Department of Surgery, Upper GI Research Unit, Medical University of Vienna, Cancer Comprehensive Center Vienna GET, Vienna, Austria.
Surgery. 2013 Apr;153(4):526-34. doi: 10.1016/j.surg.2012.10.007. Epub 2013 Jan 4.
Tumor-associated lymphatic networks are the primary routes for tumor cell dissemination and metastasis. Behind the background of possible lymphangiogenesis-associated therapies, the clinical impact of lymphangiogenesis (measured by lymphatic microvessel density [LMVD]) and specific lymphovascular invasion (LVI) in esophageal cancer remains unclear. The aim of this study was to evaluate the clinical role of lymphangiogenesis and LVI in a large cohort of esophageal cancer.
For the specific assessment of LMVD and LVI, 393 tissue samples from a prospective tissue databank of esophageal adenocarcinomas, squamous cell carcinomas, and their precursor lesions were included into this study. LMVD and LVI were assessed by immunostaining for podoplanin, a selective marker of lymphatic endothelium. In addition the peritumoral inflammatory stroma reaction (ISR) was assessed.
Patients with high LMVD had a significant increased risk to develop LVI (P = .00123; coefficient of regression [CR] 0.27) and lymph node metastasis (P = .00233), independent of the tumor's histology. During a follow-up of 52 months, patients with high LMVD had a significantly reduced overall survival (OS; P < .001; 5-year OS 30% vs 54%) and disease-free survival (DFS; P < .001; 5-year DFS 28% vs 48%). OS (P < .001; 5-year OS 14% vs 60%) and DFS (P < .001; 5-year DFS 14% vs 49%) were significantly reduced in patients with present LVI. In invasive cancer, LMVD was significantly increased compared with precursor lesions (P = .008). The amount of ISR correlated significantly with LMVD.
Our data provide evidence for a clinically significant role of specific lymphangiogenesis in esophageal cancer. Patients with high lymphangiogenic tumor activity represent candidates for lymphangiogenesis-associated therapies.
肿瘤相关的淋巴管是肿瘤细胞扩散和转移的主要途径。在可能与淋巴管生成相关的治疗背景下，食管癌中淋巴管生成（通过淋巴管微血管密度[LMVD]测量）和特定的淋巴血管侵犯（LVI）的临床影响仍不清楚。本研究旨在评估淋巴管生成和 LVI 在大型食管癌队列中的临床作用。
为了专门评估 LMVD 和 LVI，本研究纳入了来自食管腺癌、鳞状细胞癌及其前体病变的前瞻性组织数据库的 393 个组织样本。通过免疫组化染色检测淋巴管内皮细胞的特异性标志物 podoplanin 来评估 LMVD 和 LVI。此外，还评估了肿瘤周围炎症性基质反应（ISR）。
LMVD 较高的患者发生 LVI（P =.00123；回归系数[CR]0.27）和淋巴结转移的风险显著增加（P =.00233），这与肿瘤的组织学无关。在 52 个月的随访期间，LMVD 较高的患者总生存率（OS；P <.001；5 年 OS 为 30% vs 54%）和无病生存率（DFS；P <.001；5 年 DFS 为 28% vs 48%）显著降低。存在 LVI 的患者 OS（P <.001；5 年 OS 为 14% vs 60%）和 DFS（P <.001；5 年 DFS 为 14% vs 49%）显著降低。与前体病变相比，侵袭性癌中的 LMVD 显著增加（P =.008）。ISR 的数量与 LMVD 显著相关。
本研究数据提供了食管癌中特定淋巴管生成具有临床显著作用的证据。淋巴管生成活性高的患者是淋巴管生成相关治疗的候选者。
