Alexander-Sefre F, Singh N, Ayhan A, Thomas J M, Jacobs I J
ICRF Translational Oncology Laboratory, St. Bartholomew's and the Royal London Medical and Dental School, London EC1 M 6BQ, UK.
Gynecol Oncol. 2004 Feb;92(2):653-9. doi: 10.1016/j.ygyno.2003.11.012.
Lymphovascular Invasion (LVSI) of tumour cells is marked as an important step in the process of tumour metastases and is an important prognostic factor in Endometrial Cancer (EC). Currently, the standard method for assessing LVSI is light microscopic examination of H&E stained sections. Tumour cells within lymphovascular spaces can evade detection on H&E staining if they are present in very small numbers or surrounded by a greater number of circulating cells. Dual immunostaining for epithelial and endothelial cell markers cell markers has been shown to increase detection rate of LVSI significantly.
To investigate the clinical significance of LVSI as detected by H&E (LVSI-H&E) and immunohistochemically (LVSI-IHC) in clinically stage I endometrioid EC patients. Methods. Single representative section of 90 patients with stage I endometriod EC were immunostained in accordance with established streptavidin-biotin peroxidase method using a mouse monoclonal pancytokeratin (PCK), clone AE1/AE3 and CD31 endothelial cell marker. The H&E sections and their corresponding immunostained sections were re-examined to identify LVSI. Clinical records were available on 72 patients. The following data were collected: age, race, parity, presentation, associated medical disorders (obesity, diabetes and hypertension), use of Tamoxifen or HRT, menopausal state, recurrence and survival.
Overall, LVSI was present in 45 (50%) cases and absent in 45 (50%) cases on IHC, as compared with 17 (19%) and 73 (81%) cases, respectively, on H&E. Statistical analysis revealed significant association between LVSI-H&E and depth of myometrial invasion (P < 0.0001). The median follow-up period was 161 months (range 5-207 months). During the follow-up period, six of 14 cases with evidence of LVSI-H&E presented with recurrence as opposed to six of 58 patients with no evidence (OR = 6.26, 95%: CI = 1.3-30.6). There was a significant association between tumour recurrence rate and LVSI-H&E (P = 0.01). The 5-year recurrence-free survival was 54% for the group with H&E evidence of LVSI (95%: CI = 44-64%) compared with 89% for the group without (95%: CI = 82-97%). There was a significant difference in the recurrence-free survival between the two groups (Chi-square = 6.96, P = 0.008). In contrast, LVSI-IHC was found to be significantly associated only with high-grade tumours (P = 0.01) and survival analysis revealed no statistically significant association with recurrence or survival.
LVSI-H&E in stage I EC remains an important predictive factor of recurrent disease and reduced disease-free interval. Immunohistochemically detected LVSI is a common event, associated with tumour grade and appears to be of no statistically significant clinical value.
肿瘤细胞的淋巴管浸润（LVSI）被视为肿瘤转移过程中的重要步骤，也是子宫内膜癌（EC）的重要预后因素。目前，评估LVSI的标准方法是对苏木精-伊红（H&E）染色切片进行光学显微镜检查。如果淋巴管腔内的肿瘤细胞数量极少或被大量循环细胞包围，那么在H&E染色下可能无法检测到。上皮细胞和内皮细胞标志物的双重免疫染色已被证明可显著提高LVSI的检出率。
探讨通过H&E检测的LVSI（LVSI-H&E）和免疫组化检测的LVSI（LVSI-IHC）在临床I期子宫内膜样EC患者中的临床意义。方法：对90例I期子宫内膜样EC患者的单张代表性切片，按照既定的链霉亲和素-生物素过氧化物酶法，使用小鼠单克隆全细胞角蛋白（PCK）克隆AE1/AE3和CD31内皮细胞标志物进行免疫染色。重新检查H&E切片及其相应的免疫染色切片以确定LVSI情况。有72例患者可获取临床记录。收集了以下数据：年龄、种族、产次、临床表现、相关内科疾病（肥胖、糖尿病和高血压）、他莫昔芬或激素替代疗法的使用情况、绝经状态、复发和生存情况。
总体而言，免疫组化显示45例（50%）存在LVSI，45例（50%）不存在LVSI；相比之下，H&E检测分别为17例（19%）存在LVSI和73例（81%）不存在LVSI。统计分析显示LVSI-H&E与肌层浸润深度之间存在显著关联（P<0.0001）。中位随访期为161个月（范围5 - 207个月）。在随访期间，14例有LVSI-H&E证据的患者中有6例出现复发，而58例无证据的患者中有6例复发（OR = 6.26，95%：CI = 1.3 - 30.6）。肿瘤复发率与LVSI-H&E之间存在显著关联（P = 0.01）。有H&E证据显示存在LVSI的组5年无复发生存率为54%（95%：CI = 44 - 64%），而无LVSI的组为89%（95%：CI = 82 - 97%）。两组间无复发生存率存在显著差异（卡方 = 6.96，P = 0.008）。相比之下，发现LVSI-IHC仅与高级别肿瘤显著相关（P = 0.01），生存分析显示与复发或生存无统计学显著关联。
I期EC中的LVSI-H&E仍然是疾病复发和无病间期缩短的重要预测因素。免疫组化检测到的LVSI很常见，与肿瘤分级相关，似乎无统计学显著的临床价值。
