子宫内膜癌中STAT3蛋白的表达及临床意义

目的:探讨STAT3基因蛋白在子宫内膜癌、子宫内膜上皮内瘤变及正常子宫内膜组织中的表达及意义,探讨其与子宫内膜癌临床病理参数间的关系.方法:运用组织芯片技术与免疫组织化学相结合的方法检测45例子宫内膜癌组织、30例癌旁子宫内膜上皮内瘤变组织及30例癌旁正常子宫内膜组织中STAT3蛋白的表达,分析其与临床病理特征之间的关系.结果:STAT3蛋白在子宫内膜癌组织中的阳性表达率为73.3％,在癌旁子宫内膜上皮内瘤变组织中的阳性率为16.7％,在癌旁正常子宫内膜组织中的阳性表达率为0％,子宫内膜癌组织中的阳性表达率高于对照组,差异有统计学意义(P＜0.001),与子宫内膜癌患者的肿瘤分化程度有关,高分化组的阳性表达率低于中-低分化组(P＜0.05),与肿瘤临床分期、患者年龄、肌层浸润及绝经情况无关(P＞0.05).结论:子宫内膜癌组织中STAT3呈高表达,STAT3的阳性表达率与肿瘤分化程度相关,高分化的子宫内膜癌组的阳性表达率明显低于中-低分化组,可能与子宫内膜癌的发生发展有关.     

胃癌,大肠癌中c—myc癌基因的扩增及临床意义

17例胃癌、22例大肠癌及癌旁组织经PCR扩增及电泳带激光扫描测定c－myc基因改变。其中，胃癌癌组织c－myc扩增29．14％，癌旁组织组织扩增30．77％；大肠癌癌组织c－myc扩增45．45％，癌旁组织为37．5％。c－myc扩增多发生在低分化癌中。提示肿瘤分化和c－myc基因扩增之间存在着一定的相关性。组织分化愈差，c－myc扩增比率愈高。因此，c－myc扩增情况可以作为判断预后又指导治疗的指标。     

Survivin基因在子宫内膜癌组织中的表达及其临床意义

目的检测子宫内膜癌组织中survivin基因的表达及其与子宫内膜癌病理学因素间的关系。方法采用RT PCR方法检测survivinmRNA在24例子宫内膜腺癌组织及11例正常子宫内膜组织中的表达。结果子宫内膜癌sur vivin表达指数明显高于正常子宫内膜,P<0.05;子宫内膜癌中survivin的表达指数与病理分期无关,P=0.5246,低分化癌的survivin表达指数明显高于高、中分化癌,P=0.001,深肌层浸润癌的sur vivin的表达指数明显高于浅肌层浸润癌,P=0.0117。结论survivin表达水平与子宫内膜癌的发生、发展密切相关,是评估子宫内膜癌恶性生物学行为的可靠指标;survivin作为凋亡抑制基因为子宫内膜癌的治疗提供了一个新靶点。     

食管鳞癌c-myc、PCNA表达的相关性研究

 应用免疫组织化学LSAB方法，检测c－myc蛋白和增殖细胞核抗原（PCNA）在食管癌及癌旁中的表达。发现食管癌中PCNA、c－myc均有不同程度的表达。癌旁上皮PCNA几乎均为阳性而c－myc仅两例重度非典型增生上皮有少数细胞弱阳性。有淋巴结转移的食管癌组PCNA阳性率和c－myc蛋白表达均显著高于无转移组。c－myc蛋白和PCNA表达之间存在较好正变关系。c－myc基因激活和PCNA在食管癌变及癌转移中协同作用。     

Survivin、ER在子宫内膜癌组织中表达的研究及相关性分析

目的 探讨Survivin、ER在子宫内膜癌组织中的表达及相关性.方法 应用免疫组化SP法,检测60例子宫内膜癌、34例癌旁组织和20例正常子宫内膜标本中Survivin、ER蛋白的表达情况.结果 ①Survivin蛋白在子宫内膜癌组织的阳性表达率为65.0%,显著高于正常内膜组织(5.0%)及癌旁组织(8.8%)(P＜0.001).②ER在正常子宫内膜及癌旁组织中的阳性表达率分别为100.0%、94.1%,均高于其在子宫内膜癌组织中的表达(50.0%)(P＜0.001).③Survivin随着晚临床分期、组织低分化、深肌层浸润及发生淋巴结转移表达增高(P＜0.05),ER表达与组织学分级、肌层浸润程度有关(P＜0.05).④Survivin与ER在子宫内膜癌组织中的表达呈负相关(γ=﹣0.314,P=0.014).结论 Survivin在子宫内膜癌的发生、发展过程中发挥着重要作用,ER随细胞恶变发生改变.对Survivin、ER表达水平的联合检测在子宫内膜癌的诊断、治疗及判断预后方面有一定的指导意义.     

bax基因在子宫内膜癌中的表达及意义

目的研究bax基因在子宫内膜癌发生发展中的作用。方法采用RT-PCR方法检测8例正常增殖期子宫内膜、6例子宫内膜单纯及复合增生、6例子宫内膜不典型增生及42例子宫内膜癌组织中bax基因mRNA的表达。结果以8例正常增殖期子宫内膜为表达参照,在1例子宫内膜复合增生、2例子宫内膜非典型增生和27例（64.3%）子宫内膜癌中,bax基因mRNA过表达,其余为中度表达。在子宫内膜癌中,随着临床分期及组织学分级的增加、肌层侵袭的加深以及淋巴结的转移,bax基因mRNA过表达阳性率逐渐增加（除临床分期P＞0.05外,其余均P＜0.05）。结论bax基因参与子宫内膜细胞增殖与凋亡过程,与子宫内膜癌的发生发展有关,可作为评估子宫内膜癌高危因素和恶性生物学行为的重要参考指标之一。     

Fhit 在子宫内膜癌组织中的表达及临床意义

  目的 探讨脆性组氨酸三联体基因蛋白Fhit在子宫内膜癌组织中的表达及临床意义. 方法 免疫组化SP法检测12例正常子宫内膜,32例子宫内膜增殖症,42例子宫内膜癌组织中Fhit蛋白表达情况. 结果 Fhit蛋白在子宫内膜癌组织中存在表达下降现象,其表达下降率为40.5%,在正常子宫内膜及子宫内膜增殖症中Fhit蛋白均为阳性表达,癌组织与其相比,差异具有统计学意义(P<0.05).癌组织中,Fhit蛋白表达下降与组织学病理分级、手术临床分期、肌层浸润和淋巴结转移有关(P<0.05),而与患者的年龄、月经状况、组织学类型等无关(P＞0.05).结论 Fhit蛋白表达下降与子宫内膜癌的发生、发展关系密切,可作为判断子宫内膜癌恶性程度的指标.     

正常子宫内膜、子宫内膜增殖症及子宫内膜癌ras、HER-2/neu癌基因表达的研究

为研究ｒａｓ、ＨＥＲ－２／ｎｅｕ癌基因的表达与子宫内膜癌发生、发展的关系，本文用免疫组化ＡＢＣ法检测了２３例正常子宫内膜、４４例子宫内膜增殖症及１０３例子宫内膜癌组织中ｒａｓ、ＨＥＲ－２／ｎｅｕ癌基因的表达情况。结果表明：在子宫内膜非典型增生中即存在ｒａｓ基因的过度表达，过度表达率为２０％，子宫内膜癌ｒａｓ的过度表达率为１８．４％，且ｒａｓ的过度表达与子宫内膜癌的病理分级、分期及患者的生存率无关，说明ｒａｓ癌基因的异常表达可能与癌形成的早期有关。子宫内膜癌中ＨＥＲ－２／ｎｅｕ的过度表达率为２７．２％，ＨＥＲ－２／ｎｅｕ的过度表达与子宫内膜癌的分期无关，与分级及患者的预后有关，存在ＨＥＲ－２／ｎｅｕ过度表达者的生存率低于无过度表达者，前者的５年生存率为５４．８％，后者为７９．６％，结果提示ＨＥＲ－２／ｎｅｕ的过度表达是判断子宫内膜癌预后的生物学指标。     

子宫内膜癌多药耐药基因（MDRI）的表达及其意义

目的 探讨子宫内膜癌多药耐药基因（ＭＲＤＩ）的表达及其意义。方法 利用逆转 录聚合酶链反应（ＲＴ－ＰＣＲ），对３７例初治子宫内膜癌、１０例正常子宫内膜及１０例正常子宫肌层组织ＭＤＲＩ基因的表达进行检测，同时用ＭＴＴ法对宫内膜癌进行肿瘤本外药敏试验。结果 ３７例子宫内膜癌和１０例正常子宫内膜组织ＭＤＲ１表达均为阳性，ＭＴＴ药敏试验表达绝大多数子宫内膜癌对化疗药物具有交叉耐药性。结论子宫内膜癌对化疗的     

子宫内膜癌多药耐药基因(MDRI)的表达及其意义

目的探讨子宫内膜癌多药耐药基因（ＭＤＲ１）的表达及其意义。方法利用逆转录聚合酶链反应（ＲＴ－ＰＣＲ），对３７例初治子宫内膜癌、１０例正常子宫内膜及１０例正常子宫肌层组织ＭＤＲ１基因的表达进行检测，同时用ＭＴＴ法对宫内膜癌进行肿瘤细胞体外药敏试验。结果３７例子宫内膜癌和１０例正常子宫内膜组织ＭＤＲ１表达均为阳性，ＭＴＴ药敏试验表明绝大多数子宫内膜癌对化疗药物具有交叉耐药性。结论子宫内膜癌对化疗的耐药可能是一种固有性ＭＤＲ，这可能与ＭＤＲ１基因的表达有关。     

c—myc和p16在子宫内膜癌中的表达及临床意义

目的 研究癌基因c-myc和抑癌基因p16在子宫内膜癌中的表达及临床意义。方法采用免疫组化(S-P)法检测10例增生子宫内膜、22例子宫内膜不典型增生、42例子宫内膜癌中c-myc和p16基因表达,并分析其与子宫内膜癌发生、发展及预后的关系。结果 (1)c-myc在子宫内膜癌中的阳性率为26.19％(11/42),显著高于增生子宫内膜(均显阴性)及子宫内膜不典型增生(4.55％;P<0.05,P<0.05);c-myc在子宫内膜癌中的表达与组织学分级、临床分期显著相关(P<0.01,P<0.05),但与肌层浸润深度及淋巴结转移无关(P>0.05,P>0.05)。(2)p16在子宫内膜癌的阳性率为69.05％(29/42),显著低于增生子宫内膜(100％,10/10)及子宫内膜不典型增生(90.91％,;P<0.05,P<0.05);p16的表达与组织学分级、肌层浸润深度、临床分期及淋巴结转移显著相关(P<0.05,P<0.05,P<0.01,P<0.05)。结论 癌基因c-myc和抑癌基因p16可能在子宫内膜癌的发生、发展及转归中起着重要作用。     

Analysis of oncogene alterations in human endometrial carcinoma: prevalence of ras mutations

The molecular genetics of human endometrial carcinoma have yet to be defined to any significant extent. Cell lines from 11 endometrial carcinomas were examined for alterations in proto-oncogenes that might predictably be present, based on existing data from the better-characterized human carcinomas of the uterine cervix, ovary, and breast. Codons 12, 13, and 61 of the Ha-ras, Ki-ras, and N-ras genes were examined for possible point mutations, and the c-erbB2/neu, c-myc, and epidermal growth factor receptor (EGFR) genes were examined for amplification or overexpression. Ras mutations were found in seven of 11 (64%) tumors, including three in codon 61 of Ha-ras (CAG----CAT) and four in codon 12 of Ki-ras (GGT----GAT in two and GGT----GTT in two). No evidence was found for amplification or overexpression of the c-erbB2 or EGFR genes in any tumor. One tumor contained amplified c-myc sequences and exhibited relative overexpression of c-myc. These data suggest that the amplification or overexpression of several proto-oncogenes frequently observed in other human gynecologic and breast tumors are not prevalent in endometrial carcinoma and that ras gene mutations are relatively common in this tumor type.     

Immunohistochemical analysis of c-myc, c-jun and estrogen receptor in normal, hyperplastic and neoplastic endometrium

To evaluate the role of c-jun and c-myc proto-oncogenes in normal, hyperplastic and neoplastic endometrium in relation to estrogen receptor (ER) status and to investigate whether these genes can be related to other histopathological features of endometrial carcinoma, 32 endometrial carcinomas, 38 endometrial hyperplasias and 22 cyclic endometria (10 proliferative and 12 secretory) were evaluated histologically. Endometrial hyperplasia cases were classified as simple and complex hyperplasia without atypia, and atypical hyperplasia. Endometrial carcinoma cases were subtyped according to the International Society of Gynecological Pathologists. Modified FIGO system was used for both grading and staging. Immunohistochemical examination was performed using antibodies to ER-alpha, c-myc and c-jun with streptavidin-biotin-peroxidase technique. The mean percentage of ER-alpha positive cells changed cyclically during the menstrual cycle, and it was the highest (96%) and the lowest (31.6%) in proliferative and carcinomatous endometrium, respectively. There was a statistically significant difference between proliferative and secretory phases and proliferative and carcinomatous endometrium in relation to ER-alpha staining (p<0.05). There was also a statistically significant difference with respect to ERalpha reactivity between secretory phase and each hyperplastic group, as well as between the carcinoma group and each hyperplastic group (p<0.05). Although not significant, the mean percentage of c-myc expressing cells in the carcinoma group was higher (15.3%) than that of proliferative phase and hyperplastic groups. The mean percentage of c-jun positive cells in proliferative endometrium was slightly higher than in secretory endometrium, and it was the highest in atypical hyperplastic endometrium (28.3%), but there was no statistically significant difference between the groups. In carcinoma cases, a positive correlation was observed between c-jun positivity and tumor grade (p=0.027, r=0.3908), but such a correlation with c-myc was not found. A positive correlation was detected between ER-alpha and c-myc expression (p=0.038, r=0.3686). A progressive loss of ER seems to be correlated with increasing malignant transformation. C-myc expression might play a role in the development of endometrial carcinoma via ER. The association between c-jun and ER appears to be lost in endometrial carcinoma. The relationship between c-myc, c-jun and ER appears to be altered in endometrial carcinoma compared to that of menstrual endometrium.     

FREQUENT DELETION OF MTS1/p16 GENE AND CORRELATION WITH CLINICOPATHOLOGICAL PARAMETERS IN ENDOMETRIAL CARCINOMA

ＥｎｄｏｍｅｔｒｉａｌｃａｒｃｉｎｏｍａｉｓｏｎｅｏｆｔｈｅｍｏｓｔｃｏｍｍｏｎｇｙｎｅｃｏｌｏｇｉｃａｌｍａｌｉｇｎａｎｔｔｕｍｏｒｓｉｎＣｈｉｎａＴｈｅｔｕｍｏｒｉｇｅｎｅｓｉｓｏｆｅｎｄｏｍｅｔｒｉａｌｃａｒｃｉｎｏｍａｉｓｔｈｏｕｇｈｔｔ...     

Expression of c-myc gene product in gastric carcinoma

The expression of c-myc oncogene product was studied in 213 cases with gastric carcinoma by an immunoperoxidase method using a monoclonal antibody (MYC-1). Fifty (23.5%) of 213 tumors showed immunoreactivity to MYC-1. The distribution of c-myc-product-positive cells was observed mainly at the marginal area of the tumor. Excess reactivity to c-myc product occurred more frequently in invasive cancers than in localized cancers, and c-myc production expression in cancer tissue correlated well with peritoneal dissemination. Patients with c-myc-protein-positive tumor had significantly poorer prognosis than those with c-myc-protein-negative tumor in invasive gastric carcinomas, and the c-myc product status correlated well with the recurrence of cancer by peritoneal dissemination. These results suggest that the expression of c-myc gene product might be related to the proliferative activity of gastric carcinoma and serve as a new biologically relevant tumor marker for determining the prognosis.     

Joining of the c-myc gene and a line 1 family member on chromosome 8 in a human primary giant cell carcinoma of the lung

A rearranged c-myc gene found in a human primary giant cell carcinoma of the lung was analyzed. The rearrangement was found in the region about 6 kilobase pairs upstream of the c-myc gene. The breakpoint was joined to a sequence carrying a Line 1 (L1) family member located on chromosome 8. This in vivo rearrangement of the c-myc gene specific to tumor cells may represent one mechanism of activation of a protooncogene during tumorigenesis or tumor progression in human cancer.     

c—myc基因在乳腺癌,膀胱癌和肾癌组织中的扩增研究

目的研究乳腺癌、膀胱癌和肾癌组织中ｃ－ｍｙｃ基因扩增情况。方法采用聚合酶链式反应（ｐｏｌｙｍｅｒａｓｅ ｃｈａｉｎ ｒｅａｃ－ｔｉｏｎ,ＰＣＲ）,对４８例恶性肿瘤ｃ－ｍｙｃ基因扩增进行研究,通过激光密度扫描仪对琼脂糖凝胶ＥＢ染色底片进行积分光密度分析。结果正常组织无ｃ－ｍｙｃ扩增,ｃ－ｍｙｃ与ｎ－ｍｙｃ＋１－ｍｙｃ比值９５％可信区间为０．０８６９－０．６２５７,乳腺癌组织ｃ－ｍｙｃ基因扩增阳性率为     

Genetic alterations of c-myc, c-erbB-2, and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas

We have analyzed genomic DNA sequences from 125 prospectively collected single unilateral primary breast carcinoma samples for the presence of alterations of c-myc, c-erbB-1, c-erbB-2, c-Ki-ras and c-Ha-ras protooncogenes. Amplification of the c-myc gene was found in 18% of the samples, and in one sample a non-germ line c-myc related DNA fragment or rearrangement was detected. We have found a significant association (P = 0.0010) between amplified c-myc gene and inflammatory carcinoma, a particularly aggressive breast cancer. The c-erbB-2 gene was amplified in 22% of the tumor samples and a rearrangement was observed once. Alteration of the c-erbB-2 gene was significantly linked to histological grade III tumors (P = 0.005) and the absence of estrogen and progesterone receptors (P = 0.036). No amplifications were observed for c-erbB-1, c-Ki-ras, and c-Ha-ras genes. About 40% of breast carcinomas contain either amplified c-myc or c-erbB-2 protooncogenes, whereas simultaneous amplification of both was seen in only one sample, suggesting the involvement of two distinct molecular mechanisms in breast cancer. Comparison of DNA from peripheral blood and tumor samples indicated loss of one c-Ha-ras allele in 29% of patients heterozygous for this polymorphism. A significant correlation (P = 0.016) between c-Ha-ras locus (11p14) allele loss and patient survival was found. These data suggest that 11p14 allelic loss plays a role in the evolution of human breast cancer, amplification of c-erbB-2 gene is associated with increasing stage of malignancy, and alteration of the c-myc gene in inflammatory breast carcinoma may contribute to the rapid progression of this human tumor subtype.     

子宫内膜癌中MTS1／p16基因缺失的研究

目的探讨ＭＴＳ１／ｐ１６基因缺失与子宫内膜癌发生发展的关系。方法采用聚合酶链式反应（ＰＣＲ）技术,扩增３２例子宫内膜癌组织的ＭＴＳ１／ｐ１６基因。结果３２例子宫内膜癌组织中,有６例出现ＭＴＳ１／ｐ１６基因缺失,缺失率为１８．８％;癌旁组织、正常子宫内膜组织和组织分级Ｇ１的癌组织未见ＭＴＳ１／ｐ１６基因缺失。结论ＭＴＳ１／ｐ１６基因缺失可能与子宫内膜癌病程进展有关,应对其进一步研究。