Table 1.

Association of lymphatic vessel invasion (LVI) with lymphatic metastasis in breast cancer

# of Patients	Method of Analysis	Comments	P value^a	Reference
4,351	H&E^b	Sentinel LN^b metastasis was strongly associated with peritumoral vascular invasion (pVI)	P<0.0001	[37]
2,606	H&E	LN metastasis significantly correlated with perivascular invasion encompassing both LVI^b or BVI^b	P<0.0001	[110]
850	H&E	LVI detected in 51% of patients was the most significant predictor for axillary LN metastases	P<0.001	[51]
400	IHC^b	Patients with LVI were more likely to have sLN^b metastases (51.3% of LVI-positive patients had positive sLN)	P<0.001	[46]
374	IHC	LVI was significantly associated with a higher risk for developing lymph node metastasis	P=0.004	[50]
254	H&E and IHC	In a multivariate analysis, LVI was the strongest predictor for ALNM^b with an odds ratio of 3.489	P=0.0003	[41]
206	H&E	LVI was significantly associated with non-sentinel LN involvement (41% of LVI-positive patients had also positive LN versus 26% of LVI-negative patients)	P=0.021	[230]
194	H&E and IHC	Strong association was found between pLVI and non-sentinel LN metastasis (65% versus 37%)	P=0.001	[231]
177	IHC	LVI was strongly associated with LN metastasis, distant metastasis, decreased disease-free interval and overall survival	P<0.001	[36]
165	H&E	LVI in the primary tumor was the only factor significantly associated with metastases in the non-sentinel LN	P<0.01	[45]
123	IHC	LVI but not BVI significantly correlated with lymphatic metastasis	P=0.002	[42]
118	H&E	LVI was a strong predictor of axillary LN metastasis regardless of tumor size	P<0.0001	[232]
113	IHC	LVI correlated with LN metastasis, LVD^b and VEGF-C^b	P< 0.0001	[70]
98	IHC	LVI correlated with VEGF-C, which was expressed in ~40% of breast cancers but not in adjacent normal mammary glands	P=0.0004	[67]
95	H&E and IHC	Only peritumoral LVI, but not BVI, was associated with LN metastases. LVI exceeded BVI in both the number of invaded vessels and the size of the emboli. (P=0.004)	P=0.002	[44]

P value indicates association of intratumoral or peritumoral lymphatic vessel invasion with LN metastasis.

Abbreviations: H&E, hematoxylin & eosin; LN, lymph node; LVI, lymphatic vascular invasion; BVI, blood vascular invasion; IHC, immunohistochemistry; sLN, sentinel lymph node; pLVI, peritumoral lymphatic vascular invasion; DFS, disease-free survival; OS, overall survival; ALNM, axillary lymph node metastasis; LEC, lymphatic endothelial cells; LVD, lymphatic vessel density; VEGF-C, vascular endothelial growth factor C.