Prognostic Value of Lymphangiogenesis Determinants in Luminal and Non-luminal Breast Carcinomas

Document Type : Research Articles


1 Department of Anatomical Pathology, Faculty of Medicine, University Gadjah Mada, Indonesia.

2 Department of Surgery, Faculty of Medicine, University Gadjah Mada, Indonesia.


Background: Breast carcinomas (BCs) are sub-classified according to the molecular characteristics into luminal and
non-luminal subtypes that clinically show different biological behavior, treatment and prognosis. BCs spread primarily
through lymphatic vessels using cascade processes of lymphagiogenesis in which VEGF-C plays an important role during
lymph node metastasis. Prognostic value of VEGF-C in luminal and non-luminal BC is still unclear and has not been
studied thoroughly to clarify and define prognosis and therapeutic monitoring. Aim: To define the prognostic value of
lymphangiogenesis on survival rates of luminal and non-luminal subtypes BC. Materials and Methods: This study
applied prospective cohort design, using 130 patients of invasive duct carcinoma of the breast, stage I-IIIA, from
Sardjito General Hospital, Indonesia and subsequent longitudinal follow-up. Immunohistochemical staining was
carried out using anti-ER, -PR, -Her-2, VEGF-C, VEGFR-3 and D2-40 antibodies. The related clinicopathologic
characteristics of BC patients and lymphangiogenesis determinants, including VEGF-C expression, were statistically
analyzed. Results: In non-luminal BC subtypes, VEGF-C expression (HR=0.04; 95% CI=0.01-0.41), lymph node
metastasis (HR=0.14; 95% CI=0.04-0.55) and stage (HR=0.30; 95% CI= 0.02-0.76) were determined as independent
prognostic factors on survival rates. However, the lymphangiogenesis determinants were not associated with the survival
rates of luminal BC subtypes. Conclusion: This study suggested that lymphangiogenesis affects survival rates of
non-Luminal subtype rather than the luminal subtypes of BC.


Main Subjects