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

Abstract

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