Elsevier

Human Pathology

Volume 38, Issue 2, February 2007, Pages 247-259
Human Pathology

Original contribution
Accurate assessment of lymph vessel tumor emboli in invasive ductal carcinoma of the breast according to tumor areas, and their prognostic significance

https://doi.org/10.1016/j.humpath.2006.07.017Get rights and content

Summary

Lymph vessel tumor emboli (LVTEs) within tumors are difficult to distinguish from stroma-invasive tumor foci. The purpose of this study was to evaluate staining of LVTEs with hematoxylin-eosin (HE) and with D2-40 to determine whether LVTEs identified by HE staining alone are D2-40–positive LVTE and whether the presence of LVTE identified by HE or D2-40 staining is an accurate predictor of outcome in 151 patients with invasive ductal carcinoma (IDC) of the breast. We first attempted to identify LVTE in the stroma-invasive tumor area (intratumor area), the advance area, and the nontumor area by HE staining alone, and then LVTE identified by HE staining was confirmed by D2-40 staining. The number of LVTE identified by HE staining and D2-40 staining successively increased from the intratumor area to the nontumor area. Although D2-40 staining detected larger numbers of LVTE than HE staining in all tumor areas, the highest positive predictive value of LVTE was observed in the intratumor area, and the next was in the advance area, and then the nontumor area, and significant correlations were found between the numbers of LVTE stained by HE and D2-40 in the same tumor areas. LVTE identified by HE staining or D2-40 staining in the intratumor area or nontumor area significantly increased the risk for tumor recurrence or death of patients with IDC, independent of hormone receptor status or nodal status. The results of this study demonstrate that the existence of intratumoral LVTE and that the presence of intratumoral LVTE identified by HE staining or D2-40 staining are accurate predictors of the outcome of patients with IDC of the breast.

Introduction

Artifactual spaces often form around the nests of stroma-invasive tumor cells within an invasive carcinoma as a result of tissue shrinkage during processing, making it very difficult to distinguish the artifacts from true intratumoral lymph vessel spaces. As a result, pathologists generally examine tumors for the presence of lymph vessel tumor emboli (LVTEs) at or beyond the border of the stroma-invasive tumor area. However, because lymph vessels within the invasive tumor area are surrounded by many stroma-invasive tumor cells that may give rise to nodal or lymphogenous distant organ metastasis, the detection of LVTEs in the invasive tumor area has a very important prognostic significance in patients with breast carcinoma.

Several putative lymphatic endothelial markers have recently been proposed [1], [2], [3], [4], [5], and D2-40 is a novel monoclonal antibody to an Mr 40 000 O-linked sialoglycoprotein that reacts with a fixation-resistant epitope on the lymphatic endothelium. It does not stain the endothelium of blood vessels, including arteries, veins, and capillaries, and its usefulness for detecting intratumoral lymph vessels has been reported in several tumors [6], [7], [8], [9], [10], [11].

The purpose of this study was to evaluate (1) whether LVTEs exist within the stroma-invasive tumors of invasive ductal carcinomas (IDCs) of the breast, (2) whether LVTEs identified by hematoxylin-eosin (HE) staining alone in stroma-invasive tumor area and LVTEs at or beyond the border of the stroma-invasive tumor area are true LVTEs, and (3) whether the presence of LVTEs identified by HE or D2-40 staining or D2-40 lymph vessel density is an accurate predictor of nodal metastasis or the outcome of patients with IDC. The results showed that intratumoral LVTEs do exist, and that the presence of intratumoral LVTEs identified by HE or D2-40 staining is an important accurate predictor of the outcome of patients with IDC of the breast.

Section snippets

Cases

The subject of this study was 151 consecutive cases of IDC of the breast surgically treated at the National Cancer Center Hospital East, Chiba, Japan, between 1993 and 1995. Clinical information was obtained from the patients' medical records after complete histologic examination of all IDCs. All patients were Japanese women, and they ranged from 28 to 84 years old (mean age, 53 years). All patients had a solitary lesion. There were no cases of inflammatory breast cancer in this series.

For

Maximum, minimum, median, and mean numbers of LVTEs identified by HE staining and D2-40 staining according to tumor area

The largest number of cases in which an LVTE was detected by HE or D2-40 staining was observed in the advance area, and the smallest number of cases that had an LVTE was observed in the intratumor area (Table 1). The highest maximum number of LVTEs identified by HE or D2-40 staining was in the nontumor area, and it was followed by the advance area and then the intratumor area, and the mean numbers of LVTEs showed a similar tendency.

The highest maximum D2-40 lymph vessel density was in the

Discussion

The results of this study clearly demonstrated that LVTEs were actually present in the intratumor area of IDCs and that the cumulative numbers of LVTEs identified by HE staining and D2-40 staining gradually increased from the intratumor area to the nontumor area. Indeed, LVTEs were detected by staining with D2-40 in each tumor area that were not detected by HE staining alone, for example, approximately 60% of IDC LVTEs in the intratumor area. However, the results of this study also clearly

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