Lack of lymphangiogenesis during breast carcinogenesis

Abstract

Background: Recent evidence suggests that functional intratumorous lymph vessels may be absent from some human cancers. This could result from either the failure of tumours to induce lymphangiogenesis, or the collapse of lymph vessels, caused by high interstitial tumour pressure.

Methods: To differentiate between these two hypotheses, paraffin wax embedded clinical specimens from normal breast (n = 13), usual ductal hyperplasia (n = 11), ductal carcinoma in situ (n = 21), and invasive breast cancer (n = 40) were compared for lymphatic and blood vessel density by immunohistochemistry with antibodies to the lymphatic endothelial hyaluronan receptor (LYVE-1) and CD31, respectively.

Results: Lymph vessel density was lower than blood vessel density in normal breast tissue. Within breast lobuli, lymph vessels were absent. In premalignant lesions blood microvessel density increased, whereas no increase in lymph vessels could be seen intralesionally. In invasive cancers, lymph vessels were absent in all but a few cases, where probably some pre-existing lymph vessels remained, although blood microvessel density was once again increased.

Conclusion: Unlike angiogenesis, lymphangiogenesis is absent during breast carcinogenesis. This, and not rising interstitial pressure caused by an increase in the size of lesions, explains the absence of intratumorous lymph vessels in invasive breast cancer.

Figure 1

Lymph and blood vessel patterns in the normal human breast, premalignant lesions, and invasive breast cancer. (A) In the normal breast, scattered lymph vessels are seen in the interlobular stroma. No intralobular lymph vessels are seen. Arrow: unstained blood vessel associated with lymph vessels. (B) In the normal breast, numerous blood vessels are seen, also in the intralobular space. (C) Lymph vessels are present at some distance in the adipose tissue surrounding usual ductal hyperplasia. (D) Ductal carcinoma in situ with lymph vessels in the surrounding stroma at some distance from the neoplastic ducts. (E) Blood vessels are present as a vascular rim around a ductal carcinoma in situ. (F) In invasive breast cancer, lymphatics are seen at the tumour margin, but are absent from the intratumorous stroma in most cases. (G) In invasive breast cancer, intratumorous lymphatics are seen occasionally in the intratumorous stroma in some cases. (H) In invasive breast cancer, intratumorous blood vessels are dispersed within the tumour.