Tumour lymphangiogenesis is a possible predictor of sentinel lymph node status in cutaneous melanoma: a case-control study.
BACKGROUND
Cutaneous melanoma spreads preferentially through the lymphatic route and sentinel lymph node (SLN) status is regarded as the most important predictor of survival.


OBJECTIVE
To evaluate whether tumour lymphangiogenesis and the expression of vascular endothelial growth factor C (VEGF-C) is related to the risk of SLN metastasis and to clinical outcome in a case-control series of patients with melanoma.


METHODS
Forty five invasive melanoma specimens (15 cases and 30 matched controls) were investigated by immunostaining for the lymphatic endothelial marker D2-40 and for VEGF-C. Lymphangiogenesis was measured using computer assisted morphometric analysis.


RESULTS
Peritumorous lymphatic vessels were more numerous, had larger average size, and greater relative area than intratumorous lymphatics. The number and area of peritumorous and intratumorous lymphatics was significantly higher in melanomas associated with SLN metastasis than in non-metastatic melanomas. No significant difference in VEGF-C expression by neoplastic cells was shown between metastatic and non-metastatic melanomas. Using logistic regression analysis, intratumorous lymphatic vessel (LV) area was the most significant predictor of SLN metastasis (p = 0.04). Using multivariate analysis, peritumorous LV density was an independent variable affecting overall survival, whereas the intratumorous LV area approached significance (p = 0.07).


CONCLUSIONS
This study provides evidence that the presence of high peritumorous and intratumorous lymphatic microvessel density is associated with SLN metastasis and shorter survival. The intratumorous lymphatic vessel area is the most significant factor predicting SLN metastasis. The tumour associated lymphatic network constitutes a potential criterion in the selection of high risk patients for complementary treatment and a new target for antimelanoma therapeutic strategies.
Massi
D
D
Department of Human Pathology and Oncology, University of Florence, I-50134 Florence, Italy. Daniela.Massi@UNIFI.IT
Puig
S
S
Franchi
A
A
Malvehy
J
J
Vidal-Sicart
S
S
González-Cao
M
M
Baroni
G
G
Ketabchi
S
S
Palou
J
J
Santucci
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D016019:Survival Analysis; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
D009363:Neoplasm Proteins; D042582:Vascular Endothelial Growth Factor C