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

Abstract

The poor prognostic significance of lymphatic invasion (LI) in breast carcinoma (BC) as a whole and in lymph node (LN)-negative patients in particular has been recognized in several studies; however, its prognostic role in LN-positive patients is still questionable. Aim of the current study was to assess prognostic role of LI in LN-positive BC specimens. Sections from non-selected 557 LN-positive BC specimens were stained with antibody to podoplanin/D2-40. LI was identified and correlated with clinicopathological features and patients' outcome. Twenty-year overall survival (OS), disease-free interval (DFI), and development of distant metastasis (DM) or recurrence were known for all patients. LI was detected in 262/557 (47%) of specimens ranging from 1 to 350 lesion per tumor section. Its presence was associated with higher grade tumors (Po0.0001), negative hormonal receptors (Po0.0001), high HER-2 expression (P ¼ 0.006), and with increased number of positive LNs (P ¼ 0.019). In the whole LN-positive BC, presence of LI was a poor prognostic factor for OS, DFI, and development of DM both in univariate and in multivariate analysis. In further stratification of patients, LI was associated with poorer prognosis in patients with single positive LN and not in patients with 41 positive LN. In T1N1 stage, LI was highly associated with poor OS (P ¼ 0.002), DFI (Po0.0001), and DM (Po0.0001). In T2N1 patients, LI was associated only with poorer DFI (P ¼ 0.037) but not with death or DM. In the two former patient groups, LI lost significance in multivariate analysis. In conclusion, LI is a poor prognostic factor in LN-positive BC particularly for patients having single positive LN. LI therefore would add further prognostic significance when considered in treatment in those patients. We recommend incorporation of LI in breast carcinoma staging and in prognostic indices.

High lymphatic vessel density and presence of lymphovascular invasion both predict poor prognosis in breast cancer

“…On the other hand, 11studies [13, 14, 18, 20, 25–31], involving 3070 patients (sample sizes ranged from 48 to1005), were eligible to evaluate the prognostic value of lymphovascular invasion (Table 2). All of the included studies used the presence of lymphovascular invasion to evaluate its prognostic value.…”

“…It means that the cutoff value is defined as the presence or not of lymphovascular invasion. And nine of them reported the detection rate of lymphovascular invasion in breast cancer [13, 14, 20, 25–28, 30, 31]. The detection rates were ranged from 21.2 to 47.0%, with an overall detection rate of 29.56% (827/2798).…”

“…However, the result should be analysed more thoroughly. Mohammed et al [14, 31] has demonstrated that the impact of lymphovascular invasion is mainly found in breast cancer patients with negative lymph node metastasis and with a single positive lymph node metastasis. Moreover, the frequency of lymphovascular invasion per tumor lesion has no effects on prognosis in lymph node negative and lymph node positive patients [14, 31].…”

“…Mohammed et al [14, 31] has demonstrated that the impact of lymphovascular invasion is mainly found in breast cancer patients with negative lymph node metastasis and with a single positive lymph node metastasis. Moreover, the frequency of lymphovascular invasion per tumor lesion has no effects on prognosis in lymph node negative and lymph node positive patients [14, 31]. Besides, the location of lymphovascular invasion [23, 30] and the patients’ age [25] also have influence on the survival of breast cancer patients.…”

“…At present, lymphatic vessels can be distinguished from blood vessels or retraction artifacts. Thus, using immunohistochemical staining, many studies have updated the investigation of the prognostic value of lymphovascular invasion [13, 14]. …”