Angiogenesis in ductal breast carcinoma. Comparison of microvessel density between primary tumour and lymph node metastasis Petroula Arapandoni-Dadioti a , Alexandra Giatromanolaki b , Helen Trihia a, b , Adrian L. Harris b, c , Michael I. Koukourakis b, * a Department of Pathology, Metaxa Cancer Hospital of Pireus, 51 Botassi St., Pireus 18537, Greece b Tumour and Angiogenesis Research Group, 18 Dimokratias Avenue, Iraklion 71306, Crete, Greece c ICRF Medical Oncology Unit, Churchill Hospital, Oxford, OX3 7LJ, UK Received 1 September 1998; accepted 9 November 1998 Abstract Angiogenesis has been recognised as an important prognostic factor in cancer. This study assessed immunohistochemically (JC70 MoAb) the microvessel score (MS; in £ 250 fields) in 35 breast ductal carcinomas with lymph node involvement. Sections from both primary tumours and invaded nodes were assessed. A significantly lower MS was observed in the metastatic foci (24:6 ^ 9 vs. 13:6 ^ 6; P , 0:0001) than in the primary lesions. However, linear regression analysis showed a significant direct correlation between the MS assessed in primary lesions and the related metastatic foci in the lymph nodes (P  0:006, r  045). The primary tumour to node (T/N) ratio was assessed; 11/35 cases had a node MS close to the score of the primary (T=N , 2), whilst 17/35 had a T/N ratio ranging from 3 to 7. Extracapsular node involvement was more frequent in cases with low T/N ratio. Angiogenesis in the metastatic foci was independent of the amount of growing stroma within the metastasis. Vessel density in the normal lymph nodes did not correlate with the MS within the node metastases. We conclude that cancer cells migrating to the nodes may have similar angiogenic abilities to the parental cells of the primary tumour. However, environmental factors probably related to node immune reaction against the invading tumour could be responsible for the reduced angiogenicity in the nodes. Further studies are required to investigate the suggested angiogenesis suppressing immune mechanisms occurring in the invaded lymph nodes of breast cancer patients and possible clinical implications. q 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Angiogenesis; Breast cancer; Lymph node 1. Introduction The role of angiogenesis in the pathogenesis of cancer invasion and metastasis has been under intense investigation during last decade. Tumours with high vasculature have a higher incidence of distant or node metastasis and a poorer prognosis [1–4]. It has been suggested that angiogenic cancer clones are required for vessel formation, invasion into vessels and for the subsequent installation and growth in distant organs [5,6]. Up to now there has been little information relating to humans on whether metastasising cells to organs or Cancer Letters 137 (1999) 145–150 0304-3835/99/$ - see front matter q 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S0304-3835(98)00343-7 * Corresponding author. Tel.: 1 30-81-392498; fax: 1 30-81- 392848. E-mail address: targ@her.forthnet.gr (M.I. Koukourakis)