Significance of lymph vessel invasion identified by the endothelial lymphatic marker D2-40 in node negative breast cancer

Abstract

Monoclonal antibody D2-40, a marker of lymphatic endothelium, identifies tumor emboli in lymph vessels. The aim of the study was to assess whether D2-40 þ lymph vessel invasion (LVI) correlates with clinicopathologic factors including lymphovascular invasion (LVI) as assessed by haematoxylin and eosin-stained sections (H&E þ or H&EÀ) and to assess the prognostic significance in node-negative breast cancer. The study group consisted of 303 node-negative breast cancer patients that had a median follow-up of 7.6 years. Clinical and pathological data were retrieved from the Henrietta Banting database. Immunohistochemical staining was performed on formalin-fixed, paraffin-embedded tissue sections of the primary invasive carcinoma using D2-40. Immunostaining with CD31 was performed on the discordant cases that were H&E þ /D2-40À. D2-40 þ lymph vessel invasion was detected in 82/303 (27%) cases. The foci of lymphatic invasion occurred predominantly at the invasive front of the tumor. The absence of D2-40 and CD31 in 13/17 discordant cases was suggestive of retraction artefact. D2-40 þ lymph vessel invasion correlated significantly with age (P ¼ 0.0003), tumor size (P ¼ 0.005), histological grade (P ¼ 0.0001), H&E þ (P ¼ o0.0001) and estrogen receptor status (P ¼ 0.005) but not with histological type or progesterone receptor status. Multivariate analysis revealed that D2-40 þ lymph vessel invasion was the only significant predictor of distant recurrence. There was no significant association between D2-40 status and local recurrence (P ¼ 0.752) or regional recurrence (P ¼ 0.13). Both D2-40 þ lymph vessel invasion (P ¼ 0.009) and H&E þ LVI cases (P ¼ 0.02) were associated with overall shorter survival in univariate analysis. These data indicate that D2-40 identifies lymphatic invasion in breast tumors and is a significant predictor of outcome in breast cancer.

Is it useful to detect lymphovascular invasion in lymph node‐positive patients with primary operable breast cancer?

“…[2][3][4][5] Recently, it has been shown that immunostaining, especially with D2-40, may be useful to detect missed H & E LVI. 10,11 In a previous work on lymph node-negative tumors, we also observed that D2-40 increases the diagnostic sensitivity of LVI by a factor of 1.4, and strengthens the prognostic impact of this factor. 9 As only peritumoral LVI has prognostic significance, this analysis cannot be easily performed on tissue microarray blocks.…”

D2-40/p63 defined lymph vessel invasion has additional prognostic value in highly proliferating operable node negative breast cancer patients

“…For survival analysis, the main end points were distant metastases recurrence, and overall distant metastases-related survival (a previous study on node negative patients showed that lymph vessel invasion was only prognostic for distant metastases 11 ). To determine the probability that patients would remain free of distant metastases, we defined recurrence as any first recurrence at a distant site.…”

“…The monoclonal antibody D2-40 has often been used as a marker of lymphatic endothelium to identify tumor emboli in lymph vessels. 11 However, D2-40 does not only stain lymph vessels but also breast myopethelial cells (Figure 1). The growth pattern of tumor cells surrounded by D2-40-positive myoepitelial cells generally enables distinction of ductal carcinoma in situ from lymphovascular invasion.…”

Incomplete inside-out growth pattern in invasive breast carcinoma: association with lymph vessel invasion and recurrence-free survival

“…Invasion of tumor cells into lymphatic vessels is a critical step in metastasis, and lymph vessel invasion (LVI) is a predictor for axillary lymph node metastasis and a prognostic factor in node-negative cancer [2][3][4][5][6][7][8]. LVI can also be used to determine the appropriate indications for chemotherapy [7][8][9].…”