Lymphangiogenesis and lymph node metastasis in breast cancer

Giles H Cunnick¹ , Wen G Jiang¹ , Tony Douglas-Jones² , Gareth Watkins¹ , Kelvin F Gomez¹ , Mike J Morgan² , Ashok Subramanian³ , Kefah Mokbel³ and Robert E Mansel¹

¹Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff, CF14 4XN, Wales, UK

²Dept of Histopathology, Cardiff University School of Medicine, Cardiff, CF14 4XN, Wales, UK

³Department of breast surgery, St. George's Hospital, Tooting, London, SW17 0QT, England, UK

author email corresponding author email

Molecular Cancer 2008, 7:23doi:10.1186/1476-4598-7-23


Published:	6 March 2008

Abstract

Introduction

There have been few studies on lymphangiogenesis in the past due to the lack of specific lymphatic endothelial markers, and lymphatic-specific growth factors. Recently, these limitations have been relieved by the discovery of a small number of potential lymphatic-specific markers. The relationship between lymphangiogenesis and regional or distant metastasis has not previously been investigated in humans. Using these lymphatic markers, it is possible to explore the relationship between lymphangiogenesis and tumour metastasis. This study indirectly quantified lymphangiogenesis by measuring mRNA expression of all seven lymphatic markers described above in breast cancers and correlated these markers with lymphatic involvement and survival.

The cDNA from 153 frozen archived breast samples were analysed with Q-PCR for all seven lymphangiogenic markers. This was correlated with various prognostic factors as well as patient survival.

Results

There was significantly greater expression of all 7 markers in malignant compared to benign breast tissue. In addition, there was greater expression in lymph node positive/grade 3 tumours when compared to lymph node negative/grade 1 tumours. In 5 of the markers, there was a greater expression in poor NPI prognostic tumours when compared to favourable prognostic tumours which was not statistically significant. There was no association between recurrence risk and lymphangiogenic marker expression.

Conclusion

In summary, the findings from this study show that lymphangiogenesis, measured by specific lymphatic marker expression, is higher in breast cancers than in normal breast tissue. Secondly, breast cancers which have metastasised to the regional lymphatics show higher expression compared to those which have not, although the individual differences for all five markers were not statistically significant.