子宫内膜癌淋巴结转移的风险评估及淋巴管生成的相关研究

发布时间：2018-06-13 01:02

本文选题：低危子宫内膜癌 + 淋巴结转移　；参考：《天津医科大学》2017年博士论文

【摘要】：目的:(1)研究低危子宫内膜癌(endometrial carcinoma,EC)淋巴切除对预后的影响,结合肿瘤直径、雌孕激素受体等临床病理因素进行低危EC淋巴结转移的风险评估。(2)研究淋巴管内皮透明质酸受体-1(lymphatic vessel endothelial hyaluronan receptor-1,LYVE-1)、同源异形盒基因转录因子-1(prospero-related homeobox-1,Prox-1)在子宫内膜癌灶内、癌旁组织中的表达,分析其与淋巴转移的关系。材料与方法:(1)回顾性分析486例术后病理为子宫内膜样腺癌的临床病理资料,分为淋巴结切除组366例,未切除淋巴结组120例。依据欧洲医学肿瘤学学会(European Society of Medical Oncology,ESMO)标准,将淋巴结切除组分为低危、中危和高危组,比较不同风险组淋巴结转移率、生存预后;计算不同风险组肿瘤直径、雌孕激素受体与淋巴结转移的临界值;评估术前、术中诊断与术后病理的一致性;分析不同风险组淋巴结切除数目、淋巴结切除组与未切除淋巴结组生存预后情况。(2)选取EC标本57例,正常内膜标本30例。留取新鲜内膜癌组织及癌旁组织15例。采用免疫组化、蛋白质免疫印迹(Western blot)、实时荧光定量PCR(reverse transcription PCR,RT-PCR)检测LYVE-1、Prox-1在内膜癌组织及癌旁组织中的表达及蛋白水平,分析与临床病理因素的关系。结果:(1)低危组淋巴结转移率显著低于中危、高危组,复发率亦低于中危、高危组。(2)淋巴结受累与肿瘤直径是否大于2cm无相关,中高危组肿瘤直径与淋巴结转移临界值为47.5mm;总体ER、PR阳性率与淋巴转移的临界值分别为55.0%、32.5%。(3)淋巴结切除组术前刮宫与术后病理的符合率57.3%,术前磁共振诊断侵肌情况与术后病理符合率80.0%;未切除淋巴结组术中冰冻与术后病理组织学分级符合率70%;侵肌符合率97.8%。(4)不同风险组切除淋巴结数目与生存预后比较无统计学差异。(5)淋巴结切除组与未切除淋巴结组复发率、死亡率及5年累计生存率均无统计学差异。(6)子宫内膜癌灶内LYVE-1、Prox-1的阳性表达率低于正常子宫内膜;两者在子宫内膜癌旁组织的阳性表达均显著高于癌灶内和正常内膜。(7)子宫内膜癌灶内LYVE-1阳性表达与所有病理因素均无关;Ⅰ型内膜癌不同组织分级与Prox-1在子宫内膜癌灶内的阳性表达具有统计学差异。(8)LVSI情况与LYVE-1在子宫内膜癌旁组织表达的阳性率差异具有统计学意义;LVSI阳性、晚期患者Prox-1在子宫内膜癌旁组织表达的阳性率升高,差异具有统计学意义。(9)淋巴结转移者癌旁组织中LYVE-1、Prox-1蛋白水平均上调,高于无淋巴结转移者。结论:(1)早期低危EC淋巴结转移风险小,不推荐常规的腹膜后淋巴结切除;淋巴结受累与肿瘤直径是否大于2cm无相关性;术前、术中正确评估低危因素至关重要;切除淋巴结的数目与患者预后无相关;未行淋巴结切除的早期低危患者如术后出现高危因素或手术分期提高,可补充辅助性治疗,预后依然乐观。(2)子宫内膜癌旁组织中淋巴管生成与淋巴结转移相关,Prox-1可能与子宫内膜癌疾病进展有关。
[Abstract]:Objective: (1) to study the prognosis of low risk endometrial carcinoma (endometrial carcinoma, EC), and to evaluate the risk of low risk EC lymph node metastasis combined with the tumor diameter, estrogen receptor and other clinicopathological factors. (2) study the lymphatic endothelium hyaluronic acid receptor -1 (lymphatic vessel endothelial hyaluronan receptor-1, LYVE-1) The expression of -1 (prospero-related homeobox-1, Prox-1) in endometrial carcinoma and the relationship with lymphatic metastasis. Materials and methods: (1) retrospective analysis of the clinicopathological data of 486 cases of postoperative pathology of endometrioid adenocarcinoma, divided into 366 cases of lymph node resection group and unresectable lymphadenectomy According to the European Institute of Medical Oncology (European Society of Medical Oncology, ESMO), the lymph node resection group was divided into low risk, middle risk and high risk groups. The lymph node metastasis rate and survival prognosis of different risk groups were compared, and the tumor diameter of different risk groups, the critical value of estrogen receptor and lymph node metastasis were calculated, and the evaluation of the operation was evaluated. The preoperative diagnosis was consistent with the postoperative pathology; the number of lymph nodes excised in different risk groups and the survival prognosis of lymph node excision group and unresected lymph node group were analyzed. (2) 57 cases of EC specimens and 30 normal endometrium specimens were selected, and 15 cases of fresh intima cancer tissue and para cancerous tissue were retained. Immunohistochemistry and protein immunoblotting (Western blot) were used. Real-time fluorescent quantitative PCR (reverse transcription PCR, RT-PCR) was used to detect the expression and protein level of LYVE-1, Prox-1 in endometrial tissue and para cancer tissues and the relationship between the clinicopathological factors. Results: (1) the lymph node metastasis rate in the low risk group was significantly lower than that in the middle risk group, and the high risk group was also lower than the middle risk, high risk group. (2) lymph node involvement and swelling. Whether the diameter of the tumor was more than 2cm was not related, the critical value of the tumor diameter and lymph node metastasis in the middle and high risk groups was 47.5mm; the total ER, the PR positive rate and the critical value of lymph metastasis were 55%. The coincidence rate of the curettage between the curettage before and after the operation in 32.5%. (3) lymph node excision group was 57.3%, and the coincidence rate of the invasion of the muscle before operation and the postoperative pathologic coincidence rate was 80%. The coincidence rate of freezing and postoperative histopathology in lymph node group was 70%, and the number of excised lymph nodes in different risk groups was no significant difference with the survival prognosis. (5) there was no statistical difference between the lymph node resection group and the unresected lymph node group recurrence rate, the mortality rate and the cumulative survival rate of 5 years. (6) endometrial cancer lesion (6) The positive expression rate of internal LYVE-1 and Prox-1 was lower than that of normal endometrium. The positive expression of both in endometrial carcinoma tissues was significantly higher than that in the carcinoma and normal endometrium. (7) the positive expression of LYVE-1 in endometrial carcinoma was not related to all pathological factors; the positive forms of different groups of endometrial carcinoma and Prox-1 in endometrial carcinoma were positive. There were statistical differences. (8) the positive rate of the expression of LVSI and LYVE-1 in endometrial carcinoma was statistically significant. LVSI positive, the positive rate of Prox-1 in the adjacent tissues of endometrial carcinoma in advanced patients was higher, and the difference was statistically significant. (9) the level of LYVE-1 and Prox-1 protein in the para cancerous tissues of the lymph node metastases were up to be up. Conclusions: (1): (1) early low risk lymph node metastasis is less risky and does not recommend conventional retroperitoneal lymph node excision; lymph node involvement is not associated with tumor diameter greater than 2cm; preoperative assessment of low risk factors is essential in the operation; there is no correlation between the number of lymph nodes and the prognosis of the patients; the removal of lymph nodes is not associated with the resection of lymph nodes. Early low risk patients, such as high risk factors or surgical stage improvement after operation, can supplement adjuvant therapy, and the prognosis is still optimistic. (2) lymphangiogenesis in the para tissue of endometrium is associated with lymph node metastasis, and Prox-1 may be associated with the progression of endometrial cancer.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R737.33

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