{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:31:39Z","timestamp":1790875899048,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004043","name":"Kanazawa Medical University","doi-asserted-by":"publisher","award":["K2025-21"],"award-info":[{"award-number":["K2025-21"]}],"id":[{"id":"10.13039\/501100004043","id-type":"DOI","asserted-by":"publisher"}]},{"award":["K2025-21"],"award-info":[{"award-number":["K2025-21"]}],"id":[{"id":"https:\/\/ror.org\/0535cbe18","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background\/Objectives: Conventional assessments of lymphatic invasion in the primary tumor may fail to identify lymph node metastasis (LNM) in breast cancer. We evaluated periarterial or perivenous invasion (periA\/V), using Elastica\u2013van Gieson (EVG)-stained sections, as a histological marker associated with LNM in invasive breast carcinoma of no special type (IBC-NST), focusing on the impact of invasive tumor size. Methods: We retrospectively analyzed 213 IBC-NST cases. PeriA\/V was defined as tumor nests in direct contact with perivascular elastic fibers on EVG-stained sections. Diagnostic performance was compared with that of conventional LI markers (hematoxylin and eosin and D2-40), with stratified analyses by pathological T category (pT1 vs. pT2\u20134) and pT1 subcategories (pT1a, pT1b, and pT1c). Results: LNM was observed in 87 cases (40.8%). Overall, periA\/V demonstrated high sensitivity (97.7%) and negative predictive value (NPV; 93.5%). In pT1 tumors (n = 130), periA\/V achieved 100% sensitivity and 100% NPV (27\/27), and was consistently present in all node-positive pT1b\u2013c tumors. In multivariate analyses, periA\/V remained independently associated with LNM in the pT1 group (odds ratio [OR]: 16.08, p = 0.003) and pT1c subgroup (OR: 14.7, p = 0.010). In pT2\u20134 tumors, periA\/V became frequent regardless of nodal status, indicating reduced discriminatory value. Conclusions: In this exploratory single-center cohort, EVG-based periA\/V demonstrated high sensitivity for LNM in pT1 IBC-NSTs, with periA\/V negativity consistently observed among node-negative cases. These preliminary findings suggest that periA\/V may potentially contribute to LNM risk assessment in early-stage breast cancer.<\/jats:p>","DOI":"10.3390\/diseases14050177","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:35:43Z","timestamp":1779176143000},"page":"177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["EVG-Based Periarterial\/Perivenous Invasion (periA\/V) as a High-Sensitivity Surrogate Marker for Lymph Node Metastasis in pT1 Invasive Breast Carcinoma of No Special Type"],"prefix":"10.3390","volume":"14","author":[{"given":"Chikara","family":"Mashiba","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1863-5368","authenticated-orcid":false,"given":"Akihiro","family":"Shioya","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0514-8584","authenticated-orcid":false,"given":"Takanobu","family":"Takata","sequence":"additional","affiliation":[{"name":"Division of Molecular and Genetic Biology, Department of Life Science, Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan"},{"name":"Department of Pharmacy, Kanazawa Medical University Hospital, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8979-3981","authenticated-orcid":false,"given":"Motona","family":"Kumagai","sequence":"additional","affiliation":[{"name":"Department of Pathophysiological and Experimental Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyako","family":"Shimasaki","sequence":"additional","affiliation":[{"name":"Department of Pathophysiological and Experimental Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeru","family":"Oyama","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Haba","sequence":"additional","affiliation":[{"name":"Department of Breast Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emi","family":"Morioka","sequence":"additional","affiliation":[{"name":"Department of Breast Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8886-9517","authenticated-orcid":false,"given":"Masafumi","family":"Inokuchi","sequence":"additional","affiliation":[{"name":"Department of Breast Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2662-0024","authenticated-orcid":false,"given":"Sohsuke","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku 920-0293, Ishikawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155407","DOI":"10.1016\/j.prp.2024.155407","article-title":"Periarterial or perivenous invasion is an independent indicator of lymph node metastasis in invasive breast carcinoma of no special type","volume":"260","author":"Shioya","year":"2024","journal-title":"Pathol. Res. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100316","DOI":"10.1016\/j.esmoop.2021.100316","article-title":"Lymphovascular invasion has a significant prognostic impact in patients with early breast cancer, results from a large, national, multicenter, retrospective cohort study","volume":"6","author":"Houvenaeghel","year":"2021","journal-title":"ESMO Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1093\/jnci\/djp090","article-title":"Population-based study of peritumoral lymphovascular invasion and outcome among patients with operable breast cancer","volume":"101","author":"Ejlertsen","year":"2009","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"198","DOI":"10.4048\/jbc.2011.14.3.198","article-title":"The role of lymphovascular invasion as a prognostic factor in patients with lymph node-positive operable invasive breast cancer","volume":"14","author":"Song","year":"2011","journal-title":"J. Breast Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1002\/cncr.26711","article-title":"The prognostic significance of lymphovascular invasion in invasive breast carcinoma","volume":"118","author":"Rakha","year":"2012","journal-title":"Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e8490","DOI":"10.1097\/MD.0000000000008490","article-title":"Prognostic significance of lymphatic vessel invasion diagnosed by D2-40 in Chinese invasive breast cancers","volume":"96","author":"He","year":"2017","journal-title":"Medicine"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lee, S.J., Go, J., Ahn, B.S., Ahn, J.H., Kim, J.Y., Park, H.S., Kim, S.I., Park, B.W., and Park, S. (2023). Lymphovascular invasion is an independent prognostic factor in breast cancer irrespective of axillary node metastasis and molecular subtypes. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1269971"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0002-9610(02)00950-9","article-title":"Lymph node status combined with lymphovascular invasion creates a more powerful tool for predicting outcome in patients with invasive breast cancer","volume":"184","author":"Woo","year":"2002","journal-title":"Am. J. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Takada, K., Kashiwagi, S., Asano, Y., Goto, W., Kouhashi, R., Yabumoto, A., Morisaki, T., Shibutani, M., Takashima, T., and Fujita, H. (2020). Prediction of lymph node metastasis by tumor-infiltrating lymphocytes in T1 breast cancer. BMC Cancer, 20.","DOI":"10.1186\/s12885-020-07101-y"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1097\/00000658-199911000-00012","article-title":"Lymphatic invasion, tumor size, and age are independent predictors of axillary lymph node metastases in women with T1 breast cancers","volume":"230","author":"Gajdos","year":"1999","journal-title":"Ann. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1172\/JCI71606","article-title":"Mechanisms of lymphatic metastasis","volume":"124","author":"Karaman","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1152\/physrev.00039.2021","article-title":"Lymphatic vessels in cancer","volume":"102","author":"Dieterich","year":"2022","journal-title":"Physiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/cncr.11464","article-title":"Insights into the mechanisms of lymph node metastasis","volume":"98","author":"Nathanson","year":"2003","journal-title":"Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1097\/PAS.0b013e31806841f6","article-title":"Improved methods of detection of lymphovascular invasion demonstrate that it is the predominant method of vascular invasion in breast cancer and has important clinical consequences","volume":"31","author":"Mohammed","year":"2007","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1097\/01.LAB.0000028824.03032.AB","article-title":"A new monoclonal antibody, D2-40, for detection of lymphatic invasion in primary tumors","volume":"82","author":"Kahn","year":"2002","journal-title":"Lab. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1097\/PAI.0b013e3181c65141","article-title":"Podoplanin expression in basal and myoepithelial cells: Utility and potential pitfalls","volume":"18","author":"Kanner","year":"2010","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/PAI.0b013e31828a83c5","article-title":"Value of podoplanin as an immunohistochemical marker in tumor diagnosis: A review and update","volume":"22","year":"2014","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_18","first-page":"175","article-title":"D2-40: An additional marker for myoepithelial cells of breast and the precaution in interpreting tumor lymphovascular invasion","volume":"4","author":"Ren","year":"2011","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1309\/M7D5KTVYYE51XYQA","article-title":"Diagnostic implications of podoplanin expression in peripheral nerve sheath neoplasms","volume":"129","author":"Jokinen","year":"2008","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"208","DOI":"10.21873\/cdp.10203","article-title":"Perineural invasion predicts unfavorable prognosis in patients with invasive breast cancer","volume":"3","author":"Hosoya","year":"2023","journal-title":"Cancer Diagn. Progn."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12781","DOI":"10.1038\/s41598-021-92343-4","article-title":"Perineural invasion as a risk factor for locoregional recurrence of invasive breast cancer","volume":"11","author":"Narayan","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1097\/01.pas.0000213316.59176.9b","article-title":"Extensive retraction artifact correlates with lymphatic invasion and nodal metastasis and predicts poor outcome in early stage breast carcinoma","volume":"31","author":"Acs","year":"2007","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"478","DOI":"10.4048\/jbc.2012.15.4.478","article-title":"Differentiating lymphovascular invasion from retraction artifact on histological specimen of breast carcinoma and their implications on prognosis","volume":"15","author":"Zaorsky","year":"2012","journal-title":"J. Breast Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/bmt.2012.244","article-title":"Investigation of the freely available easy-to-use software \u201cEZR\u201d for medical statistics","volume":"48","author":"Kanda","year":"2013","journal-title":"Bone Marrow Transplant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2325\/jbcs.978","article-title":"Immunohistochemical assessment of hormone receptor status using a new scoring system (J-score) in breast cancer","volume":"14","author":"Kurosumi","year":"2007","journal-title":"Breast Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.5858\/arpa.2018-0902-SA","article-title":"Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology\/College of American Pathologists clinical practice guideline focused update","volume":"142","author":"Wolff","year":"2018","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1002\/j.2040-4603.2019.tb00063.x","article-title":"Lymphatic vessel network structure and physiology","volume":"9","author":"Breslin","year":"2018","journal-title":"Compr. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1053\/j.tvir.2013.12.002","article-title":"Breast anatomy for the interventionalist","volume":"17","author":"Jesinger","year":"2014","journal-title":"Tech. Vasc. Interv. Radiol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kuhn, E., Gambini, D., Despini, L., Asnaghi, D., Runza, L., and Ferrero, S. (2023). Updates on lymphovascular invasion in breast cancer. Biomedicines, 11.","DOI":"10.3390\/biomedicines11030968"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/cup.12036","article-title":"The utility of elastic Verhoeff-Van Gieson staining in dermatopathology","volume":"40","author":"Kazlouskaya","year":"2012","journal-title":"J. Cutan. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Huang, J.C., and Bhaskar, S.M.M. (2022). Clot morphology in acute ischemic stroke decision making. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012373"}],"container-title":["Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/5\/177\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T08:09:57Z","timestamp":1779178197000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-9721\/14\/5\/177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,19]]},"references-count":31,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["diseases14050177"],"URL":"https:\/\/doi.org\/10.3390\/diseases14050177","relation":{},"ISSN":["2079-9721"],"issn-type":[{"value":"2079-9721","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,19]]}}}