子宮內(nèi)膜癌淋巴結(jié)轉(zhuǎn)移的風(fēng)險(xiǎn)評(píng)估及淋巴管生成的相關(guān)研究
本文選題:低危子宮內(nèi)膜癌 + 淋巴結(jié)轉(zhuǎn)移; 參考:《天津醫(yī)科大學(xué)》2017年博士論文
【摘要】:目的:(1)研究低危子宮內(nèi)膜癌(endometrial carcinoma,EC)淋巴切除對(duì)預(yù)后的影響,結(jié)合腫瘤直徑、雌孕激素受體等臨床病理因素進(jìn)行低危EC淋巴結(jié)轉(zhuǎn)移的風(fēng)險(xiǎn)評(píng)估。(2)研究淋巴管內(nèi)皮透明質(zhì)酸受體-1(lymphatic vessel endothelial hyaluronan receptor-1,LYVE-1)、同源異形盒基因轉(zhuǎn)錄因子-1(prospero-related homeobox-1,Prox-1)在子宮內(nèi)膜癌灶內(nèi)、癌旁組織中的表達(dá),分析其與淋巴轉(zhuǎn)移的關(guān)系。材料與方法:(1)回顧性分析486例術(shù)后病理為子宮內(nèi)膜樣腺癌的臨床病理資料,分為淋巴結(jié)切除組366例,未切除淋巴結(jié)組120例。依據(jù)歐洲醫(yī)學(xué)腫瘤學(xué)學(xué)會(huì)(European Society of Medical Oncology,ESMO)標(biāo)準(zhǔn),將淋巴結(jié)切除組分為低危、中危和高危組,比較不同風(fēng)險(xiǎn)組淋巴結(jié)轉(zhuǎn)移率、生存預(yù)后;計(jì)算不同風(fēng)險(xiǎn)組腫瘤直徑、雌孕激素受體與淋巴結(jié)轉(zhuǎn)移的臨界值;評(píng)估術(shù)前、術(shù)中診斷與術(shù)后病理的一致性;分析不同風(fēng)險(xiǎn)組淋巴結(jié)切除數(shù)目、淋巴結(jié)切除組與未切除淋巴結(jié)組生存預(yù)后情況。(2)選取EC標(biāo)本57例,正常內(nèi)膜標(biāo)本30例。留取新鮮內(nèi)膜癌組織及癌旁組織15例。采用免疫組化、蛋白質(zhì)免疫印跡(Western blot)、實(shí)時(shí)熒光定量PCR(reverse transcription PCR,RT-PCR)檢測(cè)LYVE-1、Prox-1在內(nèi)膜癌組織及癌旁組織中的表達(dá)及蛋白水平,分析與臨床病理因素的關(guān)系。結(jié)果:(1)低危組淋巴結(jié)轉(zhuǎn)移率顯著低于中危、高危組,復(fù)發(fā)率亦低于中危、高危組。(2)淋巴結(jié)受累與腫瘤直徑是否大于2cm無(wú)相關(guān),中高危組腫瘤直徑與淋巴結(jié)轉(zhuǎn)移臨界值為47.5mm;總體ER、PR陽(yáng)性率與淋巴轉(zhuǎn)移的臨界值分別為55.0%、32.5%。(3)淋巴結(jié)切除組術(shù)前刮宮與術(shù)后病理的符合率57.3%,術(shù)前磁共振診斷侵肌情況與術(shù)后病理符合率80.0%;未切除淋巴結(jié)組術(shù)中冰凍與術(shù)后病理組織學(xué)分級(jí)符合率70%;侵肌符合率97.8%。(4)不同風(fēng)險(xiǎn)組切除淋巴結(jié)數(shù)目與生存預(yù)后比較無(wú)統(tǒng)計(jì)學(xué)差異。(5)淋巴結(jié)切除組與未切除淋巴結(jié)組復(fù)發(fā)率、死亡率及5年累計(jì)生存率均無(wú)統(tǒng)計(jì)學(xué)差異。(6)子宮內(nèi)膜癌灶內(nèi)LYVE-1、Prox-1的陽(yáng)性表達(dá)率低于正常子宮內(nèi)膜;兩者在子宮內(nèi)膜癌旁組織的陽(yáng)性表達(dá)均顯著高于癌灶內(nèi)和正常內(nèi)膜。(7)子宮內(nèi)膜癌灶內(nèi)LYVE-1陽(yáng)性表達(dá)與所有病理因素均無(wú)關(guān);Ⅰ型內(nèi)膜癌不同組織分級(jí)與Prox-1在子宮內(nèi)膜癌灶內(nèi)的陽(yáng)性表達(dá)具有統(tǒng)計(jì)學(xué)差異。(8)LVSI情況與LYVE-1在子宮內(nèi)膜癌旁組織表達(dá)的陽(yáng)性率差異具有統(tǒng)計(jì)學(xué)意義;LVSI陽(yáng)性、晚期患者Prox-1在子宮內(nèi)膜癌旁組織表達(dá)的陽(yáng)性率升高,差異具有統(tǒng)計(jì)學(xué)意義。(9)淋巴結(jié)轉(zhuǎn)移者癌旁組織中LYVE-1、Prox-1蛋白水平均上調(diào),高于無(wú)淋巴結(jié)轉(zhuǎn)移者。結(jié)論:(1)早期低危EC淋巴結(jié)轉(zhuǎn)移風(fēng)險(xiǎn)小,不推薦常規(guī)的腹膜后淋巴結(jié)切除;淋巴結(jié)受累與腫瘤直徑是否大于2cm無(wú)相關(guān)性;術(shù)前、術(shù)中正確評(píng)估低危因素至關(guān)重要;切除淋巴結(jié)的數(shù)目與患者預(yù)后無(wú)相關(guān);未行淋巴結(jié)切除的早期低危患者如術(shù)后出現(xiàn)高危因素或手術(shù)分期提高,可補(bǔ)充輔助性治療,預(yù)后依然樂(lè)觀。(2)子宮內(nèi)膜癌旁組織中淋巴管生成與淋巴結(jié)轉(zhuǎn)移相關(guān),Prox-1可能與子宮內(nèi)膜癌疾病進(jìn)展有關(guān)。
[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.
【學(xué)位授予單位】:天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2017
【分類(lèi)號(hào)】:R737.33
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