Van den Eynden Gert G, Vandenberghe Melanie K, van Dam Pieter-Jan H, Colpaert Cecile G, van Dam Peter, Dirix Luc Y, Vermeulen Peter B, Van Marck Eric A
Translational Cancer Research Group (Lab Pathology, University of Antwerp/University Hospital Antwerp, Wilrijk; Oncology Center, General Hospital St.-Augustinus, Wilrijk, Belgium), Antwerp, Belgium.
Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5391-7. doi: 10.1158/1078-0432.CCR-07-1230.
Lymph node (LN) lymphangiogenesis has recently been shown to be important in the premetastatic niche of sentinel LNs. To study its role in the further metastatic spread of human breast cancer, we investigated the association of angiogenesis and lymphangiogenesis in sentinel LN metastases with the presence of nonsentinel LN metastases in breast cancer patients with a positive sentinel LN.
Angiogenesis and lymphangiogenesis--quantified as endothelial cell proliferation fraction (ECP%) and lymphatic ECP fraction (LECP%)--were assessed in sentinel LN metastases of 65 T(1)/T(2) patients with breast cancer using CD34/Ki67 and D2-40/Ki67 immunohistochemical double stains. Correlations were analyzed between nonsentinel LN status, LECP%, and other clinicopathologic variables (number of involved sentinel LNs, size of the primary tumor and LN metastasis, presence of lymphovascular invasion in the primary tumor, and of extracapsular growth in the sentinel LN metastasis).
Thirty seven out of 65 patients (56.9%) had at least one involved nonsentinel LN. Size of the sentinel LN metastasis (P = 0.001), lymphovascular invasion (P = 0.02), extracapsular growth (P = 0.02), and LECP% (P = 0.01) were correlated with a positive nonsentinel LN status. The multivariate logistic regression model retained high LECP% (odds ratios = 4.2, P = 0.01) and the presence of extracapsular growth (odds ratios = 3.38, P = 0.04) as independently associated with the presence of nonsentinel LN metastases.
Increased sentinel LN metastasis lymphangiogenesis is associated with metastatic involvement of nonsentinel axillary LNs. These are the first data sustaining the hypothesis that sentinel LN lymphangiogenesis is involved in further metastatic spread of human breast cancer.
最近研究表明，前哨淋巴结（SLN）的淋巴管生成在其前哨转移微环境中起着重要作用。为研究其在人类乳腺癌进一步转移扩散中的作用，我们调查了前哨淋巴结转移中血管生成和淋巴管生成与前哨淋巴结阳性的乳腺癌患者非前哨淋巴结转移的关系。
采用CD34/Ki67和D2-40/Ki67免疫组化双重染色法，对65例T(1)/T(2)期乳腺癌患者的前哨淋巴结转移中的血管生成和淋巴管生成（以内皮细胞增殖分数（ECP%）和淋巴管ECP分数（LECP%）量化）进行评估。分析非前哨淋巴结状态、LECP%与其他临床病理变量（受累前哨淋巴结数量、原发肿瘤和淋巴结转移大小、原发肿瘤中淋巴管侵犯情况以及前哨淋巴结转移中的包膜外生长情况）之间的相关性。
65例患者中有37例（56.9%）至少有一个受累非前哨淋巴结。前哨淋巴结转移大小（P = 0.001）、淋巴管侵犯（P = 0.02）、包膜外生长（P = 0.02）和LECP%（P = 0.01）与非前哨淋巴结阳性状态相关。多因素逻辑回归模型显示，高LECP%（优势比 = 4.2，P = 0.01）和包膜外生长的存在（优势比 = 3.38，P = 0.04）与非前哨淋巴结转移的存在独立相关。
前哨淋巴结转移中淋巴管生成增加与腋窝非前哨淋巴结的转移受累相关。这些是支持前哨淋巴结淋巴管生成参与人类乳腺癌进一步转移扩散这一假说的首批数据。
