Lymphangiogenesis and lymph node metastasis in breast cancer.
BACKGROUND
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.


CONCLUSIONS
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.
Cunnick
Giles H
GH
Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff, CF14 4XN, Wales, UK. Giles.Cunnick@buckshosp.nhs.uk
Jiang
Wen G
WG
Douglas-Jones
Tony
T
Watkins
Gareth
G
Gomez
Kelvin F
KF
Morgan
Mike J
MJ
Subramanian
Ashok
A
Mokbel
Kefah
K
Mansel
Robert E
RE
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism
D014408:Biomarkers, Tumor; D012333:RNA, Messenger