneault JB, Nicholson AG, Cooper WA, Roden AC, Moreira AL, Thunnissen E, Papotti M, Pelosi G, Motoi N, Poleri C, Brambilla E, Redman M, Jain D, Dacic S, Yatabe Y, Tsao MS, Lopez-Rios F, Botling J, Chen G, Chou TY, Hirsch FR, Beasley MB, Borczuk A, Bubendorf L, Chung JH, Hwang D, Lin D, Longshore J, Noguchi M, Rekhtman N, Sholl L, Travis W, Yoshida A, Wynes MW, Wistuba, II, Kerr KM, Lantuejoul S. The International Association for the Study of Lung Cancer Global Survey on Programmed Death-Ligand 1 Testing for NSCLC. J Thorac Oncol 2021; 16: 686-696. https://doi.org/10.1016/j.jtho.2020.12.026

12. Mizuno T, Yoshida T, Sunami K, Koyama T, Okita N, Kubo T, Sudo K, Shimoi T, Ueno H, Saito E, Katanoda K, Shibata T, Yonemori K, Okusaka T, Boku N, Ohe Y, Hiroshima Y, Ueno M, Kuboki Y, Doi T, Nakamura K, Kohno T, Yatabe Y, Yamamoto N. Study protocol for NCCH1908 (UPFRONT-trial): a prospective clinical trial to evaluate the feasibility and utility of comprehensive genomic profiling prior to the initial systemic treatment in advanced solid tumour patients. Jpn J Clin Oncol 2021; 51: 1757-1760. https://doi.org/10.1093/jjco/hyab159

13. Morita C, Yoshida T, Shirasawa M, Masuda K, Matsumoto Y, Shinno Y, Yagishita S, Okuma Y, Goto Y, Horinouchi H, Yamamoto N, Motoi N, Yatabe Y, Ohe Y. Clinical characteristics of advanced non-small cell lung cancer patients with EGFR exon 20 insertions. Sci Rep 2021; 11: 18762. https://doi.org/10.1038/s41598-021-98275-3

14. Muto Y, Ryo E, Namikawa K, Takahashi A, Ogata D, Fujimura T, Yatabe Y, Aiba S, Yamazaki N, Mori T. RB1 gene mutations are a distinct predictive factor in Merkel cell carcinoma. Pathol Int 2021; 71: 337-347. https://doi.org/10.1111/pin.13090

15. Narita Y, Sasaki E, Masuishi T, Taniguchi H, Kadowaki S, Ito S, Yatabe Y, Muro K. PD-L1 immunohistochemistry comparison of 22C3 and 28-8 assays for gastric cancer. J Gastrointest Oncol 2021; 12: 2696-2705. https://doi.org/10.21037/jgo-21-505

16. Nishimura Y, Ryo E, Yamazaki N, Yatabe Y, Mori T. Cutaneous Primary NUT Carcinoma With BRD3-NUTM1 Fusion. Am J Surg Pathol 2021; 45: 1582-1584. https://doi.org/10.1097/PAS.0000000000001801

17. Okuma HS, Yonemori K, Kojima Y, Tanioka M, Sudo K, Noguchi E, Hijioka S, Wakakuwa K, Kato K, Hirakawa A, Kuchiba A, Kubo T, Ichikawa H, Yoshida A, Yatabe Y, Nakamura K, Mano H, Yamamoto N, Fujiwara Y. Clinical Utility of Circulating Tumor DNA in Advanced Rare Cancers. Front Oncol 2021; 11: 732525. https://doi.org/10.3389/fonc.2021.732525

18. Sakao Y, Kuroda H, Saito Y, Yamauchi Y, Yokote F, Kawamura M, Yatabe Y. Radiological imaging and pathological findings of small lung adenocarcinoma: a narrative review. J Thorac Dis 2021; 13: 366-371. https://doi.org/10.21037/jtd-20-844

19. Sakuma K, Sasaki E, Hosoda W, Komori K, Shimizu Y, Yatabe Y, Aoki M. MYB mediates downregulation of the colorectal cancer metastasis suppressor heterogeneous nuclear ribonucleoprotein L-like during epithelial-mesenchymal transition. Cancer Sci 2021; 112: 3846-3855. https://doi.org/10.1111/cas.15069

20. Satoh H, Okuma Y, Kashima J, Konnno-Yamamoto A, Yatabe Y, Ohe Y. Alectinib for Miliary Lung Metastasis in ALK-Positive Lung Adenocarcinoma. Onco Targets Ther 2021; 14: 2911-2915. https://doi.org/10.2147/OTT.S300229

21. Shibayama T, Makise N, Motoi T, Mori T, Hiraoka N, Yonemori K, Watanabe SI, Esaki M, Morizane C, Okuma T, Kawai A, Ushiku T, Yatabe Y, Yoshida A. Clinicopathologic Characterization of Epithelioid Hemangioendothelioma in a Series of 62 Cases: A Proposal of Risk Stratification and Identification of a Synaptophysin-positive Aggressive Subset. Am J Surg Pathol 2021; 45: 616-626. https://doi.org/10.1097/PAS.0000000000001660

22. Shimoda Y, Yoshida T, Shirasawa M, Mizuno T, Jo H, Matsumoto Y, Shinno Y, Okuma Y, Goto Y, Horinouchi H, Yamamoto N, Yatabe Y, Ohe Y, Motoi N. Smoking History Predicts High Presence of TILs and Efficacy of PD-1 Blockade in PD-L1 Expression-negative Non-small Cell Lung Cancer Patients. Anticancer Res 2021; 41: 5739-5747. https://doi.org/10.21873/anticanres.15390

23. Sugawara H, Watanabe H, Kunimatsu A, Abe O, Watanabe SI, Yatabe Y, Kusumoto M. Adenocarcinoma in situ and minimally invasive adenocarcinoma in lungs of smokers: image feature differences from those in lungs of non-smokers. BMC Med Imaging 2021; 21: 172. https://doi.org/10.1186/s12880-021-00705-1

24. Sugawara S, Sone M, Itou C, Kimura S, Kusumoto M, Kato T, Yonemori K, Yatabe Y, Arai Y. Analysis of factors affecting the diagnostic yield of image-guided percutaneous core needle biopsy for peritoneal/omental lesions. Abdom Radiol (NY) 2021; 46: 4499-4508. https://doi.org/10.1007/s00261-021-03088-7

25. Sunami K, Bando H, Yatabe Y, Naito Y, Takahashi H, Tsuchihara K, Toyooka S, Mimori K, Kohsaka S, Uetake H, Kinoshita I, Komine K, Takeda M, Hayashida T, Tamura K, Nishio K, Yamamoto N, Working Group of a Joint Task Force of Three Academic Societies for the Promotion of Cancer Genomic M. Appropriate use of cancer comprehensive genome profiling assay using circulating tumor DNA. Cancer Sci 2021; 112: 3911-3917. https://doi.org/10.1111/cas.15022

26. Suzuki M, Yagishita S, Sugihara K, Ogitani Y, Nishikawa T, Ohuchi M, Teishikata T, Jikoh T, Yatabe Y, Yonemori K, Tamura K, Hasegawa K, Hamada A. Visualization of Intratumor Pharmacokinetics of [fam-] Trastuzumab Deruxtecan (DS-8201a) in HER2 Heterogeneous Model Using Phosphor-integrated Dots Imaging Analysis. Clin Cancer Res 2021; 27: 3970-3979. https://doi.org/10.1158/1078-0432.CCR-21-0397

27. Suzuki M, Matsumoto Y, Imabayashi T, Teishikata T, Tsuchida T, Asamura H, Yatabe Y. Cryobiopsy as a reliable technique for the preoperative identification of micropapillary/solid components in early-stage lung adenocarcinoma. Lung Cancer 2021; 162: 147-153. https://doi.org/10.1016/j.lungcan.2021.11.004

28. Takeyasu Y, Yoshida T, Motoi N, Teishikata T, Tanaka M, Matsumoto Y, Shinno Y, Okuma Y, Goto Y, Horinouchi H, Kakishima H, Tsuchida T, Yamamoto N, Ohe Y, Yatabe Y. Feasibility of next-generation sequencing (Oncomine DX Target Test) for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients. Jpn J Clin Oncol 2021; 51: 1114-1122. https://doi.org/10.1093/jjco/hyab059

29. Takeyasu Y, Yoshida T, Motoi N, Teishikata T, Tanaka M, Matsumoto Y, Shinno Y, Okuma Y, Goto Y, Horinouchi H, Kakishima H, Tsuchida T, Yamamoto N, Ohe Y, Yatabe Y. Corrigendum to: Feasibility of next-generation sequencing (Oncomine DX Target Test) for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients. Jpn J Clin Oncol 2021; 51: 1183. https://doi.org/10.1093/jjco/hyab092

30. Tanaka Y, Chiwaki F, Kojima S, Kawazu M, Komatsu M, Ueno T, Inoue S, Sekine S, Matsusaki K, Matsushita H, Boku N, Kanai Y, Yatabe Y, Sasaki H, Mano H. Multi-omic profiling of peritoneal metastases in gastric cancer identifies molecular subtypes and therapeutic vulnerabilities. Nat Cancer 2021; 2: 962-977. https://doi.org/10.1038/s43018-021-00240-6

31. Teishikata T, Shiraishi K, Shinno Y, Kobayashi Y, Kashima J, Ishiyama T, Yoshida T, Mori T, Yatabe Y. An Alert to Possible False Positives With a Commercial Assay for MET Exon 14 Skipping. J Thorac Oncol 2021; 16: 2133-2138. https://doi.org/10.1016/j.jtho.2021.07.028

32. Tsuboi M, Weder W, Escriu C, Blakely C, He J, Dacic S, Yatabe Y, Zeng L, Walding A, Chaft JE. Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for EGFR-mutated resectable non-small-cell lung cancer: NeoADAURA. Future Oncol 2021; 17: 4045-4055. https://doi.org/10.2217/fon-2021-0549

33. Yagishita S, Kato K, Takahashi M, Imai T, Yatabe Y, Kuwata T, Suzuki M, Ochiai A, Ohtsu A, Shimada K, Nishida T, Hamada A, Mano H. Characterization of the large-scale Japanese patient-derived xenograft (J-PDX) library. Cancer Sci 2021; 112: 2454-2466. https://doi.org/10.1111/cas.14899

34. Yatabe Y, Yoshiki Y, Matsumura K, Togo K, Kikkawa H, Iadeluca L, Li B, Nishio K. Real-World Evidence of Diagnostic Testing for Driver Oncogene Mutations in Lung Cancer in Japan. JTO Clin Res Rep 2021; 2: 100136. https://doi.org/10.1016/j.jtocrr.2020.100136

35. Yonemaru J, Hashimoto T, Takayanagi D, Naka T, Yatabe Y, Kanemitsu Y, Shiraishi K, Sekine S. NTRK fusion-positive colorectal cancer in Japanese population. Pathol Int 2021; 71: 355-359. https://doi.org/10.1111/pin.13082

36. Yoshida A, Hashimoto T, Ryo E, Yoshida KI, Motoi T, Yatabe Y, Mori T. Confirmation of NKX3-1 Expression in EWSR1-NFATC2 Sarcoma and Mesenchymal Chondrosarcoma Using Monoclonal Antibody Immunohistochemistry, RT-PCR, and RNA In Situ Hybridization. Am J Surg Pathol 2021; 45: 578-582. https://doi.org/10.1097/PAS.0000000000001627

37. Yotsukura M, Asamura H, Motoi N, Kashima J, Yoshida Y, Nakagawa K, Shiraishi K, Kohno T, Yatabe Y, Watanabe SI. Long-Term Prognosis of Patients With Resected Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma of the Lung. J Thorac Oncol 2021; 16: 1312-1320. https://doi.org/10.1016/j.jtho.2021.04.007

38. Cho H, Hashimoto T, Naka T, Yatabe Y, Oda I, Saito Y, Yoshikawa T, Sekine S. Activating KRAS and GNAS mutations in heterotopic submucosal glands of the stomach. J Gastroenterol 2022; 57: 333-343. https://doi.org/10.1007/s00535-022-01863-x

39. Fujikawa R, Muraoka Y, Kashima J, Yoshida Y, Ito K, Watanabe H, Kusumoto M, Watanabe SI, Yatabe Y. Clinicopathologic and Genotypic Features of Lung Adenocarcinoma Characterized by the International Association for the Study of Lung Cancer Grading System. J Thorac Oncol 2022; 17: 700-707. https://doi.org/10.1016/j.jtho.2022.02.005

40. Horinouchi H, Kusumoto M, Yatabe Y, Aokage K, Watanabe SI, Ishikura S. Lung Cancer in Japan. J Thorac Oncol 2022; 17: 353-361. https://doi.org/10.1016/j.jtho.2021.11.020

41. Jain D, Nambirajan A, Chen G, Geisinger K, Hiroshima K, Layfield L, Minami Y, Moreira AL, Motoi N, Papotti M, Rekhtman N, Russell PA, Prince SS, Schmitt F, Yatabe Y, Eppenberger-Castori S, Bubendorf L, Committee IP. Non-small cell lung carcinoma subtyping in conventional cytology: Results of the IASLC Cytology Working Group survey to determine specific cytomorphological criteria for adenocarcinoma and squamous cell carcinoma. J Thorac Oncol 2022. https://doi.org/10.1016/j.jtho.2022.02.013

42. Jo H, Yagishita S, Hayashi Y, Ryu S, Suzuki M, Kohsaka S, Ueno T, Matsumoto Y, Horinouchi H, Ohe Y, Watanabe SI, Motoi N, Yatabe Y, Mano H, Takahashi K, Hamada A. Comparative Study on the Efficacy and Exposure of Molecular Target Agents in Non-small Cell Lung Cancer PDX Models with Driver Genetic Alterations. Mol Cancer Ther 2022; 21: 359-370. https://doi.org/10.1158/1535-7163.MCT-21-0371

43. Kawakubo N, Okubo Y, Yotsukura M, Yoshida Y, Nakagawa K, Yonemori K, Watanabe H, Yatabe Y, Watanabe SI. Assessment of Resectability of Mediastinal Germ Cell Tumor Using Preoperative Computed Tomography. J Surg Res 2022; 272: 61-68. https://doi.org/10.1016/j.jss.2021.11.002

44. Kojima N, Komiyama M, Shinoda Y, Watanabe SI, Yatabe Y, Kawai A, Yoshida A. Liposarcoma With Hibernoma-like Histology: A Clinicopathologic Study of 16 Cases. Am J Surg Pathol 2022. https://doi.org/10.1097/PAS.0000000000001911

45. Kojima N, Arai Y, Satomi K, Kubo T, Matsushita Y, Mori T, Matsushita H, Ushijima T, Yatabe Y, Shibata T, Yonemori K, Ichimura K, Ichikawa H, Kawai A, Yoshida A. Co-expression of ERG and CD31 in a subset of CIC-rearranged sarcoma: a potential diagnostic pitfall. Mod Pathol 2022. https://doi.org/10.1038/s41379-022-01078-8

46. Kumagai S, Koyama S, Itahashi K, Tanegashima T, Lin YT, Togashi Y, Kamada T, Irie T, Okumura G, Kono H, Ito D, Fujii R, Watanabe S, Sai A, Fukuoka S, Sugiyama E, Watanabe G, Owari T, Nishinakamura H, Sugiyama D, Maeda Y, Kawazoe A, Yukami H, Chida K, Ohara Y, Yoshida T, Shinno Y, Takeyasu Y, Shirasawa M, Nakama K, Aokage K, Suzuki J, Ishii G, Kuwata T, Sakamoto N, Kawazu M, Ueno T, Mori T, Yamazaki N, Tsuboi M, Yatabe Y, Kinoshita T, Doi T, Shitara K, Mano H, Nishikawa H. Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments. Cancer Cell 2022; 40: 201-218 e209. https://doi.org/10.1016/j.ccell.2022.01.001

47. Maekawa M, Taniguchi T, Nishio K, Sakai K, Matsushita K, Nakatani K, Ishige T, Ikejiri M, Nishihara H, Sunami K, Yatabe Y, Hatanaka KC, Hatanaka Y, Yamamoto Y, Fukuyama K, Oda S, Saito K, Yokomura M, Kubo Y, Sato H, Tanaka Y, Fuchioka M, Yamasaki T, Matsuda K, Kurachi K, Funai K, Baba S, Iwaizumi M. Precision cancer genome testing needs proficiency testing involving all stakeholders. Sci Rep 2022; 12: 1494. https://doi.org/10.1038/s41598-022-05589-x

48. Muraoka Y, Yoshida Y, Nakagawa K, Ito K, Watanabe H, Narita T, Watanabe SI, Tsukiji Lung Cancer Working G, Yotsukura M, Motoi N, Yatabe Y. Maximum standardized uptake value of the primary tumor does not improve candidate selection for sublobar resection. J Thorac Cardiovasc Surg 2022; 163: 1656-1665 e1653. https://doi.org/10.1016/j.jtcvs.2021.06.053

49. Nicholson AG, Tsao MS, Beasley MB, Borczuk AC, Brambilla E, Cooper WA, Dacic S, Jain D, Kerr KM, Lantuejoul S, Noguchi M, Papotti M, Rekhtman N, Scagliotti G, van Schil P, Sholl L, Yatabe Y, Yoshida A, Travis WD. The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015. J Thorac Oncol 2022; 17: 362-387. https://doi.org/10.1016/j.jtho.2021.11.003

50. Noguchi R, Yoshimatsu Y, Ono T, Sei A, Motoi N, Yatabe Y, Yoshida Y, Watanabe S, Kondo T. Establishment and characterization of NCC-DMM1-C1, a novel patient-derived cell line of desmoplastic malignant pleural mesothelioma. Oncol Lett 2022; 23: 64. https://doi.org/10.3892/ol.2021.13182

51. Okubo Y, Kashima J, Teishikata T, Muraoka Y, Yotsukura M, Yoshida Y, Nakagawa K, Watanabe H, Kusumoto M, Watanabe SI, Yatabe Y. Prognostic Impact of the Histologic Lepidic Component in Pathologic Stage IA Adenocarcinoma. J Thorac Oncol 2022; 17: 67-75. https://doi.org/10.1016/j.jtho.2021.09.006

52. Passaro A, Leighl N, Blackhall F, Popat S, Kerr K, Ahn MJ, Arcila ME, Arrieta O, Planchard D, de Marinis F, Dingemans AM, Dziadziuszko R, Faivre-Finn C, Feldman J, Felip E, Curigliano G, Herbst R, Janne PA, John T, Mitsudomi T, Mok T, Normanno N, Paz-Ares L, Ramalingam S, Sequist L, Vansteenkiste J, Wistuba, II, Wolf J, Wu YL, Yang SR, Yang JCH, Yatabe Y, Pentheroudakis G, Peters S. ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer. Ann Oncol 2022; 33: 466-487. https://doi.org/10.1016/j.annonc.2022.02.003

53. Shibayama T, Shimoi T, Mori T, Noguchi E, Honma Y, Hijioka S, Yoshida M, Ogawa C, Yonemori K, Yatabe Y, Yoshida A. Cytokeratin-positive Malignant Tumor in the Abdomen With EWSR1/FUS-CREB Fusion: A Clinicopathologic Study of 8 Cases. Am J Surg Pathol 2022; 46: 134-146. https://doi.org/10.1097/PAS.0000000000001742

54. So C, Yoshida T, Mizuno T, Yatabe Y, Ohe Y. Rapidly progressing metastatic malignant melanoma mimicking primary pleural tumor: A case report. Thorac Cancer 2022; 13: 1423-1426. https://doi.org/10.1111/1759-7714.14392

55. Sone M, Sugawara S, Yatabe Y. Role of Image-Guided Percutaneous Needle Biopsy in the Age of Precision Medicine. Curr Oncol Rep 2022. https://doi.org/10.1007/s11912-022-01271-7

56. Sugawara H, Watanabe H, Kunimatsu A, Abe O, Yatabe Y, Watanabe SI, Kusumoto M. Tumor size in patients with severe pulmonary emphysema might be underestimated on preoperative CT. Eur Radiol 2022; 32: 163-173. https://doi.org/10.1007/s00330-021-08105-3

57. Sugawara H, Ito K, Watanabe H, Morita T, Yatabe Y, Watanabe SI, Kusumoto M. Clinical usefulness of PET/MRI in differentiating anterior mediastinal masses. Nucl Med Commun 2022; 43: 92-99. https://doi.org/10.1097/MNM.0000000000001483

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