Lymphatic and blood vessels in basal and triple-negative breast cancers: characteristics and prognostic significance

Abstract

Basal and triple-negative breast cancer phenotypes are characterised by unfavourable biological behaviour and outcome. Although certain studies have examined their pathological and molecular profile, the vascular characteristics of lymphatic and blood vessels have not been examined. Immunohistochemical staining with podoplanin, CD34 and CD31 was used to examine lymphatic and microvessel density, as well as vascular invasion in 197 basal-like and in 99 triple-negative breast tumours and compared against 200 non-basal and 334 non-triple-negative cases. All specimens were lymph node negative. Vascular invasion was identified as blood or lymphatic vascular invasion by the differential expression of markers. All measurements were correlated with clinicopathological features and prognosis. No significant difference was detected between the basal and triplenegative groups in terms of lymphatic or microvessel density or vascular invasion. However, both the basal and the triple-negative groups showed significantly higher microvessel density than did the non-basal and non-triple-negative groups (P ¼ 0.017 and Po0.001, respectively). Unlike microvessel density, no significant difference was detected in lymphatic density between the basal or triple-negative groups compared with their respective controls. Interestingly, vascular invasion, almost entirely lymphatic invasion, was detected in 27% of the basal and in 26% of the triple-negative groups with no significant difference in comparison with control groups. In both basal and triple negatives, vascular invasion was associated with poorer survival by univariate and multivariate analyses. The 20-year overall survival rate in basal-like tumours was 55% in vascular invasionpositive cases compared with 73% in vascular invasion-negative tumours (P ¼ 0.012), and 46% in triple-negative vascular invasion-positive compared with 79% in vascular invasion-negative tumours (P ¼ 0.001). Basal-like vs non-basal-like and triple-negative vs non-triple-negative tumours have similar vascular characteristics in terms of lymphatic vessel density and vascular invasion but higher microvessel density, suggesting that such groups may preferentially benefit from anti-angiogenic therapy. Vascular invasion was, in all phenotypes, almost entirely lymphatic vessel invasion and could stratify basal-like and triple-negative phenotypes into distinct prognostic groups.

Lymphangiogenesis assessed using three methods is related to tumour grade, breast cancer subtype and expression of basal marker

“…Other researchers found them in 85% of studied cases [6]. The range of LVD found in our study (0-21.1) was similar to ranges reported by other authors (0-10.57 [12], 0-31 [13], 0-45 [6]). Additional parameters evaluated in this study (DPV, LVD/ MVD) are presented for the first time.…”

“…Moreover, expression of this marker was noted in myoepithelial cells and in stromal cancer-associated fibroblasts, what is in accordance with other authors studies [2][3][4][5][6][7][8][9][12][13][14][15][16][17]. Selected vessels were double-stained with CD34 and podoplanin.…”

“…Authors who reported a relation between lymphatic vessel density and lymph node metastases or other clin-ico-pathological parameters applied the method recommended by Weidner et al or used the "Chalkley count" [6,[10][11][12][13][14][15]. Both methods are based on immunohistochemical visualization of blood vessels using specific endothelial markers (e.g.…”

“…In the first method [10] the assessment of microvessel density is carried out with a light microscope in a single area with the highest microvessel density. Whereas in the "Chalkley count" technique the fixed dots of an eyepiece graticule (12-point), that come into contact with CD31-stained tissue are recorded instead of counting individual microvessels [11,12]. The above-mentioned technique examines the relative area occupied by microvessels rather than the true vessel count [11,12].…”

Prognostic significance of lymphatic invasion in lymph node-positive breast carcinoma: findings from a large case series with long-term follow-up using immunohistochemical endothelial marker

“…More information about vascular characteristics and LI in basal and triple-negative BC was reported in a previous study. 17 LI occurred at significantly higher rate with higher expression of HER-2. LI positivity was 71% in HER-2-positive immunohistochemistry score 3 group compared with 45% in HER-2 score 0 group (P ¼ 0.006).…”