Annual Report 2022
Department of Pathology and Clinical Laboratories
Genichiro Ishii, Reiko Watanabe, Tetsuro Taki, Saori Miyazaki, Motohiro Kojima, Shingo Sakashita, Naoya Sakamoto, Takeshi Kuwata, Shohei Murata, Masahiro Adachi, Takumi Kitaoka, Hirohiko Miyake, Satoshi Fujii, Hiroki Imada
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 2022 is listed in Table 1. We conducted the following pathological diagnoses this year: 14,464 biopsy specimens, 3,693 intraoperative tissue specimens, 5,435 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.
Table1. Number of pathology and cytology samples examined in the Pathology Division in 2022
The Team and What We Do
Weekly meetings are regularly held with residents, and hypotheses inspired by Clinical Questions are developed into research papers. 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. 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. In addition, in support of the TITANIA study, we are cooperating in the collection of specimens.
Research Activities
The following are this year's major research results.
1. We found that fibroblast-dependent and fibroblast-independent mechanisms exist in the invasion mechanism of cancer cells.
2. A clinicopathological study of tertiary lymphoid structure positive cases in adenocarcinoma of the lung was performed.
3. We found dirty necrosis in lung metastases of colorectal cancer correlates with poor prognosis.
4. We revealed area of residual tumor (ART) is an independent poor prognostic factor in surgically treated esophageal cancer.
5. We found that patients with lung adenocarcinoma with a high number of peritumoral alveolar macrophages have a poor prognosis.
6. We reported the clinicopathologic importance of tumor necrosis in surgically treated pancreatic ductal adenocarcinoma.
7. We conducted the clinicopathological study in cases with a higher number of extra-tumoral lymphatic invasion and reviewed the characteristics of their immune microenvironment.
8. We found that area of residual tumor (ART) is an independent poor prognostic factor in surgically treated triple-negative breast cancer. We also revealed that there may be a group of patients other than pCR patients who can skip postoperative chemotherapy.
9. We identified that the lymph node metastases were infiltrated by a large number of tumor-promoting stromal cells in the extranodal lymph node invasion area.
10. We contributed to the industry-university collaborative national genome screening project, SCRUM-Japan, using histopathological specimens.
Clinical Trials
Pathological testing strengthens the quality control and quality assurance of clinical tests performed in the NCCHE's clinical trials.
Education
The staff of the Department of Pathology and Clinical Laboratories provide guidance to NCCHE residents regarding diagnostic training and training in pathological research. They also provide guidance to NCCHE doctoral students at Juntendo University regarding preparing their doctoral dissertations. 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
In August 2022, the laboratory obtained CAP (College of American Pathologists) accreditation. By maintaining CAP accreditation, we will actively develop LDT and introduce new diagnostic methods, aiming to develop new diagnostic methods that meet the "patient first" philosophy.
We will further promote translational research using pathology specimens.
List of papers published in 2022
Journal
1. Murano T, Ikematsu H, Shinmura K, Okumura K, Kuwata T, Ushiama M, Yoshida T, Takashima K, Nakajo K, Kadota T, Yoda Y, Oono Y, Yano T. Endoscopic management of familial adenomatous polyposis targeting colorectal lesions greater than 5 mm in size: a single-center retrospective study. Familial cancer, 22:83-89, 2023
2. 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
3. Matsuda Y, Ye J, Yamakawa K, Mukai Y, Azuma K, Wu L, Masutomi K, Yamashita T, Daigo Y, Miyagi Y, Yokose T, Oshima T, Ito H, Morinaga S, Kishida T, Minamoto T, Kojima M, Kaneko S, Haba R, Kontani K, Kanaji N, Okano K, Muto-Ishizuka M, Yokohira M, Saoo K, Imaida K, Suizu F. Association of longer telomere length in cancer cells and cancer-associated fibroblasts with worse prognosis. Journal of the National Cancer Institute, 115:208-218, 2023
4. Morii E, Hatanaka Y, Motoi N, Kawahara A, Hamakawa S, Kuwata T, Nagatomo T, Oda Y, Okamoto A, Tanaka R, Iyoda A, Ichiro M, Matsuo Y, Nakamura N, Nakai T, Fukuhara M, Tokita K, Yamaguchi T, Takenaka M, Kawabata A, Hatanaka KC, Tsubame K, Satoh Y. Guidelines for Handling of Cytological Specimens in Cancer Genomic Medicine. Pathobiology, 1-23, 2023
5. Morishita Y, Sakashita S, Tomioka T, Okano W, Shinozaki T, Higashino T, Matsuura K, Hayashi R. Human papillomavirus-related multiphenotypic sinonasal carcinoma. Auris, nasus, larynx, 50:151-155, 2023
6. Kuroe T, Watanabe R, Morisue R, Miyazaki S, Kojima M, Murata SC, Nakai T, Taki T, Sakashita S, Sakamoto N, Matsubara N, Masuda H, Ushiku T, Ishii G. Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation. Cancer medicine, 12:4557-4567, 2023
7. Sakai T, Aokage K, Miyoshi T, Tane K, Ishii G, Goto K, Tsuboi M. Tumor size exceeding 5 cm as a valid prognostic factor in all stages of thymic epithelial tumors. Surgery today, 53:42-50, 2023
8. 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
9. 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
10. 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, 2023
11. 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, 2023
12. Kotani D, Nakamura Y, Fujisawa T, Bando H, Sakamoto N, Johns AL, Park K, Casolino R, Yoshino T, Biankin AV. ICGC-ARGO precision medicine: an update on targeted therapy based on longitudinal analysis of tumour heterogeneity and evolution in colorectal cancer. The Lancet. Oncology, 24:20-21, 2023
13. Nakagama Y, Chi SG, Minami Y, Watanabe R, Yamagishi M, Atsuko U, Kido Y. Patients with B-cell malignancies experience reduced antibody responses with class switching defect following BNT162b2 SARS-CoV-2 vaccination. Journal of infection and chemotherapy, 29:112-114, 2023
14. Masuoka S, Hiyama T, Kuno H, Sekiya K, Sakashita S, Kobayashi T. Imaging Approach for Cervical Lymph Node Metastases from Unknown Primary Tumor. Radiographics, 43:e220071, 2023
15. Hattori H, Sakashita S, Tsuboi M, Ishii G, Tanaka T. Tumor-identification method for predicting recurrence of early-stage lung adenocarcinoma using digital pathology images by machine learning. Journal of pathology informatics, 14:100175, 2023
16. Itahashi K, Irie T, Yuda J, Kumagai S, Tanegashima T, Lin YT, Watanabe S, Goto Y, Suzuki J, Aokage K, Tsuboi M, Minami Y, Ishii G, Ohe Y, Ise W, Kurosaki T, Suzuki Y, Koyama S, Nishikawa H. BATF epigenetically and transcriptionally controls the activation program of regulatory T cells in human tumors. Science immunology, 7:eabk0957, 2022
17. Nomura H, Tsuji D, Ueno S, Kojima T, Fujii S, Yano T, Daiko H, Demachi K, Itoh K, Kawasaki T. Relevance of pharmacogenetic polymorphisms with response to docetaxel, cisplatin, and 5-fluorouracil chemotherapy in esophageal cancer. Investigational new drugs, 40:420-429, 2022
18. 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, 2022
19. Morishita Y, Takenouchi K, Sakashita S, Matsuura K, Hayashi R, Nakatsura T. Immunohistochemical Analysis of Common Cancer Antigens in Head and Neck Squamous Cell Carcinoma. Anticancer research, 42:5751-5761, 2022
20. Eguchi Y, Nakai T, Kojima M, Wakabayashi M, Sakamoto N, Sakashita S, Miyazaki S, Taki T, Watanabe R, Watanuki R, Yamauchi C, Iwatani T, Mukohara T, Onishi T, Ishii G. Pathologic method for extracting good prognosis group in triple-negative breast cancer after neoadjuvant chemotherapy. Cancer science, 113:1507-1518, 2022
21. Nomura K, Nakai T, Nishina Y, Sakamoto N, Miyoshi T, Tane K, Samejima J, Aokage K, Kojima M, Sakashita S, Taki T, Miyazaki S, Watanabe R, Suzuki K, Tsuboi M, Ishii G. 18F-fluorodeoxyglucose uptake in PET is associated with the tumor microenvironment in metastatic lymph nodes and prognosis in N2 lung adenocarcinoma. Cancer science, 113:1488-1496, 2022
22. Niimi T, Nakai T, Aokage K, Tane K, Miyoshi T, Samejima J, Miyazaki S, Taki T, Sakamoto N, Sakashita S, Watanabe R, Kojima M, Suzuki K, Tsuboi M, Ishii G. Prognostic impact of count of extratumoral lymphatic permeation in lung adenocarcinoma and its relation to the immune microenvironment. Cancer science, 113:1497-1506, 2022
23. Noritake O, Aokage K, Suzuki A, Tane K, Miyoshi T, Samejima J, Yoshikawa T, Murata SC, Nakai T, Tsuboi M, Ishii G. Prognostic impact of the number of peri-tumoral alveolar macrophages in patients with stage I lung adenocarcinoma. Journal of cancer research and clinical oncology, 148:3437-3447, 2022
24. Kamigaichi A, Aokage K, Katsumata S, Ishii G, Wakabayashi M, Miyoshi T, Tane K, Samejima J, Tsuboi M. Prognostic impact of examined mediastinal lymph node count in clinical N0 non-small cell lung cancer. European journal of cardio-thoracic surgery, 62:ezac359, 2022
25. Tamiya Y, Nakai T, Suzuki A, Mimaki S, Tsuchihara K, Sato K, Yoh K, Matsumoto S, Zenke Y, Nosaki K, Izumi H, Shibata Y, Sakai T, Taki T, Miyazaki S, Watanabe R, Sakamoto N, Sakashita S, Kojima M, Hashimoto N, Tsuboi M, Goto K, Ishii G. The impact of tertiary lymphoid structures on clinicopathological, genetic and gene expression characteristics in lung adenocarcinoma. Lung cancer (Amsterdam, Netherlands), 174:125-132, 2022
26. Okunaka M, Kotani D, Demachi K, Fujiwara H, Sakashita S, Yoshino T, Fujita T, Kojima T. Significance of chemotherapy-free interval and tumor regression grade in patients with recurrent esophageal squamous cell carcinoma receiving chemotherapy with fluorouracil and platinum after esophagectomy following preoperative chemotherapy. Esophagus, 19:240-249, 2022
27. Sato D, Kadota T, Inaba A, Nishihara K, Takashima K, Nakajo K, Sawada K, Kotani D, Fujiwara H, Yoda Y, Kojima T, Fujita T, Fujii S, Yano T. Long-term clinical outcome after endoscopic resection of esophageal squamous cell carcinoma invading the muscularis mucosae without lymphovascular invasion. Gastrointestinal endoscopy, 95:634-641.e3, 2022
28. Chida K, Kawazoe A, Suzuki T, Kawazu M, Ueno T, Takenouchi K, Nakamura Y, Kuboki Y, Kotani D, Kojima T, Bando H, Mishima S, Kuwata T, Sakamoto N, Watanabe J, Mano H, Ikeda M, Shitara K, Endo I, Nakatsura T, Yoshino T. Transcriptomic Profiling of MSI-H/dMMR Gastrointestinal Tumors to Identify Determinants of Responsiveness to Anti-PD-1 Therapy. Clinical cancer research, 28:2110-2117, 2022
29. Fujii S, Kotani D, Hattori M, Nishihara M, Shikanai T, Hashimoto J, Hama Y, Nishino T, Suzuki M, Yoshidumi A, Ueno M, Komatsu Y, Masuishi T, Hara H, Esaki T, Nakamura Y, Bando H, Yamada T, Yoshino T. Rapid Screening Using Pathomorphologic Interpretation to Detect BRAFV600E Mutation and Microsatellite Instability in Colorectal Cancer. Clinical cancer research, 28:2623-2632, 2022
30. Yukami H, Kawazoe A, Lin YT, Koyama S, Fukuoka S, Hara H, Takahashi N, Kojima T, Asayama M, Yoshii T, Bando H, Kotani D, Nakamura Y, Kuboki Y, Mishima S, Wakabayashi M, Kuwata T, Goto M, Higuchi K, Yoshino T, Doi T, Nishikawa H, Shitara K. Updated Efficacy Outcomes of Anti-PD-1 Antibodies plus Multikinase Inhibitors for Patients with Advanced Gastric Cancer with or without Liver Metastases in Clinical Trials. Clinical cancer research, 28:3480-3488, 2022
31. Aoki Y, Kawazoe A, Kubota Y, Chida K, Mishima S, Kotani D, Nakamura Y, Kuboki Y, Bando H, Kojima T, Doi T, Yoshino T, Kuwata T, Shitara K. Characteristics and clinical outcomes of patients with advanced gastric or gastroesophageal cancer treated in and out of randomized clinical trials of first-line immune checkpoint inhibitors. International journal of clinical oncology, 27:1413-1420, 2022
32. Takahashi S, Ohno I, Ikeda M, Konishi M, Kobayashi T, Akimoto T, Kojima M, Morinaga S, Toyama H, Shimizu Y, Miyamoto A, Tomikawa M, Takakura N, Takayama W, Hirano S, Otsubo T, Nagino M, Kimura W, Sugimachi K, Uesaka K. Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-label Multicenter Prospective Trial (JASPAC05). Annals of surgery, 276:e510-e517, 2022
33. Yagi N, Suzuki T, Mizuno S, Kojima M, Kudo M, Sugimoto M, Kobayashi S, Gotohda N, Ishii G, Nakatsura T. Component with abundant immune-related cells in combined hepatocellular cholangiocarcinoma identified by cluster analysis. Cancer science, 113:1564-1574, 2022
34. Kudo M, Ishii G, Gotohda N, Konishi M, Takahashi S, Kobayashi S, Sugimoto M, Martin JD, Cabral H, Kojima M. Histological tumor necrosis in pancreatic cancer after neoadjuvant therapy. Oncology reports, 48:121, 2022
35. Matsuda Y, Yamashita T, Ye J, Yasukawa M, Yamakawa K, Mukai Y, Machitani M, Daigo Y, Miyagi Y, Yokose T, Oshima T, Ito H, Morinaga S, Kishida T, Minamoto T, Yamada S, Takei J, Kaneko MK, Kojima M, Kaneko S, Masaki T, Hirata M, Haba R, Kontani K, Kanaji N, Miyatake N, Okano K, Kato Y, Masutomi K. Phosphorylation of hTERT at threonine 249 is a novel tumor biomarker of aggressive cancer with poor prognosis in multiple organs. The Journal of pathology, 257:172-185, 2022
36. Yanagihara K, Iino Y, Yokozaki H, Kubo T, Oda T, Kubo T, Komatsu M, Sasaki H, Ichikawa H, Kuwata T, Seyama T, Ochiai A. A Comparative Study of Patient-Derived Tumor Models of Pancreatic Ductal Adenocarcinoma Involving Orthotopic Implantation. Pathobiology, 89:222-232, 2022
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, 2022
38. Panagi M, Mpekris F, Chen P, Voutouri C, Nakagawa Y, Martin JD, Hiroi T, Hashimoto H, Demetriou P, Pierides C, Samuel R, Stylianou A, Michael C, Fukushima S, Georgiou P, Papageorgis P, Papaphilippou PC, Koumas L, Costeas P, Ishii G, Kojima M, Kataoka K, Cabral H, Stylianopoulos T. Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models. Nature communications, 13:7165, 2022
39. Harada K, Sakamoto N. Cancer organoid applications to investigate chemotherapy resistance. Frontiers in molecular biosciences, 9:1067207, 2022