背景与目的:淋巴管生成在肿瘤经淋巴途径转移中所起的作用已成为近几年里新的研究热点,但目前的研究结果仍存在很多争议。本研究拟检测乳腺癌患者新辅助化疗前后的淋巴管密度(lymphatic vessel density,LVD)并与乳腺良性病变进行比较,以进一步明确淋巴管生成的意义及其在化疗过程中的变化。方法:45例原发性乳腺癌患者给予3个周期新辅助化疗并手术,免疫组化法标记肿瘤及26例纤维腺瘤标本中特异性淋巴管内皮标志物Podoplanin并计数LVD。结果:乳腺癌瘤周、瘤内的淋巴管阳性率分别为70.9%、19.8%。化疗前瘤周平均LVD为9.6,纤维腺瘤瘤周平均LVD为5.4,两者间差异有显著性(P=0.012)。化疗后瘤周平均LVD为3.3,与化疗前相比显著降低(P〈0.001),化疗前、后瘤内平均LVD分别为1.9、0.9(P=0.055)。淋巴结转移阳性和阴性组的平均瘤周LVD分别为11.8、7.0(P=0.048)。化疗后客观缓解组化疗前后平均瘤周LVD值分别为9.8、2.0(P〈0.001)。结论:与良性病变相比,乳腺癌瘤周LVD显著增高;有瘤内淋巴管存在;瘤周LVD与HER-2、腋淋巴结转移状态相关;化疗后瘤周LVD明显降低,而瘤内LVD无显著变化;化疗后瘤周LVD的降低程度与化疗疗效相关。
Background and purpose: The impact of lymphangiogenesis on cancer metastasis through lymphatics is controversial. The purpose of this study is to document the effect of neoadjuvant chemotherapy on the lymphatic vessel density (LVD) in breast cancer or breast fibroadenoma. Methods: Forty-five patients with primary breast cancer were treated with 3 cycles of neoadjuvant chemotherapy prior to surgery; and 26 cases of fibroadenoma were treated with surgery alone. LVD levels were measured by immunostaining of the lymphatic endothelial specific marker podoplanin of the tumor tissues. Results: Podoplanin-stained peri- or intra-tumoral lymphatics were identified in 70.9% and 19.8% in all patients, respectively. Peritumoral LVD of breast cancer before chemotherapy was significantly higher than that of fibroadenoma measured at 5.4 (P = 0. 012). The pre-chemotherapy peritumoral LVD of cases with or without involved axillary lymph nodes were 11.8 and 7.0, respectively ( P = 0. 048). The mean peritumoral LVD before versus after neoadjuvant chemotherapy were 9.56 versus 3.3 for the entire group of patients with invasive breast cancer ( P 〈 0. 001 ), and 9.87 versus 2.0 for patients achieved an objective response to chemotherapy (P 〈0.001). The mean intratumoral LVD in the primary breast cancer tissue before and after chemotherapy were 1.9 and 0.9, respectively (P =0.055). Condusions: Lymphatic vessel density in peripheral stromata of breast cancer tissue is significantly higher than in breast fribroadenoma, and the peritumoral LVD is positively associated with axillary lymph nodal metastasis. The peritumoral LVD demonstrated a significant reduction after neoadjuvant chemotherapy, with the amount of reduction proportional to the response to chemotherapy. The effect of chemotherapy on intratumoral LVD was insignificant.