Annual Report 2023
Department of Pathology and Clinical Laboratories
Genichiro Ishii, Michiko Nagamine, Tetsuro Taki, Saori Miyazaki, Motohiro Kojima, Shingo Sakashita, Naoya Sakamoto, Takeshi Kuwata, Shohei Murata, Masahiro Adachi, Yukiko Sasahara, Hirohiko Miyake, Yuko Miyakami, Satoshi Fumimoto, Satoshi Fujii, Reiko Watanabe, Hiroki Imada, Hiroko Hashimoto, Aya Endo, Misato Ohhashi, Yuduri Hasegawa, Yumiko Follett
Introduction
The Department of Pathology and Clinical Laboratories (DPCL) conducts routine hospital services and support research activities based on the requirements of both College of American Pathologists (CAP) and ISO15189. The number of samples examined in 2023 is listed in Table 1. We conducted the following pathological diagnoses this year: 14,258 biopsy specimens, 3,526 intraoperative tissue specimens, 5,846 cytology specimens, and 5 autopsy cases.
Clinicopathological conferences are held regularly with each clinical department/section.
Staff members participate in expert panel meetings to medically interpret the results of cancer gene panel tests.
Table 1. Number of pathology and cytology samples examined in the Department of Pathology in 2023
The Team and What We Do
1) Clinical pathology conferences (CPC) with each department are held regularly to stimulate medical/research activities.
2) Some staff members also work at the EPOC, where they are engaged in research aimed at establishing new diagnostic methods, clarifying the nature of cancer, and developing new treatment methods using in vitro experimental systems in addition to clinicopathological studies.
3) As part of the biobank project, we are contributing to research activities by storing plasma, DNA/RNA of peripheral blood mononuclear cells, and cryopreservation of surgical specimens.
4) In support of the TITANIA study and SCRUM study, we are cooperating in the collection of specimens.
Research Activities
The following are this year's major research results.
1. We showed that NETosis and systemic inflammation are associated with dirty necrosis in renal cell carcinoma.
2. The grading system in lung biopsy tissue was shown to reflect the grading system in surgical tissue to some extent.
3. We found the number of macrophages infiltrating around lung adenocarcinoma as a prognostic factor and examined their gene expression.
4. We analyzed the relationship between physical hardness and immune microenvironment in preoperatively treated pancreatic cancer.
5. A multicenter retrospective study of 1202 colorectal cancer cases from 6 centers was conducted to evaluate the prognostic utility of elastic lamina invasion.
6. Sarcomatoid carcinoma (SC) is a rare disease that can occur in any organ. To identify common features of SCs across organs, we evaluated clinicopathologic and immunologic characteristics of SCs defined by a single histologic criterion across organs compared with stage-adjusted, randomly matched conventional cancers (non-SC).
7. Peritumoral macrophage counts (pAMs) are a prognostic factor for lung NEC, suggesting that pAMs may contribute to tumor progression within the peritumoral microenvironment.
8. We are the first to report that non-acinar and non-lepidic subtypes are predictors of recurrence in pathologic stage II-III EGFR mutation-positive lung adenocarcinoma and have a high-grade tumor microenvironment.
Clinical Trials
Pathological testing strengthens the quality control and quality assurance of clinical tests performed in the NCCHE's clinical trials.
Education
1) Meetings are held regularly with residents (once a week), and hypotheses inspired by Clinical Question (CQ) are developed into papers.
2) Our staff members directly instruct pathology residents and clinical residents on diagnostic training and pathology research. Weekly case review meetings or research presentations are held to teach presentation skills.
3) Some of the staff members have supervised master's students as faculty members of the Graduate School of Frontier Sciences at the University of Tokyo.
Future Prospects
1) Aim to improve diagnostic accuracy by maintaining CAP accreditation.
2) Actively develop LDT and introduce new diagnostic methods, aiming to develop new diagnostic methods that meet the “patient first” philosophy.
3) Further promote translational research using pathological specimens.
List of papers published in 2023
Journal
1. Nomura K, Aokage K, Kaminuma Y, Nakai T, Wakabayashi M, Ikeno T, Koike Y, Taki T, Miyoshi T, Tane K, Samejima J, Ishii G, Tsuboi M. EGFR mutation impacts recurrence in high-risk early-stage lung adenocarcinoma in the IASLC grading system. International journal of clinical oncology, 29:248-257, 2024
2. Takei S, Tanaka Y, Lin YT, Koyama S, Fukuoka S, Hara H, Nakamura Y, Kuboki Y, Kotani D, Kojima T, Bando H, Mishima S, Ueno T, Kojima S, Wakabayashi M, Sakamoto N, Kojima M, Kuwata T, Yoshino T, Nishikawa H, Mano H, Endo I, Shitara K, Kawazoe A. Multiomic molecular characterization of the response to combination immunotherapy in MSS/pMMR metastatic colorectal cancer. Journal for immunotherapy of cancer, 12:e008210, 2024
3. Minamide T, Ikematsu H, Kajiwara Y, Oka S, Ajioka Y, Ueno H. Impact of Lesion Location on Recurrence After Resection of T1 Colorectal Cancer: Post Hoc Analysis of a Nationwide Multicenter Cohort Study. Gastroenterology, 166:198-201.e3, 2024
4. Odate T, Satomi K, Kubo T, Matsushita Y, Ueno T, Kurose A, Shomori K, Nakai T, Watanabe R, Segawa K, Ohshika S, Miyake N, Kudo S, Shimoi T, Kobayashi E, Komiyama M, Yoshimoto S, Nakatani F, Kawai A, Yatabe Y, Kohsaka S, Ichimura K, Ichikawa H, Yoshida A. Inflammatory Rhabdomyoblastic Tumor: Clinicopathologic and Molecular Analysis of 13 Cases. Modern pathology, 37:100359, 2024
5. Hiyama T, Miyasaka Y, Kuno H, Sekiya K, Sakashita S, Shinozaki T, Kobayashi T. Posttreatment Head and Neck Cancer Imaging: Anatomic Considerations Based on Cancer Subsites. Radiographics, 44:e230099, 2024
6. Tabata S, Umemura S, Narita M, Udagawa H, Ishikawa T, Tsuboi M, Goto K, Ishii G, Tsuchihara K, Ochiai A, Kobayashi SS, Soga T, Makinoshima H. Metabolic Hallmarks for Purine Nucleotide Biosynthesis in Small Cell Lung Carcinoma. Molecular cancer research, 22:82-93, 2024
7. Kitagawa S, Zenke Y, Taki T, Aokage K, Sakai T, Shibata Y, Izumi H, Nosaki K, Umemura S, Matsumoto S, Yoh K, Sakamoto N, Sakashita S, Kojima M, Tsuboi M, Goto K, Ishii G. Prognostic value of predominant subtype in pathological stage II-III lung adenocarcinoma with epidermal growth factor receptor mutation. Lung cancer (Amsterdam, Netherlands), 188:107453, 2024
8. Qin Z, Yue M, Tang S, Wu F, Sun H, Li Y, Zhang Y, Izumi H, Huang H, Wang W, Xue Y, Tong X, Mori S, Taki T, Goto K, Jin Y, Li F, Li FM, Gao Y, Fang Z, Fang Y, Hu L, Yan X, Xu G, Chen H, Kobayashi SS, Ventura A, Wong KK, Zhu X, Chen L, Ren S, Chen LN, Ji H. EML4-ALK fusions drive lung adeno-to-squamous transition through JAK-STAT activation. The Journal of experimental medicine, 221:e20232028, 2024
9. Okunaka M, Kotani D, Fujiwara H, Sato K, Fujiwara N, Mishima S, Sakashita S, Yoshino T, Fujita T, Kojima T. Prognosis of patients with residual pathological disease after neoadjuvant docetaxel, cisplatin, and 5-fluorouracil therapy and surgery for esophageal squamous cell carcinoma: a retrospective cohort study. Therapeutic advances in medical oncology, 16:17588359241229432, 2024
10. Kagoura M, Kobayashi S, Kojima M, Kudo M, Sugimoto M, Konishi M, Gotohda N. Survival outcome of patient with pT1N0 biliary tract cancer treated with surgery alone. European journal of surgical oncology, 50:107980, 2024
11. Sasaki T, Kuno H, Hiyama T, Oda S, Masuoka S, Miyasaka Y, Taki T, Nagasaki Y, Ohtani-Kim SJ, Ishii G, Kaku S, Shroff GS, Kobayashi T. 2021 WHO Classification of Lung Cancer: Molecular Biology Research and Radiologic-Pathologic Correlation. Radiographics, 44:e230136, 2024
12. Oka S, Tanaka S, Kajiwara Y, Saito S, Fukunaga Y, Takamatsu M, Kawachi H, Hotta K, Ikematsu H, Kojima M, Saito Y, Yamada M, Kanemitsu Y, Sekine S, Nagata S, Yamada K, Kobayashi N, Ishihara S, Saitoh Y, Matsuda K, Togashi K, Komori K, Ishiguro M, Kuwai T, Okuyama T, Ohuchi A, Ohnuma S, Sakamoto K, Sugai T, Katsumata K, Matsushita HO, Yamano HO, Eda H, Uraoka T, Akimoto N, Kobayashi H, Sugihara K, Ueno H. Treatment Decision for Locally Resected T1 Colorectal Carcinoma-Verification of the Japanese Guideline Criteria for Additional Surgery Based on Long-Term Clinical Outcomes. The American journal of gastroenterology, 2024
13. Adachi M, Taki T, Sakamoto N, Kojima M, Hirao A, Matsuura K, Hayashi R, Tabuchi K, Ishikawa S, Ishii G, Sakashita S. Extracting interpretable features for pathologists using weakly supervised learning to predict p16 expression in oropharyngeal cancer. Scientific reports, 14:4506, 2024
14. Nagasaki Y, Taki T, Nomura K, Tane K, Miyoshi T, Samejima J, Aokage K, Ohtani-Kim SJ, Kojima M, Sakashita S, Sakamoto N, Ishikawa S, Suzuki K, Tsuboi M, Ishii G. Spatial intratumor heterogeneity of programmed death-ligand 1 expression predicts poor prognosis in resected non-small cell lung cancer. Journal of the National Cancer Institute, djae053, 2024
15. Shirane Y, Fujii Y, Ono A, Nakahara H, Hayes CN, Miura R, Murakami S, Sakamoto N, Uchikawa S, Fujino H, Nakahara T, Murakami E, Yamauchi M, Miki D, Kawaoka T, Arihiro K, Tsuge M, Oka S. Peripheral T Cell Subpopulations as a Potential Surrogate Biomarker during Atezolizumab plus Bevacizumab Treatment for Hepatocellular Carcinoma. Cancers, 16:1328, 2024
16. Minakata N, Sakashita S, Wakabayashi M, Nakamura Y, Sunakawa H, Yoda Y, Ishii G, Yano T. Immunohistochemistry and oxygen saturation endoscopic imaging reveal hypoxia in submucosal invasive esophageal squamous cell carcinoma. Cancer medicine, 12:15809-15819, 2023
17. Kajiwara Y, Oka S, Tanaka S, Nakamura T, Saito S, Fukunaga Y, Takamatsu M, Kawachi H, Hotta K, Ikematsu H, Kojima M, Saito Y, Yamada M, Kanemitsu Y, Sekine S, Nagata S, Yamada K, Kobayashi N, Ishihara S, Saitoh Y, Matsuda K, Togashi K, Komori K, Ishiguro M, Kuwai T, Okuyama T, Ohuchi A, Ohnuma S, Sakamoto K, Sugai T, Katsumata K, Matsushita HO, Yamano HO, Eda H, Uraoka T, Akimoto N, Kobayashi H, Ajioka Y, Sugihara K, Ueno H. Nomogram as a novel predictive tool for lymph node metastasis in T1 colorectal cancer treated with endoscopic resection: a nationwide, multicenter study. Gastrointestinal endoscopy, 97:1119-1128.e5, 2023
18. Kojima M, Yokota M, Yanagisawa N, Kitamura S, Amemiya K, Kawano S, Tsukada Y, Sakuyama N, Nagayasu K, Hashimoto T, Nakashima K, Jiang K, Kanemitsu Y, Fujita F, Akiba J, Notohara K, Itakura J, Sekine S, Sakashita S, Sakamoto N, Ishikawa S, Nakanishi Y, Yao T, Liang WY, Lauwers GY, Ito M, Sakamoto K, Ishii G, Ochiai A. Assessment of Elastic Laminal Invasion Contributes to an Objective pT3 Subclassification in Colon Cancer. The American journal of surgical pathology, 47:1122-1133, 2023
19. Yoshida T, Yatabe Y, Kato K, Ishii G, Hamada A, Mano H, Sunami K, Yamamoto N, Kohno T. The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan. Cancer biology & medicine, 21:29-44, 2023
20. Tanabe K, Nakanishi Y, Okubo N, Matsumoto S, Umino Y, Kataoka M, Yajima S, Yoshida T, Miyazaki S, Kuwata T, Ishii G, Watanabe R, Masuda H. Prevalence and characteristics of patients with upper urinary tract urothelial carcinoma having potential Lynch syndrome identified by immunohistochemical universal screening and Amsterdam criteria II. BMC cancer, 23:940, 2023
21. Miyasaka Y, Hiyama T, Kuno H, Shinozaki T, Sakashita S, Kobayashi T. Characteristic imaging findings in a patient with chronic expanding hematoma on the floor of the mouth. International cancer conference journal, 12:185-189, 2023
22. Furue Y, Hori K, Tomioka T, Fujii S, Okano W, Shinozaki T, Kadota T, Yoda Y, Hayashi R, Yano T. Clinical outcome of endoscopic-assisted transoral surgery for superficial cancer of pharyngo-esophageal junction. Head & neck, 45:2098-2107, 2023
23. Takeshita N, Enokida T, Okano S, Fujisawa T, Wada A, Sato M, Tanaka H, Tanaka N, Onaga R, Hoshi Y, Sakashita S, Ishii G, Tahara M. Weekly paclitaxel, carboplatin and cetuximab (PCE) combination followed by nivolumab for recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). Oral oncology, 147:106615, 2023
24. Konishi Y, Taki T, Nakai T, Kuroe T, Morisue R, Miyoshi T, Tane K, Samejima J, Aokage K, Miyazaki S, Sakamoto N, Sakashita S, Watanabe R, Kojima M, Suzuki K, Tsuboi M, Ishii G. Clinicopathological features and prognostic impact of dirty necrosis in metastatic lung cancers from the colon and rectum. Cancer science, 114:2169-2177, 2023
25. Ohtani-Kim SJ, Taki T, Tane K, Miyoshi T, Samejima J, Aokage K, Nagasaki Y, Kojima M, Sakashita S, Watanabe R, Sakamoto N, Goto K, Tsuboi M, Ishii G. Efficacy of Preoperative Biopsy in Predicting the Newly Proposed Histologic Grade of Resected Lung Adenocarcinoma. Modern pathology, 36:100209, 2023
26. Tanaka T, Umemura S, Miyoshi T, Nakai T, Noritake O, Suzuki J, Tane K, Samejima J, Aokage K, Mimaki S, Tsuchihara K, Taki T, Miyazaki S, Watanabe R, Sakashita S, Sakamoto N, Kojima M, Goto K, Ikeda N, Tsuboi M, Ishii G. The prognostic impact of a high number of peritumoral alveolar macrophages in neuroendocrine carcinoma in the lung. Pathology international, 73:497-508, 2023
27. Tanaka Y, Nakai T, Suzuki A, Kagawa Y, Noritake O, Taki T, Hashimoto H, Sakai T, Shibata Y, Izumi H, Nosaki K, Udagawa H, Zenke Y, Matsumoto S, Yoh K, Miyazaki S, Sakamoto N, Sakashita S, Kojima M, Watanbe R, Tsuboi M, Goto K, Ishii G. Clinicopathological significance of peritumoral alveolar macrophages in patients with resected early-stage lung squamous cell carcinoma. Cancer immunology, immunotherapy, 72:2205-2215, 2023
28. Kagawa Y, Nakai T, Taki T, Hashimoto H, Tanaka Y, Sakai T, Shibata Y, Izumi H, Nosaki K, Udagawa H, Zenke Y, Matsumoto S, Yoh K, Miyazaki S, Watanabe R, Kojima M, Sakashita S, Sakamoto N, Tsuboi M, Goto K, Ishii G. Prognostic impact and gene expression analysis of peri-tumoral alveolar macrophage in resected lung adenocarcinoma. Cancer science, 114:3423-3432, 2023
29. Adachi M, Aoyama N, Kojima M, Sakamoto N, Miyazaki S, Taki T, Watanabe R, Matsuura K, Kotani D, Kojima T, Fujita T, Tabuchi K, Ishii G, Sakashita S. The area of residual tumor predicts esophageal squamous cell carcinoma prognosis following neoadjuvant chemotherapy. Journal of cancer research and clinical oncology, 149:4663-4673, 2023
30. Akimoto E, Kuwata T, Shitara K, Kawazoe A, Sakamoto N, Ishii G, Ochiai A, Kinoshita T. Impact of Programmed Death-Ligand 1 Expression on Mismatch Repair Deficiency and Epstein-Barr Virus Status on Survival Outcomes in Patients with Stage II/III Gastric Cancer After Surgery. Annals of surgical oncology, 30:5227-5236, 2023
31. Du J, Kageyama SI, Yamashita R, Tanaka K, Okumura M, Motegi A, Hojo H, Nakamura M, Hirata H, Sunakawa H, Kotani D, Yano T, Kojima T, Hamaya Y, Kojima M, Nakamura Y, Suzuki A, Suzuki Y, Tsuchihara K, Akimoto T. Transposable elements potentiate radiotherapy-induced cellular immune reactions via RIG-I-mediated virus-sensing pathways. Communications biology, 6:818, 2023
32. Oyoshi H, Du J, Sakai SA, Yamashita R, Okumura M, Motegi A, Hojo H, Nakamura M, Hirata H, Sunakawa H, Kotani D, Yano T, Kojima T, Nakamura Y, Kojima M, Suzuki A, Zenkoh J, Tsuchihara K, Akimoto T, Shibata A, Suzuki Y, Kageyama SI. Comprehensive single-cell analysis demonstrates radiotherapy-induced infiltration of macrophages expressing immunosuppressive genes into tumor in esophageal squamous cell carcinoma. Science advances, 9:eadh9069, 2023
33. Igata Y, Kojima M, Suzuki T, Ishii G, Morisue R, Suzuki T, Kudo M, Sugimoto M, Kobayashi S, Martin JD, Stylianopoulos T, Cabral H, Kano MR, Konishi M, Gotohda N. Relationships between physical and immunological tumor microenvironment in pancreatic ductal adenocarcinoma. Cancer science, 114:3783-3792, 2023
34. Morisue R, Kojima M, Suzuki T, Watanabe R, Sakamoto N, Sakashita S, Harada K, Nakai T, Ishii G, Nakatsura T, Gotohda N, Ishikawa S. Common clinicopathological and immunological features of sarcomatoid carcinoma across organs: A histomorphology-based cross-organ study. International journal of cancer, 153:1997-2010, 2023
35. Satake T, Shibuki T, Watanabe K, Sasaki M, Imaoka H, Mitsunaga S, Kojima M, Ikeda M. Case Report: Atezolizumab plus bevacizumab for combined hepatocellular-cholangiocarcinoma. Frontiers in oncology, 13:1234113, 2023
36. Oda S, Kuno H, Hiyama T, Sakashita S, Sasaki T, Kobayashi T. Computed tomography-based radiomic analysis for predicting pathological response and prognosis after neoadjuvant chemotherapy in patients with locally advanced esophageal cancer. Abdominal radiology (New York), 48:2503-2513, 2023
37. Kondo R, Sakamoto N, Harada K, Hashimoto H, Morisue R, Yanagihara K, Kinoshita T, Kojima M, Ishii G. Cancer-associated fibroblast-dependent and -independent invasion of gastric cancer cells. Journal of cancer research and clinical oncology, 149:5309-5319, 2023
38. Sakashita S, Sakamoto N, Kojima M, Taki T, Miyazaki S, Minakata N, Sasabe M, Kinoshita T, Ishii G, Ochiai A. Requirement of image standardization for AI-based macroscopic diagnosis for surgical specimens of gastric cancer. Journal of cancer research and clinical oncology, 149:6467-6477, 2023