title: Significance of lymph vessel invasion identified by the endothelial lymphatic marker D2-40 in node negative breast cancer.
abstract: Monoclonal antibody D2-40, a marker of lymphatic endothelium, identifies tumor emboli in lymph vessels. The aim of the study was to assess whether D2-40+ lymph vessel invasion (LVI) correlates with clinicopathologic factors including lymphovascular invasion (LVI) as assessed by haematoxylin and eosin-stained sections (H&E+ or H&E-) and to assess the prognostic significance in node-negative breast cancer. The study group consisted of 303 node-negative breast cancer patients that had a median follow-up of 7.6 years. Clinical and pathological data were retrieved from the Henrietta Banting database. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections of the primary invasive carcinoma using D2-40. Immunostaining with CD31 was performed on the discordant cases that were H&E+/D2-40-. D2-40+ lymph vessel invasion was detected in 82/303 (27%) cases. The foci of lymphatic invasion occurred predominantly at the invasive front of the tumor. The absence of D2-40 and CD31 in 13/17 discordant cases was suggestive of retraction artefact. D2-40+ lymph vessel invasion correlated significantly with age (P=0.0003), tumor size (P=0.005), histological grade (P=0.0001), H&E+ (P=<0.0001) and estrogen receptor status (P=0.005) but not with histological type or progesterone receptor status. Multivariate analysis revealed that D2-40+ lymph vessel invasion was the only significant predictor of distant recurrence. There was no significant association between D2-40 status and local recurrence (P=0.752) or regional recurrence (P=0.13). Both D2-40+lymph vessel invasion (P=0.009) and H&E+LVI cases (P=0.02) were associated with overall shorter survival in univariate analysis. These data indicate that D2-40 identifies lymphatic invasion in breast tumors and is a significant predictor of outcome in breast cancer.
authors.affiliation: Department of Surgery, Sunnybrook Health Sciences Centre and Women's College Hospital, University of Toronto, Toronto, ON, Canada.
authors.forename: Angel
authors.initials: A
authors.lastname: Arnaout-Alkarain
authors.forename: Harriette J
authors.initials: HJ
authors.lastname: Kahn
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: Ping A
authors.initials: PA
authors.lastname: Sun
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Marks
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000378:metabolism*; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008198:Lymph Nodes / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000175:diagnosis; D009360:Neoplastic Cells, Circulating / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000032:analysis / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; C500987:monoclonal antibody D2-40