14 research outputs found
Lymphatic expression of CLEVER-1 in breast cancer and its relationship with lymph node metastasis
BACKGROUND
Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1) in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process.
METHODS
148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC), CD209 (immature DC, iDC) and CD68 (macrophage, MÏ•). In vitro expression of CLEVER-1 on lymphatic (LEC) and blood endothelial cells (BEC) was examined by flow cytometry.
RESULTS
In vitro results showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples), lymphatic vessels (LV, 18.2% of samples) and in MÏ•/DCs (82.4% of samples). However, only CLEVER-1 expression in LV was associated with LN metastasis (p = 0.027) and with MÏ• indices (p = 0.021). Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p = 0.049). The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p < 0.001) and LV (p = 0.004).
CONCLUSIONS
The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN
Oestrogen receptor negative early operable primary breast cancer in older women—biological characteristics and long-term clinical outcome
BackgroundOlder women are at the greatest risk of breast cancer development and a considerable number present with comorbidities. Although the majority of breast cancers in this age group express oestrogen receptor (ER), which makes endocrine therapy (primary or adjuvant) feasible, given the huge size of the elderly population, there remains a significant number of patients, in absolute term, whose tumours do not express ER and their management is challenging.MethodsOf a consecutive series of 1,758 older (≥70 years) women with early operable primary breast cancer managed in a dedicated service from 1973–2010, 252(14.3%) had ER-negative (histochemical (H) score ≤50) tumours. Their clinical outcome was retrospectively reviewed and tumour samples collected from diagnostic core biopsies were analysed for progesterone receptor (PgR), HER2 and Ki67 using immunohistochemistry.ResultsThe commonest primary treatment was surgery (N = 194, 77%) followed by primary endocrine therapy (14.3%), primary radiotherapy (5.6%) and supportive treatment only (3.1%). Among the patients undergoing surgery, most of them had grade 3 (78.1%) and node-negative disease (62.2%). Some of them (21.1%) received postoperative radiotherapy. At a median follow-up of 37.5 months, 117 patients had died, out of which 48.6% were due to breast cancer. For those who underwent surgery, the regional and local recurrence rates were 2% and 1.1% per annum respectively. For those who received primary endocrine therapy, 38% progressed at 6 months, however all patients who had primary radiotherapy achieved clinical benefit at 6 months. Regardless of treatment given, the 5-year breast cancer specific and overall survival rates were 70% and 50% respectively. Biological analysis based on good quality needle core biopsy specimensfrom181 patients showed that 26.8% (N = 49), 16.9% (N = 31) and 70.7% (N = 70)expressed positivity for PgR, HER2 and Ki67 respectively. No correlation between these biomarkers and breast cancer specific survival was demonstrated.ConclusionOestrogen receptor negative early operable primary breast cancer in older women is associated with poor prognostic features in terms of biology and clinical outcome. Surgery appears to produce the best outcome as a primary treatment, however for those where neither surgery nor chemotherapy is appropriate, primary radiotherapy can be beneficial
Lymphatic and angiogenic characteristics in breast cancer: morphometric analysis and prognostic implications
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
Lymphatic expression of CLEVER-1 in breast cancer and its relationship with lymph node metastasis
BACKGROUND
Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1) in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process.
METHODS
148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC), CD209 (immature DC, iDC) and CD68 (macrophage, MÏ•). In vitro expression of CLEVER-1 on lymphatic (LEC) and blood endothelial cells (BEC) was examined by flow cytometry.
RESULTS
In vitro results showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples), lymphatic vessels (LV, 18.2% of samples) and in MÏ•/DCs (82.4% of samples). However, only CLEVER-1 expression in LV was associated with LN metastasis (p = 0.027) and with MÏ• indices (p = 0.021). Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p = 0.049). The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p < 0.001) and LV (p = 0.004).
CONCLUSIONS
The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN
Patient and tumour characteristics and management pattern of ER-negative early operable primary breast cancer in older women.
<p>Patient and tumour characteristics and management pattern of ER-negative early operable primary breast cancer in older women.</p
Clinical outcome and expression of biomarkers in ER-negative versus ER-positive tumours in older women with early operable primary breast cancer.
<p>Clinical outcome and expression of biomarkers in ER-negative versus ER-positive tumours in older women with early operable primary breast cancer.</p
Kaplan-Meier plots of time-dependant outcome variables in older women with ER-negative early operable primary breast cancer.
<p>(A) Breast cancer specific survival of Oestrogen receptor negative early operable primary breast cancer in older women. (B) Overall survival of Oestrogen receptor negative early operable primary breast cancer in older women. (C) Local recurrence free survival of Oestrogen receptor negative early operable primary breast cancer in older women- Mastectomy versus wide local excision. (D) Regional recurrence free survival of Oestrogen receptor negative early operable primary breast cancer in older women- Axillary surgery versus no axillary surgery. (E) Breast cancer specific survival of Oestrogen receptor negative early operable primary breast cancer in older women- Progesterone Receptor (PR) positive versus negative. (F) Breast cancer specific survival of Oestrogen receptor negative early operable primary breast cancer in older women- Human Epidermal Growth Factor Receptor– 2 (HER2) positive versus negative. (G) Breast cancer specific survival of Oestrogen receptor negative early operable primary breast cancer in older women- Ki67 positive versus negative. (H) Breast cancer specific survival of Oestrogen receptor negative early operable primary breast cancer in older women- Low (ie 1–2) Grade versus high (ie 3) Grade.</p
Summary of patients with ER-negative early operable primary breast cancer treated by primary radiotherapy.
<p>Summary of patients with ER-negative early operable primary breast cancer treated by primary radiotherapy.</p