肺伴粘液分泌的腺癌分子表型与临床病理特征和预后相关性研究
发布时间：2018-08-19 07:12
【摘要】：目的：探讨肺伴粘液分泌的腺癌临床病理特征,预后与ALK重排、KRAS和EGFR基因突变的相关性。材料和方法：1、选取2002年10月至2014年9月之间经根治性手术切除,病理诊断为肺伴粘液分泌的腺癌(简称粘液腺癌)的病例75例进行回顾性分析。按照2011年国际肺癌研究学会、美国胸科学会和欧洲呼吸学会(IASLC/ATS/ERS)公布的肺腺癌国际多学科分类方法(简称新分类)进行重新分类。总结粘液腺癌的临床病理特征,并分析临床病理各因素与预后和基因突变的关系。2、EnVision免疫组织化学方法检测TTF-1、NapsinA抗体的表达。使用Benchmark XT自动免疫组化染色仪检测ALK蛋白D5F3抗体的表达。采用扩增阻滞突变系统(ARMS法)法检测EGFR和KRAS基因突变。3、对75例粘液腺癌患者进行电话随访。4、运用SPSS(17.0)统计软件对数据进行统计分析。结果：1、共75例粘液腺癌患者,其中男性36例(48%),女性39例(52%)。按照新分类分为浸润性粘液腺癌(IMA)24例(32%),腺泡或乳头为主伴粘液分泌腺癌(A/P)21例(28%),实体为主伴粘液分泌腺癌(SA)20例(26.7%),粘液型微小浸润性腺癌(m-MIA)6例(8.0%),胶样癌4例(5.3%)2、 75例粘液腺癌中ALK蛋白总阳性检出率为33.3%(25/75),较常见于不吸烟、肿瘤位于上叶或中叶、中晚期(Ⅲ-Ⅳ期)、淋巴结转移阳性患者中,并主要存在于SA和具有特定组织结构如印戒细胞、筛状结构和微乳头状结构的病例中。KRAS突变率为22.7%(17/75),主要存在于浸润性粘液腺癌、肿瘤位于下叶和不具有印戒细胞结构的患者中。而EGFR突变少见,突变率仅为6.7%(5/75)。ALK重排阳性病例中检测出2例KRAS突变,未检测到EGFR突变。仅有1例检测到KRAS与EGFR联合突变。3、免疫组化抗体TTF-1、NapsinA在SA中表达阳性率明显高于其他亚型,而在IMA中表达明显低于其他亚型。但二者表达与粘液腺癌的预后无明显相关性。4、粘液腺癌1年、3年、5年无进展生存率分别为85%、64%、38%,总生存率分别为90%、67%、50%。较大肿瘤、晚期分期、淋巴结转移阳性因素与预后差相关。KRAS突变是术后进展的阳性因素。不同亚型粘液腺癌预后差异有统计学意义,其中预后最好者为m-MIA,其他依次为IMA、SA、A/P.结论：1、不同组织亚型的粘液腺癌具有不同的分子表型,SA和具有印戒细胞、筛状结构和微乳头状结构的粘液腺癌患者ALK重排阳性率较高；IMA和不具有印戒细胞结构的患者KRAS突变率高。该结果为筛选粘液腺癌患者靶向治疗提供了形态学和分子学依据。2、不同组织学亚型的粘液腺癌临床病理特征、免疫标志物表达、基因突变率的差别具有统计学意义,该结果为粘液腺癌组织亚型的鉴别诊断提供依据.3、粘液腺癌的预后与肿瘤大小、分期和淋巴结转移相关,较大肿瘤、晚期分期、淋巴结转移阳性患者预后差。KRAS突变是术后进展的阳性因素。不同亚型粘液腺癌预后差异有统计学意义,其中预后最好者为m-MIA,其他依次为IMA、SA、A/P。4、新分类未将A/P单独列为一种亚型,A/P单独列出具有重要临床意义。
[Abstract]:Objective: To investigate the clinicopathological features and prognosis of lung adenocarcinoma with mucus secretion, and the correlation between ALK rearrangement, KRAS and EGFR gene mutation.Materials and Methods: 1. 75 cases of lung adenocarcinoma with mucus secretion (referred to as mucinous adenocarcinoma) were retrospectively analyzed. According to the International Multidisciplinary Classification of Lung Adenocarcinoma (IASLC/ATS/ERS) published by the International Society for Lung Cancer Research in 2011, the American Thoracic Society and the European Respiratory Society (IASLC/ATS/ERS), the clinical and pathological characteristics of mucinous adenocarcinoma were summarized and the relationship between clinical and pathological factors, prognosis and gene mutation was analyzed. TTF-1 and NapsinA antibodies were detected by chemical methods. The expression of ALK protein D5F3 antibodies was detected by Benchmark XT automatic immunohistochemical staining. EGFR and KRAS gene mutations were detected by amplification blocking mutation system (ARMS method). 75 patients with mucinous adenocarcinoma were followed up by telephone. 4. SPSS (17.0) statistical software was used to analyze the data. Results: 1. There were 75 cases of mucinous adenocarcinoma, 36 males (48%) and 39 females (52%). According to the new classification, there were 24 cases (32%) of invasive mucinous adenocarcinoma (IMA), 21 cases (28%) of acinar or papillary adenocarcinoma with mucinous secretion (A/P), 20 cases (26.7%) of solid adenocarcinoma with mucinous secretion (SA), 6 cases (8.0%) of mucinous minimal invasive adenocarcinoma (m-MIA). The total positive rate of ALK protein was 33.3% (25/75) in 4 cases (5.3%) of gelatinous carcinoma and 75 cases of mucinous adenocarcinoma. KR was more common in non-smoking, upper or middle lobe, middle and advanced stage (stage III-IV), lymph node metastasis, and mainly existed in SA and cases with specific histological structures such as signet ring cells, cribriform and micropapillary structures. The mutation rate of AS was 22.7% (17/75), mainly found in invasive mucinous adenocarcinoma, tumor located in the lower lobe and without signet ring cell structure. EGFR mutation was rare, and the mutation rate was only 6.7% (5/75). Two KRAS mutations were detected in ALK rearrangement positive cases, but no EGFR mutation was detected. Only one case detected KRAS and EGFR combined mutation.3, immunohistochemistry. The positive rates of antibody TTF-1 and NapsinA in SA were significantly higher than those in other subtypes, but the positive rates in IMA were significantly lower than those in other subtypes. However, there was no significant correlation between the expression of TTF-1 and NapsinA and the prognosis of mucinous adenocarcinoma. KRAS mutation is a positive factor for postoperative progression. The prognosis of different subtypes of mucinous adenocarcinoma is statistically significant. The best prognosis is m-MIA. The others are IMA, SA, A/P. Conclusion: 1. Different subtypes of mucinous adenocarcinoma have different molecular phenotypes, SA and signet ring cells, cribriform. The positive rate of ALK rearrangement was higher in mucinous adenocarcinoma patients with structure and micropapillary structure, and KRAS mutation was higher in IMA and non-signet ring cell structure patients. KRAS mutation is a positive factor for the progression of mucinous adenocarcinoma. The prognosis of mucinous adenocarcinoma is related to tumor size, stage and lymph node metastasis. The prognosis of patients with large tumor, advanced stage and positive lymph node metastasis is poor. The prognosis of liquid adenocarcinoma was significantly different. The best prognosis was m-MIA, followed by IMA, SA, A/P.4. The new classification did not classify A/P as a subtype, and A/P was listed separately as an important clinical significance.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R734.2
[Abstract]:Objective: To investigate the clinicopathological features and prognosis of lung adenocarcinoma with mucus secretion, and the correlation between ALK rearrangement, KRAS and EGFR gene mutation.Materials and Methods: 1. 75 cases of lung adenocarcinoma with mucus secretion (referred to as mucinous adenocarcinoma) were retrospectively analyzed. According to the International Multidisciplinary Classification of Lung Adenocarcinoma (IASLC/ATS/ERS) published by the International Society for Lung Cancer Research in 2011, the American Thoracic Society and the European Respiratory Society (IASLC/ATS/ERS), the clinical and pathological characteristics of mucinous adenocarcinoma were summarized and the relationship between clinical and pathological factors, prognosis and gene mutation was analyzed. TTF-1 and NapsinA antibodies were detected by chemical methods. The expression of ALK protein D5F3 antibodies was detected by Benchmark XT automatic immunohistochemical staining. EGFR and KRAS gene mutations were detected by amplification blocking mutation system (ARMS method). 75 patients with mucinous adenocarcinoma were followed up by telephone. 4. SPSS (17.0) statistical software was used to analyze the data. Results: 1. There were 75 cases of mucinous adenocarcinoma, 36 males (48%) and 39 females (52%). According to the new classification, there were 24 cases (32%) of invasive mucinous adenocarcinoma (IMA), 21 cases (28%) of acinar or papillary adenocarcinoma with mucinous secretion (A/P), 20 cases (26.7%) of solid adenocarcinoma with mucinous secretion (SA), 6 cases (8.0%) of mucinous minimal invasive adenocarcinoma (m-MIA). The total positive rate of ALK protein was 33.3% (25/75) in 4 cases (5.3%) of gelatinous carcinoma and 75 cases of mucinous adenocarcinoma. KR was more common in non-smoking, upper or middle lobe, middle and advanced stage (stage III-IV), lymph node metastasis, and mainly existed in SA and cases with specific histological structures such as signet ring cells, cribriform and micropapillary structures. The mutation rate of AS was 22.7% (17/75), mainly found in invasive mucinous adenocarcinoma, tumor located in the lower lobe and without signet ring cell structure. EGFR mutation was rare, and the mutation rate was only 6.7% (5/75). Two KRAS mutations were detected in ALK rearrangement positive cases, but no EGFR mutation was detected. Only one case detected KRAS and EGFR combined mutation.3, immunohistochemistry. The positive rates of antibody TTF-1 and NapsinA in SA were significantly higher than those in other subtypes, but the positive rates in IMA were significantly lower than those in other subtypes. However, there was no significant correlation between the expression of TTF-1 and NapsinA and the prognosis of mucinous adenocarcinoma. KRAS mutation is a positive factor for postoperative progression. The prognosis of different subtypes of mucinous adenocarcinoma is statistically significant. The best prognosis is m-MIA. The others are IMA, SA, A/P. Conclusion: 1. Different subtypes of mucinous adenocarcinoma have different molecular phenotypes, SA and signet ring cells, cribriform. The positive rate of ALK rearrangement was higher in mucinous adenocarcinoma patients with structure and micropapillary structure, and KRAS mutation was higher in IMA and non-signet ring cell structure patients. KRAS mutation is a positive factor for the progression of mucinous adenocarcinoma. The prognosis of mucinous adenocarcinoma is related to tumor size, stage and lymph node metastasis. The prognosis of patients with large tumor, advanced stage and positive lymph node metastasis is poor. The prognosis of liquid adenocarcinoma was significantly different. The best prognosis was m-MIA, followed by IMA, SA, A/P.4. The new classification did not classify A/P as a subtype, and A/P was listed separately as an important clinical significance.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R734.2
【相似文献】
相关期刊论文 前10条
1 王尚透,叶再元,吴钟玖;阑尾粘液囊肿和粘液性肿瘤[J];综合临床医学;1994年04期
2 曹仰铭;肖玉山;;卵巢粘液性肿瘤组织化学和免疫组织化学研究[J];福建医学院学报;1992年01期
3 王自能;刘咏仪;楼湘莹;杨艳东;;人卵巢粘液性肿瘤来源的再确认[J];电子显微学报;2005年06期
4 曹仰铭，，肖玉山，唐瑞文;卵巢粘液性肿瘤凝集素受体的测定[J];中华妇产科杂志;1994年09期
5 钟传庆,徐艳兰,魏宝秀,周元,曾晓南,高佑芬;卵巢粘液性肿瘤凝集素受体组织化学研究[J];临床与实验病理学杂志;1993年04期
6 廖琼,孙维纲,杨素琼,张国楠;层粘连蛋白、基质金属蛋白酶-9在卵巢粘液性肿瘤中的表达及其意义[J];实用妇产科杂志;2003年05期
7 曹仰铭;肖玉山;唐瑞文;;卵巢粘液性肿瘤病理学观察[J];福建医学院学报;1993年02期
8 江昌新,谭郁彬,李恩鸿,张大卫;卵巢粘液性肿瘤的神经内分泌分化[J];中华病理学杂志;1998年02期
9 曹光群,李涤臣,承泽龙,陶仪声,章可仪,周序陇;卵巢粘液性肿瘤组化和免疫组化研究[J];临床与实验病理学杂志;1989年04期
10 张军;;卵巢粘液性肿瘤中的肉瘤:两例报告[J];国外医学(肿瘤学分册);1980年03期
相关会议论文 前5条
1 冯晓宁;张珉;徐剑;;肝脏乳头状粘液性肿瘤一例[A];2012年浙江省外科学学术年会论文集[C];2012年
2 吕炳建;陈晓端;周彩云;张晓飞;余明华;徐恩萍;;RegⅣ在卵巢粘液性肿瘤中的表达意义[A];中华医学会病理学分会2010年学术年会日程及论文汇编[C];2010年
3 吕文玲;;112例卵巢粘液性肿瘤的组织学与组织化学变化[A];2000全国肿瘤学术大会论文集[C];2000年
4 戴林;宋秋静;回允中;;卵巢Mullerian型粘液性肿瘤[A];中华医学会病理学分会2006年学术年会论文汇编[C];2006年
5 M
本文编号：2191036
本文链接：https://www.wllwen.com/yixuelunwen/zlx/2191036.html
