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Antibody\u2013drug conjugates (ADCs) are a promising therapeutic modality that selectively delivers cytotoxic payloads to tumors via cell-surface antigens. Tumor-associated calcium signal transducer 2 (TROP2,\n                      <jats:italic>TACSTD2<\/jats:italic>\n                      ) has shown therapeutic potential as an ADC target in several malignancies; however, its clinical significance in ESCC remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An institutional cohort of ESCC patients treated at Kindai University was retrospectively evaluated by immunohistochemistry (n=70) and RNA sequencing (n=27).\n                      <jats:italic>TACSTD2<\/jats:italic>\n                      copy number alterations, RNA expression, and survival were analyzed using the Cancer Genome Atlas (TCGA) ESCC dataset. IHC was assessed in both resected and biopsy specimens, including metastatic lesions. Survival analyses were performed, stratifying patients by cohort-specific median\n                      <jats:italic>TACSTD2<\/jats:italic>\n                      expression levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Immunohistochemistry analysis demonstrated uniformly strong TROP2 expression in all evaluable primary and metastatic lesions. In the TCGA dataset,\n                      <jats:italic>TACSTD2<\/jats:italic>\n                      mRNA expression was consistently high, irrespective of copy-number status, and was comparable to or higher than that observed in non-small cell lung cancer and breast cancer, tumor types in which TROP2-targeted ADCs are clinically active. The\n                      <jats:italic>TACSTD2<\/jats:italic>\n                      high-expression group showed a trend toward worse overall survival in both the institutional and the TCGA cohort, whereas disease-free survival was similar.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      TROP2\/\n                      <jats:italic>TACSTD2<\/jats:italic>\n                      is strongly and consistently expressed in ESCC at the protein and RNA levels, despite infrequent gene amplification, supporting its feasibility as a therapeutic target. High expression shows a trend toward poorer overall survival, warranting validation in larger cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10388-026-01257-5","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T23:45:46Z","timestamp":1789861546000},"page":"1003-1013","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor-associated calcium signal transducer 2 expression as a promising therapeutic target in esophageal squamous cell carcinoma: a combined the Cancer Genome Atlas and an institutional cohort"],"prefix":"10.1007","volume":"23","author":[{"given":"Chiaki","family":"Inagaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3280-4850","authenticated-orcid":false,"given":"Hisato","family":"Kawakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiichiro","family":"Mitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Iijima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Matoba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiko","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Shiraisi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takushi","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"issue":"3","key":"1257_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2022","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. 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R03-224) in accordance with the Declaration of Helsinki. Informed consent was not required for this retrospective study.","order":1,"name":"Ethics","label":"Ethical Statement","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"C. Inagaki has received grants\/contracts from Ono Pharmaceutical Co., Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Co., and JSMO\/KFCR (grants for young researchers); has received lecture\/presentation honoraria from Daiichi Sankyo\/UCB Japan, MSD K.K., Taiho Pharmaceutical, Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Bristol Myers Squibb Company, CareNet. Inc., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., and the Japanese Society of Medical Oncology; has received travel\/meeting support from Johnson & Johnson and the Japan Clinical Cancer Research Organization. H. Kawakami has received grants\/contracts from Eisai, Bristol Myers Squibb Company, Kobayashi Pharmaceutical, Astellas Pharma Inc., Hitachi, and Ono Pharmaceutical Co., Ltd.; has received royalties\/licenses from MEDICAL & BIOLOGICAL LABORATORIES; has received consulting fees from Daiichi Sankyo, Astellas Pharma Inc., and AbbVie; has received lecture\/presentation honoraria from Bristol Myers Squibb Company, Bayer, Eli Lilly, MSD, Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Merck Biopharma, Takeda Pharmaceutical Co., Takata, Taiho, Otsuka, Nippon Kayaku, GlaxoSmithKline, Amgen, Novartis, BeOne, AstraZeneca, and Miyarisan. S. Mitani has received grants\/contracts from Caris Life Science; has received payment or honoraria for lectures\/presentations\/educational events from Taiho Pharmaceutical Co., MSD K.K., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., and Daiichi Sankyo Co., Ltd.; has participated on an Advisory Board\/DSMB for Chugai Pharmaceutical Co., Ltd. H. Iijima, R. Matoba, A.Ito, O. Shiraisi, and T. Yasuda has reported no conflicts of interest. H. Hayashi has received grants or contracts from IQVIA Services JAPAN K.K., Eisai Co., Ltd., SYNEOS HEALTH CLINICAL K.K., Shionogi & Co., Ltd., EP-CRSU CO., LTD., Nippon Kayaku Co., Ltd., EPS Corporation, GlaxoSmithKline K.K., Otsuka Pharmaceutical Co., Ltd., Sanofi K.K., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Bristol Myers Squibb Company, Amgen Inc., SRL Medisearch Inc., Chugai Pharmaceutical Co., Ltd., PRA Health Sciences Inc., Nippon Boehringer Ingelheim Co., Ltd., CMIC CO., Ltd., Janssen Pharmaceutical K.K., Pfizer R&D Japan G.K., Astellas Pharma Inc., Ascent Development Services, Labcorp Development Japan K.K., Eisai Inc., Kobayashi Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Pfizer Japan Inc., AstraZeneca K.K., AbbVie Inc., Daiichi Sankyo Co., Ltd., A2 Healthcare Corp., Novartis Pharma K.K., Eli Lilly Japan K.K., Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Medpace Japan KK, Sysmex Corporation, ICON Japan K.K., Clinical Research Support Center Kyushu, PPD-SNBL K.K., Kyushu Study group of Clinical Cancer, Mochida Pharmaceutical Co., Ltd., Public Health Research Foundation, Japanese Gastric Cancer Association, Thoracic Oncology Research Group, West Japan Oncology Group, Japan Clinical Cancer Research Organization, and Comprehensive Support Project for Oncological Research of Breast Cancer; has received payment or honoraria for lectures\/presentations\/educational events from Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., AstraZeneca K.K., Bristol Myers Squibb Company, MSD K.K., Takeda Pharmaceutical Co., Ltd., Sysmex Corporation, Novartis Pharma K.K., Nippon Boehringer Ingelheim Co., Ltd., Pfizer Japan Inc., AbbVie Inc., Chugai Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Amgen Inc., Reno. Medical K.K., Eisai Co., Ltd., Nippon Kayaku Co., Ltd., Janssen Pharmaceutical K.K., Hisamitsu Pharmaceutical Co., Inc., Care Net, Inc., Novocure K.K., Taiho Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Daiichi Sankyo Co., Ltd., 3H Clinical Trial Inc., Guardant Health Japan Corp, Ishiyaku Publishers, Inc., and Medical Review Co., Ltd; has served on a Data Safety Monitoring Board or Advisory Board for Bristol Myers Squibb Company, AstraZeneca K.K., Janssen Pharmaceutical K.K., Daiichi Sankyo Co., Ltd., AbbVie Inc., Novocure K.K., and Chugai Pharmaceutical Co., Ltd.","order":2,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":3,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}}]}}