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食管小细胞癌中P27及P73表达与其预后相关性分析

The Analysis of relations between multi-oncogene expression in Small cell esoph-ageal carcinoma and its prognosis

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【作者】 王小玲刘月平吴国祥

【Author】 Wang Xiao-Ling LiuYue-Ping Wu Guo-Xiang Department of pathology, The fourth hospital of Hebei medical university & Hebei provincial tumor hospital, Shijiazhuang, 050011, China

【机构】 河北医科大学第四医院暨河北省肿瘤医院病理科

【摘要】 目的:以食管小细胞癌作样本,鳞状细胞癌作对比。采用P27、P73联合基因检测,探讨其生物学活性及其间的差异对预后的影响,为临床治疗和判断预后提供新的理论性依据。方法:河北医科大学第四医院病理科,自1986~1996年符合小细胞癌60例,再随机选取同期鳞状细胞癌100例,每例手术切除标本均未进行术前放疗、化疗及免疫治疗。经有经验的病理医师双盲法对全部切片复诊无误后,再选取相应存档蜡块,制成厚约4μm切片3张,1张HE染色进行病理形态学观察分析,其余用于免疫组化染色,每例均用免疫组织化学S—P方法检测P27、P73基因蛋白表达。小细胞癌随访40例,鳞状细胞癌随访94例,时间为手术日至死亡日或末次随访日。结果:1.食管癌生物学特性比较;1.1小细胞癌与鳞状细胞癌生物学特性比较淋巴结转移率、瘤栓、残端阳性率分别为63.33%、35%、13.33%及21%、15%、6%。其差异均有统计学意义(P<0.01)。小细胞未分化1、3、5年生存率分别为67.5%、34.0%、10%,平均生存期限为2.6年,鳞状细胞癌1、3、5年生存率分别为78%、63%、34%,平均生存期限为4.65年,其差别均有统计学意义。(P<0.05)淋巴结转移(+)、瘤栓(+)、残端(+)与预后有相关性,而与性别、年龄、发病部位无关。1.2 I~II级与III级鳞状细胞癌生物学特性比较100例鳞状细胞癌中,I~II级64例,III 级36例,发生比例为1.78:1,瘤栓、残端阳性率分别为10. 94%、6.25%及22.22%、8.33%,其差别无显著性意义;淋巴结转移率分别为12.5%及36.11%,生存期限分别为5.275 及3.57年,其差别均有统计学意义(P<0.01)。二者生物学特性与小细胞癌比较均有非常显著性差异。从I—II至III级鳞癌及小细胞癌三者间的淋巴结转移率,依次升高;而术后生存期限则依次缩短,表明从食管癌的高分化、低分化到未分化,其间构成阶梯式程序,恶性度愈来越高,预后也愈来越差。由此证明食管癌的分化程度成为判断病人预后的重要指标之一。2.免疫组化结果:P27、P73等基因蛋白在小细胞癌表达阳性率为5%、73.33%;而在鳞状细胞癌中阳性表达率则为58.33%、51%,其差别均有统计学意义(P<0.01)。在小细胞癌中,P27阳性表达率低与预后有相关性。食管小细胞未分化及鳞状细胞癌P73基因蛋白阳性表达则与预后均有相关性。在III级及I~II级鳞状细胞癌P27、P73基因蛋白阳性表达率为30.56%、55.56%及80.56%、66.67%,其差别均有统计学意义(P<0.01)。从I—II至III级鳞状细胞癌及小细胞癌P27阳性表达率依次降低,而P73阳性表达率则依次升高,其间也构成阶梯式程序改变,且均有统计学意义,表明二者与食管癌的分化程度有显著相关性,可成为判断病人预后的重要指标之一。结论:食管小细胞癌与鳞状细胞癌相比, 组织分化极低,易发生淋巴结及血行转移,且预后极差,P27、 P73基因蛋白水平在食管小细胞癌及鳞状细胞癌中存在显著性差异。在食管小细胞癌中,两者表达与预后有关,均可作为判断预后的独立因素。证明食管癌的基因检测更具客观性。因此,应用单独或联合基因检测对于指导临床治疗,判断预后将具有十分重要的临床意义。

【Abstract】 Objective: To study the affection of multi-oncogene’ s biological behaviours and the differences among them on esophagus cancer prognosis, we detected the expression of P27 and P73 in the small cell carcinomas (ESCC) (the experimental group) and the squamous cell carcinoma (ESC) (the control group) of esophagus, which may provide a new theoretical basis for esophagus for clinical treatment and predicting prognosis. Methods: Tu- mor blocks are obtained from the Forth Hospital of Hebei Medical University from 1986-1996.We selected 60 ESCC and 100 ESC in the same period, and none of the patient had received preoperative radiotherapy, chemotherapy, immune treatment All slides were checked independently by two pathologists in blinded fashion without knowledge of the clinical and pathological information. Sections of each case are cut at 5- μm intervals of 5 slides. one is used for hematoxylin and eosin(H&E) staining, the others are used for immunhistochemical staining, and we detected the expression of P27, FHIT, PTEN and P73 in S-P immunhistochemical reaction. The follow-up ESC and ESCC are 40 and 94, the length of the follow-up period was calculated from the date of initial surgical treatment. Results: 1. The biological features between ESCC and ESC: in the ESCC and ESC ,the positive rate of the lymph node metastasis, tumor invasion and the end of the carcinoma are 63.35%,35%, 13.33% and 21%,1S%,6%, respectively. They have statistical significance. The ESCC one-year, three-year, five-year survival rates are 67.5%, 34%, 10% respectively. The median survival is 2.65 years, the ESC one-year, three-year, five-year survival rates are 8%, 63%, 34%. The median survival is 4.6 years, they have statistical significance. The lymph node metastasis, tumor invation and the end of tumor are related to the prognosis, but not related to age, sex, and position. Histologically, sixty-four are I-II graded ESC and 36 are III graded ESC, the rate is 1.78: 1.The positive rate of tumor invasion and the end of the carcinoma are 10.94%, 6.25% and 22.22%, 8.33% respectively, the positive rate of the lymph node metastasis arel2.5% and 36.11 %, the median survival period are 5.275 and 3.57 years, they have statistical significance. They both have the significance with the SCC in the biological features. From I-II to III graded SCC and ESCC, the positive rate of the lymph node metastasis are increased but the median survival period are decreased, so it indicated that from the well, moderately and poorly differentiated of esophagus carcinoma, we can see the ladder’ s sequence, the malignant extent were higher, and the prognosis were poorer. We can judge the prognosis through the differentiation. 2. Immunohistochemical staining results: the positive rate of P27 and P73 in ESCC and ESC are 5%, 44%, 33.33%, 73.33% and 58.33%, 84%, 68% and 51%. They have statistical significance. The expression of P27 and P73 are correlated with prognosis in the ESCC. In the III-graded an

  • 【会议录名称】 第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议论文集
  • 【会议名称】第四届中国肿瘤学术大会暨第五届海峡两岸肿瘤学术会议
  • 【会议时间】2006-10
  • 【会议地点】中国天津
  • 【分类号】R735.1
  • 【主办单位】中国抗癌协会、中华医学会肿瘤学分会
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