D2-40 in breast cancer: should we detect more vascular emboli?

Abstract

Peritumoral emboli assessed on hematoxylin-eosin-stained slides are taken into account for treatment of patients with operable breast cancer. We assessed whether immunostaining with D2-40 improves the prognostic significance of emboli in a group of tumors with a large immunohistochemical sampling and a longterm follow-up. Topography, number, and extension of hematoxylin-eosin and D2-40 emboli were compared in 94 node-negative breast cancers (median number of immunostained slides per tumor: 3). Metastatasis-free survival of patients with or without hematoxylin-eosin and/or D2-40 emboli were evaluated (median follow-up of 178 months). Hematoxylin-eosin emboli were detected in 14 (15%) tumors and were located at distance from the tumor. D2-40 emboli were detected in 39 (41%) tumors and was often multiple (n ¼ 30), extensive (n ¼ 23), located within (n ¼ 13), close to (n ¼ 10) or at distance from the tumor (n ¼ 16). The 12 distant hematoxylin-eosin and D2-40 emboli were located in the same vessels (seven missed at the first hematoxylin-eosin examination and secondarily diagnosed by D2-40 staining). A difference in metastasis-free survival was found only between patients with no D2-40 emboli and those with distant D2-40 emboli (P ¼ 0.02). D2-40 emboli located within or close to the tumor had no prognostic value. Comparing the metastasis-free survival of patients with or without hematoxylin-eosin emboli, the prognostically unfavorable significance of hematoxylin-eosin emboli was improved when taking into account the seven patients with missed emboli at the first examination and secondarily diagnosed by D2-40 staining (P ¼ 0.006 vs 0.003). To conclude, D2-40 increases the diagnostic sensitivity of emboli in breast carcinoma and the high incidence of D2-40 emboli might be related to the number of immunostained slides per case. Nevertheless, only distant D2-40 þ emboli had a prognostic impact. In practice, D2-40 might be useful to detect missed hematoxylin-eosin emboli especially in cases without any other prognostically unfavorable criterion.

Determinants of lymph node status in women with breast cancer

“…LVI was assessed on HE stained slides, as defined by Rosen and Oberman7. Tumour cell emboli within endothelium-lined vascular spaces are seen on HE stained slides of the breast cancer8.…”

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

“…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. It may be anticipated that such complementary analysis would also give similar results in lymph node-positive tumors.…”

“…1), in the breast surrounding invasive carcinoma, that is, separated from the tumor by normal breast tissue and often next to a small artery or vein. 1,8,9 When H & E LVI was suspected in the vicinity of the tumor, differential diagnosis with an artifact (retraction) was difficult, and such equivocal cases were recorded as negative. In our study, only unequivocal H & E LVI was prospectively recorded as positive without distinguishing blood vessels from lymphatics.…”

The Role of Lymphovascular Invasion as a Prognostic Factor in Patients with Lymph Node-Positive Operable Invasive Breast Cancer

“…Lymphovascular invasion (LVI) is defined as tumor emboli present within a definite endothelial-lined space in the breast surrounding invasive carcinoma [6,7]. The existence of LVI may help identify who is at increased risk for axillary lymph node and distant metastasis [2,3] Although LVI has been accepted as an important prognostic factor in patients with lymph node-negative invasive breast cancer [8], LVI is controversial regarding prognostic value in patients with lymph node-positive breast cancer [3,9-11].…”