乳腺良恶性肿瘤新生血管超微结构及血管生成相关分子的表达

Ultrastructures of newly microvessels and expression of angiogenesis-related molecules in benign and malignant breast tumors

目的探讨乳腺良恶性不同肿瘤在新生血管超微结构及其血管生成相关分子表达方面的差异性。方法应用透射电镜观察乳腺良恶性肿瘤新生血管超微结构改变,免疫组化技术检测CD34、VEGF及其受体Flk-1/KDR在两组肿瘤中的表达特性。结果恶性组新生血管内皮细胞紧密连接开放,基膜不连续,缺乏平滑肌成分。内皮细胞胞体大,细胞核大,畸形,核仁增大、边集,核质比例增大,胞质内吞饮泡多。较多的单个内皮细胞呈裂隙状,血管腔闭塞或明显狭窄。恶性组MVD高于良性组(P<0.05),微血管丰富区位于癌巢边缘。VEGF在乳腺癌性上皮细胞及癌周血管内皮细胞呈强阳性表达,Flk-1/KDR在乳腺恶性肿瘤血管内皮细胞呈强阳性表达,VEGF及Flk-1/KDR尤其在癌灶边缘呈强阳性表达,良性组几乎不表达(P<0.05)。结论乳腺癌新生血管内皮细胞在超微结构及分子表达上具有异质性,VEGF或受体Flk-1/KDR可能是乳腺癌早期诊断及治疗的分子靶标,癌灶边缘可能是下一步进行乳腺癌分子影像观察的重点靶区。

Purpose To compare the differences in histological morphology, ultrastructures of newly microvessels and angiogenesis related molecules between benign and malignant tumor. Methods 30 cases of malignant breast tumor had 33 foci, and their histological types were as follows： infiltrating duetal carcinoma, 23 loci; infiltrating lobular carcinoma, 7 foci; intraductal carcinoma in situ, 3 loci. 30 benign breast tumors had 34 foci that were all breast fibrous adenoma. All patients were accepted histological examination. The samples of breast cancers （6 cases） , breast fibroadenoma （6 cases） and normal breast tissues （6 cases） were analyzed routinely with transmission electron microscopy. The expression of CD34, VEGF, Flk-1/KDR in both two groups were measured with immunohisto-chemical technique. Results The newborn blood vessels of breast tumor were composed of monolayer endothelial cells, and the gap between endothelial cells became wide. The basement membrane did not have continuously obvious interstitial edema. The shapes of endothelial cells were abnormal, the cell body became bigger and cytoplasm became richer and abnormal cell nucleus appeared and pinoeytotic vesicle increased. The distribution of CD34 in breast carcinoma was heterogeneous. The micro-vessels densely distributed and diffused around the margin of cancer nest. The MVD of malignant group （34.48 ± 8.34） was significantly higher than that of benign group （ 18.65 ±4. 69）. The high VEGF expression distributed diffusely or focally at the margin of cancer nest and necrotic tissue. The VEGF expression between malignant and benign group had significant difference. Flk-1/KDR expressed diffusely or focally in breast carcinoma, especially high at the margin of cancer nest and necrotic tissue. The Flk-1/KDR expression between malignant and benign group had significant difference. Conclusions The uhrastructures of newly microvessel in breast tumors are different from that of normal vascular endothelium. VEGF may play a critical role in the angiogenie process of breast tumor. The results indicate that the molecular imaging that targeted to VEGF and Flk-1/KDR may provide an new idea to explore the early diagnosis of breast carcinoma, while the margin of malignant tumor will be the target region in the molecular imaging.