伴浸润性微乳头状分化结直肠腺癌的临床病理和免疫组化特征及预后分析

发布时间：2018-05-24 14:08

本文选题：浸润性微乳头状癌 + 结直肠腺癌　；参考：《浙江大学》2017年硕士论文

【摘要】：背景:浸润性微乳头状癌被认为是具有明显侵袭性行为的罕见肿瘤。然而,胃肠道腺癌中伴浸润性微乳头状分化腺癌的病理学特征的研究报道则较为少见,特别是在结直肠腺癌中。这种罕见的组织学类型经常侵袭淋巴血管,显示侵袭性的生物学行为,导致预后不良。最近的研究显示类似于乳腺的浸润性微乳头状癌已经被报道发生在各种器官,包括膀胱、输尿管、肺和腮腺。还有报道显示在结直肠腺癌中同样发现浸润性微乳头状分化。以往对结直肠癌中伴浸润性微乳头状分化的腺癌的认识尚受到限制,对该类型腺癌的临床意义尚不十分清楚。以前的原发性浸润性微乳头状分化胃肠癌的研究显示E-钙粘蛋白(E-Cadherin)表达下调,和存在于其他器官一样,意味着伴浸润性微乳头状分化在结直肠腺癌中的存在是一个不良的预后因素。材料和方法:1.回顾性分析2007年1月至2009年12月期间浙江大学附属第二医院治疗的134例行手术治疗的结直肠癌病例,其中存在伴浸润性微乳头状分化的结直肠腺癌组53例,与同一时期行手术治疗的无微乳头状分化的对照组腺癌81例,对比分析两组腺癌的临床病理学特征。2.通过免疫组化方法研究分析EMA、CD10、E-Cadherin在伴浸润性微乳头状分化结直肠腺癌和无微乳头状分化普通结直肠腺癌中的表达差异。3.采用SPSS16软件进行统计学分析。结果:1.实验组53例(39.5%)组织学显示伴浸润性微乳头状分化;对照组58例(43.3%)为无微乳头分化普通中-高分化腺癌及23例(17.2%)为无微乳头分化普通低分化腺癌。中位年龄为伴浸润性微乳头状分化的结直肠腺癌组和对照组分别为62.1±11.2岁和60.4±12.1岁(P=0.37)。在性别分布,伴浸润性微乳头状分化的结直肠腺癌组中男性32(60.4%)例;对照组中男性49(60.5%)例(P=0.565)。在肿瘤部位,伴浸润性微乳头状分化组在结肠有36(67.9%)例,直肠有17(32.1%)例;对照组中结肠48(59.3%)例,直肠33(40.7%)例(P=0.203),差异均无显著统计学意义。2.组织病理学表现相比。伴浸润性微乳头状分化的结直肠腺癌组和对照组在肿瘤大体类型上,伴浸润性微乳头状分化的结直肠腺癌组多见为溃疡型,占58.5%;而对照组多见为隆起型,占70.4%,差异具有明显统计学意义(P0.001)。在原发肿瘤的大小上发现,肿瘤的长径在伴浸润性微乳头分化的结直肠腺癌组明显小于对照组(P0.001)。在肿瘤浸润的深度,伴浸润性微乳头状分化的结直肠腺癌组浸润至粘膜下层0(0%)例,肌层及浆膜下层12(22.6%)例,穿透浆膜层41(77.4%)例;对照组浸润至粘膜下层4(4.9%)例,肌层及浆膜下层33(40.7%)例,穿透浆膜层44(54.3%)例(P=0.015)。3.本研究发现,在肿瘤组织的侵袭程度上,淋巴侵犯、血管侵犯和神经侵犯在两组之间均有明显统计学差异,伴浸润性微乳头状分化的结直肠腺癌组的血管侵犯程度明显高于对照组(13.2%和2.5%);神经侵犯程度也明显高于对照组(18.9%和3.7%);伴浸润性微乳头状分化的结直肠腺癌组中有66%存在淋巴结转移,高于对照组的49.4%。其中淋巴结阳性数量上两组之间差异具有显著统计学差异,伴浸润性微乳头状分化的结直肠腺癌组的3.8±1.7个和对照组的2.4±1.1个(P0.001)。此外,手术中发现伴浸润性微乳头状分化的结直肠腺癌组有12(22.6%)例发现有远处转移,而对照组为4(4.9%)例有远处转移(P0.001)。但是在淋巴结检出数目上差异无统计学意义,伴浸润性微乳头状分化的结直肠腺癌组为13.5±4.9个,对照组为14.4±5.6个(P=0.897)。术后肿瘤病理分级,伴浸润性微乳头状分化的结直肠腺癌组15(28.3%)例为Ⅰ～Ⅱ期,38(71.7%)例为Ⅲ-Ⅳ期;而对照组中分别为 38(46.9%)例和 43(53.1%)例(P=0.023)。4.在免疫组化结果中,伴浸润性微乳头状分化的结直肠腺癌组的微乳头癌细胞簇EMA抗体"内向外"阳性模式有48(90.6%)例,阴性有5(9.4%)例;与无微乳头分化的对照组相比,在各个分类之间差异均有意义(P=0.001)。伴浸润性微乳头状分化的结直肠腺癌组的微乳头癌细胞簇CD10抗体"内向外"阳性模式8(15.1%)例,阳性17(32.1%)例,阴性28(52.8%)例;与无微乳头分化的对照组相比,在各个分类之间差异均有意义(P=0.001)。E-cadherin抗体在伴浸润性微乳头状分化组癌细胞簇34(64.2%)例阳性,19(35.9%)例微乳头癌细胞簇细胞与细胞接触面弱阳性及间质侧膜阴性;在无微乳头状分化组所有病例81(100%)例均阳性,在各个分类之间差异均有意义(P0.001)。5.在生存时间上,两组具有显著统计学差异,伴浸润性微乳头状分化的结直肠腺癌组明显低于对照组(31.9±16.5月和37.8±14.7月,P=0.032)。此外,研究还发现伴浸润性微乳头状分化结直肠腺癌患者的3年无病生存率是40.5%,而同时期对照组的3年无病生存率为72.6%(P=0.02)。此外,如图3.4所示,伴浸润性微乳头状分化的结直肠腺癌的患者3年总生存率为59.3%,而对照组为80.6%(P=0.07)。6.单变量分析结果显示以下因素是患者生存的重要指标参数:浸润性微乳头状分化(P=0.001),肿瘤浸润深度(P=0.015),肿瘤类型(P0.001),血管侵犯(P=0.020),神经侵犯(P=0.004),淋巴结转移(P=0.042),手术时远处转移(P0.001),肿瘤分期(P=0.023)。为进一步评估这8个因素的意义,进行多变量分析。多因素分析与Cox比例风险模型显示是否伴有浸润性微乳头状分化(OR:4.28,95%置信区间(CI)1.493～12.320,P0.01)和淋巴结转移[OR:6.29,95%置信区间(CI):1.749～22.686,P0.01)是无病生存的独立预后因素,而肿瘤侵犯程度不是无病存活的独立预后因素。结论:1.伴浸润性微乳头状分化的结直肠腺癌与普通腺癌患者在性别、年龄、肿瘤部位上无明显差异。2.伴浸润性微乳头状分化的结直肠腺癌组患者显示为明显的血管侵犯,神经侵犯,淋巴结转移倾向,预后较普通结直肠腺癌组更差。3.CD10在部分伴浸润性微乳头状分化结直肠腺癌病例中表达形式如同EMA一样为"内向外"阳性模式。
[Abstract]:Background: invasive micropapillary carcinoma is considered to be a rare tumor with obvious invasive behavior. However, the pathological features of the invasive micropapillary differentiated adenocarcinoma in the gastrointestinal adenocarcinoma are rarely reported, especially in the colorectal adenocarcinoma. This rare histologic type often invades the lymphatic vessels and shows invasiveness. Biological behavior, resulting in poor prognosis. Recent studies have shown that invasive micropapillary carcinoma similar to the breast has been reported in various organs, including the bladder, ureter, lung, and parotid gland. Also, invasive micropapillary differentiation is also found in colorectal adenocarcinoma. The recognition of adenocarcinoma of the differentiated adenocarcinoma is still limited. The clinical significance of this type of adenocarcinoma is not yet very clear. Previous studies of primary invasive micropapillary differentiated gastric cancer showed that the expression of E- cadherin (E-Cadherin) was downregulated, as in other organs, implying invasive micropapillary differentiation in colorectal adenocarcinoma. Existence is a bad prognostic factor. Materials and methods: 1. retrospective analysis of 134 cases of colorectal cancer treated by surgical treatment in the Second Affiliated Hospital of Zhejiang University from January 2007 to December 2009, including 53 cases of colorectal adenocarcinoma with invasive micropapillary differentiation, and non micropapillae treated with surgical treatment at the same time. A comparative analysis of 81 cases of adenocarcinoma in the control group. Comparative analysis of the clinicopathological features of the two groups of adenocarcinoma.2., the differential expression of EMA, CD10, and E-Cadherin in the adenocarcinoma with invasive micropapillary differentiated colorectal adenocarcinoma and non micropapillary differentiation of common colorectal adenocarcinoma was analyzed by SPSS16 software. 1. in the experimental group, 53 cases (39.5%) showed invasive micropapillary differentiation, and 58 cases in the control group (43.3%) were common medium high differentiated adenocarcinoma with no micropapillary differentiation and 23 cases (17.2%) as common low differentiated adenocarcinoma with no micropapillary differentiation. The median age of colorectal adenocarcinoma with invasive micropapilloma and the control group were 62.1 + 11.2 and 6, respectively. 0.4 + 12.1 years (P=0.37). In the sex distribution, 32 (60.4%) in the colorectal adenocarcinoma group with invasive micropapillary differentiation, 49 (60.5%) in the control group (P=0.565). In the tumor site, there were 36 (67.9%) in the colon with invasive micropapillary differentiation, 17 (32.1%) in the colon, 48 (59.3%) in the colon and rectal 33 (P=0) cases in the control group (P=0 .203), there was no significant difference in statistical significance of the.2. histopathological findings. The colorectal adenocarcinoma with invasive micropapillary differentiation and the control group were mostly ulcerated in the colorectal adenocarcinoma group with invasive micropapillary differentiation, accounting for 58.5%, while those in the group were mostly protuberant type, accounting for 70.4%, and the difference had obvious unification. Study significance (P0.001). The size of the primary tumor was found to be significantly smaller in the colorectal adenocarcinoma group with invasive micropapillary differentiation (P0.001). The depth of the tumor infiltration, with invasive micropapillary differentiation of the colorectal adenocarcinoma group infiltrated to 0 (0%) cases of the submucosa, and 12 (22.6%) cases of the muscularis and subserous layer. The serous layer 41 (77.4%) cases; the control group infiltrated to the submucosa 4 (4.9%) cases, myometrium and subserous layer 33 (40.7%) cases, penetrating serous layer 44 (54.3%) cases (P=0.015).3. study found that in the invasion degree of tumor tissue, lymphatic invasion, vascular invasion and nerve invasion were statistically significant differences between two groups, with invasive micropapillary differentiation. The degree of vascular invasion in the colorectal adenocarcinoma group was significantly higher than that in the control group (13.2% and 2.5%), and the degree of nerve invasion was significantly higher than that of the control group (18.9% and 3.7%), and 66% of the colorectal adenocarcinoma with invasive micropapillary differentiation had lymph node metastasis, which was higher than the 49.4%. in the control group, and the difference between the two groups was significant. The statistical difference was 3.8 + 1.7 in the colorectal adenocarcinoma group with invasive micropapillary differentiation and 2.4 + 1.1 in the control group (P0.001). In addition, 12 (22.6%) cases of colorectal adenocarcinoma with invasive micropapillary differentiation were found to have distant metastasis, while 4 (4.9%) in the control group had distant metastasis (P0.001), but in lymph node examination. There was no statistically significant difference in number, 13.5 + 4.9 in the colorectal adenocarcinoma group with invasive micropapillary differentiation, 14.4 in the control group (P=0.897), and 15 (28.3%) in the colorectal adenocarcinoma group with invasive micropapillary differentiation in 15 (28.3%) and 38 (71.7%) in stage III to IV; and 38 (46.) in the control group. 9%) 9% cases and 43 (53.1%) cases (P=0.023).4. in the results of immunohistochemical staining, 48 (90.6%) and 5 (9.4%) cases of micropapillary carcinoma cell cluster EMA antibody in the colorectal adenocarcinoma group with invasive micropapillary differentiation, and 5 (9.4%) negative. Compared with the control group without micropapillary differentiation, there were significant differences between the various classifications (P=0.001). 8 (15.1%) cases of CD10 antibody "introvert" positive pattern in the colorectal adenocarcinoma group with moist micropapillary differentiation, positive 17 (32.1%) and negative 28 (52.8%). Compared with the control group without micropapillary differentiation, there were significant differences in various classifications (P=0.001).E-cadherin antibody in the invasive micropapillary differentiation group. 34 (64.2%) positive, 19 (35.9%) cases of micropapillary carcinoma cell cluster cells and cell contact surface weak positive and interstitial lateral membrane negative, all cases 81 (100%) cases in the non micropapillary differentiation group were positive, the difference between the various categories was significant (P0.001).5. in the survival time, two groups with significant statistical difference, accompanied by invasive micropapilla. The differentiated colorectal adenocarcinoma group was significantly lower than the control group (31.9 + 16.5 months and 37.8 + 14.7 months, P=0.032). In addition, the 3 year disease free survival rate of patients with invasive micropapillary differentiated colorectal adenocarcinoma was 40.5%, while the 3 year disease-free survival rate in the same period control group was 72.6% (P=0.02). In addition, as shown in Figure 3.4, accompanied by infiltrating micropapilla nipples. The total 3 year survival rate of the patients with colorectal adenocarcinoma was 59.3%, while the control group was 80.6% (P=0.07).6. univariate analysis. The following factors were important parameters for the survival of the patients: invasive micropapillary differentiation (P=0.001), tumor infiltration depth (P=0.015), tumor type (P0.001), vascular invasion (P=0.020), and nerve invasion (P=0.004). Lymph node metastasis (P=0.042), distant metastasis (P0.001), and tumor staging (P=0.023). Multivariable analysis was performed to further assess the significance of these 8 factors. Multifactor analysis and Cox proportional hazard model showed whether with invasive micropapillary differentiation (OR:4.28,95% confidence interval (CI) 1.493 to 12.320, P0.01) and lymph node metastasis [OR:6.29 95% confidence interval (CI): 1.749 to 22.686, P0.01) is an independent prognostic factor for disease free survival, and the degree of tumor invasion is not an independent prognostic factor for disease-free survival. Conclusion: there is no significant difference in gender, age, and tumor location between 1. patients with invasive micropapillary differentiation and common adenocarcinoma in.2. with invasive micropapillary differentiation. The patients with colorectal adenocarcinoma showed obvious vascular invasion, nerve invasion, lymph node metastasis, and worse prognosis than common colorectal adenocarcinoma. The expression of.3.CD10 in some cases with invasive micropapillary differentiated colorectal adenocarcinoma was as "introverted" positive pattern as EMA.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.34

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