胃癌c—erbB—2癌基因检测对判断肿瘤转移的意义

本文应用免疫组化方法研究１０６例胃癌石蜡标本，ｃ－ｅｒｂＢ－２染色阳性２０例（１８．９％）。ｃ－ｅｒｂＢ－２染针对性一阳性同腹膜种植、肝转移、组织类型相关。ｃ－ｅｒｂＢ－２阴性表达五年生存率高于阳性表达，但无显著差异。ｃ－ｅｒｂＢ－２对预后无显著性影响，ｃ－ｅｒｂＢ－２检测可帮助判断肿瘤转移。     

食管癌c—erbB—2原癌基因的表达及意义

目的为了探讨食管癌组织ｃ－ｅｒｂＢ－２的表达及其临床意义。方法采用ＳＰ免疫组织化学法对４１例食管癌标本进行ｃ－ｅｒｂＢ－２的检测。结果４１例食管癌中，ｃ－ｅｒｂＢ－２阳性表达率为５１．２％（２１／４１），其中高分化组ｃ－ｅｒｂＢ－２阳性率为３３．３％，中分化组为４２．１％，低分化组为７６．９％，低分化组和高分化组相比较，两组间有显著性差异（Ｐ＜０．０５）。在有淋巴结转移的食管癌中，ｃ－ｅｒｂＢ－２癌基因表达率为６５．５％（１９／２９），而无淋巴结转移者中的ｃ－ｅｒｂＢ－２癌基因阳性表达率为１６．７％（２／１２），二者相比有非常显著性差异（Ｐ＜０．０１）。１０例正常食管粘膜中ｃ－ｅｒｂＢ－２癌基因则均为阴性。结论ｃ－ｅｒｂＢ－２癌基因不仅是食管癌的一种新的标志物，而且还与食管癌的分化程度、淋巴结的转移有关，ｃ－ｅｒｂＢ－２的检测可成为食管癌诊断和判定预后有价值的指标。     

c—erbB—2,c—erbB—4原癌基因蛋白表达与乳腺癌妆生的相关关系

目的 研究ｃ－ｅｒｂＢ－２、ｃ－ｅｒｂＢ－４原癌基因过度表达与乳腺癌发生及其病理参数的相关关系。方法 对８０例乳腺癌、１６例乳腺纤维瘤、９例乳腺纤维囊性病、１７例乳腺癌转移淋巴垄石蜡切块采用免疫组化（ＬＳＡＢ法）结合计算机图像分析研究原癌基因产物ｃ－ｅｒｂＢ－２、ｃ－ｅｒｂＢ－４的表达情况。结果 Ｃ－ｅｒｂＢ－２在乳腺癌中过度表达有显著意义。ｅ－ｅｒｂＢ－２在乳腺癌转移洒巴结中的表达较原发灶中高，     

肾癌原癌基因C－erb B－2蛋白产物的表达及意义

为探讨肾癌原癌基因Ｃ－ｅｒｂＢ－２蛋白产物的表达及意义，采用免疫组化Ｓ－Ｐ（过氧化物酶－链霉卵白素）法对５５例肾癌组织中Ｃ－ｅｒｂＢ－２蛋白进行检测。显示Ｃ－ｅｒｂＢ－２蛋白呈局限性弱染色，表达率为２１．８％，与肿瘤直径相关（Ｐ＜０．０１），Ｒｏｂｓｏｎ分期Ｉ，Ⅱ期肿瘤阳性表达率明显高于Ⅲ、Ⅳ期肿瘤（Ｐ＜０．０５），随肿瘤分级增高阳性表达率呈递减趋势，颗粒细胞癌阳性表达率明显高于透明细胞癌（Ｐ＜０．０１），阳性表达组与阴性表达组预后无差异。结果提示：ＣｅｒｂＢ－２癌基因可能参与了肾癌发生的初始事件，而与晚期事件无关，强调颗粒细胞癌可能与Ｃ－ｅｒｂＢ－２癌基因关系密切。     

膀胱癌原癌基因c－erbB－2蛋白产物的表达

采用免疫组化ＰＡＰ方法对６３例膀胱癌癌基因ｃ－ｅｒｂＢ－２表达产物进行检测，２９例显示表达阳性，且阳性率在恶性度低、浅表性肿瘤中较高，Ⅰ与Ⅲ级、１＋Ⅱ与Ⅲ级、Ｔｉｓ－Ｔ１与Ｔ２～Ｔ４比较均有显著性差异（Ｐ＜０．０５），表明ｃ－ｅｒｂＢ－２蛋白表达与膀胱癌细胞分化程度、浸润程度及预后关系不大。     

p53基因和C—erbB—2基因在胃癌中的表达

为探讨ｐ５３基因和Ｃ－ｅｒｂＢ－２基因与胃癌组织分型、浸润深度、淋巴结转移、肝转移、腹膜种植及预后关系，应用免疫组化方法检测了胃癌组织中的ｐ５３基因和Ｃ－ｅｒｂＢ－２的表达情况，结果发现ｐ５３阳性染色率为２４／７２（３３．３％），Ｃ－ｅｒｂＢ－２阳性染色率２０／１０６（１８．９％）。ｐ５３阳性染色与胃癌淋巴结转移、胃癌组织分型及Ｃ－ｅｒｂＢ－２基因表达呈高度相关。Ｃ－ｅｒｂＢ－２阳性染色与胃癌腹膜种植、肝转移以及肿瘤组织分型呈正相关。ｐ５３阴性表达５年生存率（４８．９％）显著高于阳性表达（１７．６％）（Ｐ＜０．０５）。Ｃ－ｅｒｂＢ－２阴性表达５年生存率（３８．６％）高于阳性表达（２１．７％），但无统计学差异。单因素和多因素分析显示ｐ５３表达是一个独立的预后因素。单因素分析Ｃ－ｅｒｂＢ－２表达对预后无影响。     

骨肉瘤P53、c－erbB－2、c－myc的表达及与预后的关系

作者对不同临床行为骨肉瘤的抑癌基因Ｐ５３突变蛋白、ｃ－ｅｒｂＢ－２、ｃ－ｍｙｃ癌基因及增殖细胞核抗原ＰＣＮＡ进行研究。根据临床随访结果分组，高危组１０例；低危组２４例；巨大肿块组４例；转移病灶组７例。免疫组化实验ＰＣＮＡ及Ｐ５３单克隆抗体采用ＡＢＣ法染色，原位杂交实验采用地高辛试剂盒标记ｃ－ｍｙｃ、ｃ－ｅｒｂＢ－２基因探针。经统计学处理（Ｒｉｄｉｔ分析）高危组与低危组相差显著。研究结果显示，骨肉瘤Ｐ５３突变蛋白阳性表达的变化与预后有关，骨肉瘤中ｃ－ｅｒｂＢ－２、ｃ－ｍｙｃ癌基因有激活现象，阳性率较高的易转移，生存率低。骨肉瘤细胞ＰＣＮＡ均呈阳性，说明该肿瘤细胞增殖活跃，研究结果还显示骨肉瘤转移前后的组织学分型往往会改变，癌基因表达亦不同。提出可能存在第二原发灶和多中心性骨肉瘤的观点。最后作者强调术后长期持续免疫治疗和定期化疗对提高骨肉瘤生存率有重要作用。     

膀胱癌c—erbB—2癌基因蛋白表达与Ag—NORs定量计数的关系

采用免疫组化方法和胶质银染色技术对５６例膀胱移行上皮癌组织的ｃ－ｅｒｂＢ－２癌基因蛋白表达产物进行检测和对嗜银蛋白核仁组成区（Ａｇ－ＮＯＲｓ）进行定量计数，结果显示：ｃ－ｅｒｂＢ－２蛋白产物表达与膀胱癌的分化程度有关，高分级肿瘤的表达水平高于低分级肿瘤。在ｃ－ｅｒｂＢ－２表达阳性的肿瘤标本中的Ａｇ－ＮＯＲｓ计数（５．２３±０．６５）明显高于ｃ－ｅｒｂＢ－２表达阴性的标本（３．３４±０．４２）（Ｐ〈     

原癌基因C—erb B—2在肾盂输尿管癌中表达的临床意义

为了了解原癌基因Ｃｅｒｂ Ｂ－２在肾盂输尿管癌中表达的临床意义，采用免疫组化Ｓ－Ｐ法对４６例肾盂输尿管癌Ｃ－ｅｒｂ Ｂ－２蛋白表达与病理分期，细胞分级，复发与预后的关系进行研究。结果显示，肾盂输尿管癌中Ｃ－ｅｒｂ Ｂ－２蛋白表达阳性率为３４．８％，Ｔ３＋５４Ｃ－ｅｒｂ Ｂ－２表达阳性率高于Ｔ１＋Ｔ２，Ｐ〈０．０１；Ｇ３ ＣｅｒｂＢ－２表达阳性率高于Ｇ２，Ｐ〈０．０５，Ｇ１Ｃ－ｒｒｂ－Ｂ－２染色均国     

肾癌原癌基因C—erbB—2蛋白产物的表达及意义

为探讨肾癌原癌基因Ｃ－ｅｒｂＢ－２蛋白产物的表达及意义，采用免疫组化Ｓ－Ｐ（过氧化物酶－链霉卵白素）法对５５例肾癌组织中ＣｅｒｂＢ－２蛋白进行检测。显示Ｃ－ｅｒｂＢ－２蛋白呈局限性弱染色，表达率为２１．８％，与肿瘤直径相关（Ｐ〈０．０１），Ｒｏｂｓｏｎ分期Ⅰ，Ⅱ期肿瘤阳性表在明显高于Ⅲ，Ⅳ期肿瘤（Ｐ〈０．０５），随肿瘤分级增高阳性表达率呈递减趋势，颗粒细胞癌阳性表达率明显高于透明细胞癌（Ｐ〈０．０     

DNA content and c-erbB-2 oncoprotein expression in hepatic metastases from colorectal carcinoma--in relation to clinicopathologic findings and prognosis

The nuclear DNA ploidy pattern and c-erbB-2 oncoprotein expression in primary and metastatic lesions were investigated using paraffin-embedded materials from 44 cases of colorectal carcinoma with hepatic metastases and 45 cases without hepatic metastases. The frequency of aneuploidy and positive staining of c-erbB-2 in primary tumor with hepatic metastases were significantly higher compared with those without hepatic metastases (p less than 0.05). There were significant correlations between diameter of metastases and DNA ploidy pattern of the metastases and between metachronous metastases, degree of metastases, vessel involvement and DNA ploidy pattern of the primary tumor. Positive staining of c-erbB-2 was detected more frequently with the advancement of depth of tumor invasion. There was no significant correlation between DNA ploidy pattern and c-erbB-2 expression. In the survival of patients whose primary tumor and hepatic metastases were resected, it was shown that DNA ploidy pattern of metastases was the most important independent prognostic factor. Expression of c-erbB-2 in primary tumor predicted the hepatic metastases.     

Overexpression of c-erbB-2 protein and locoregional recurrence in node-positive breast cancer

The expression of c-erbB-2 protein was analysed in tumour specimens from 49 node-positive breast cancer patients with locoregional recurrence and 147 matched control patients without such events. The level of c-erbB-2 expression was quantified together with DNA content by flow cytometry. Odds ratios were calculated by matched logistic regression analysis. Nearly half of the tumours in the recurrence group (45%) showed elevated levels of c-erbB-2 compared to 25% of those in the control group. The odds ratio comparing patients with and without locoregional relapse increased significantly with increasing levels of c-erbB-2 expression. c-erbB-2 expression was a statistically significant indicator in addition to the number of lymph node metastases. Tumour size, hormone receptor status and S-phase fraction, which are known indicators of distant recurrence, were not independently associated with locoregional relapse. S-phase fraction, but not cerbB-2 overexpression, correlated with survival following locoregional recurrence.     

Cancer metastasis and recurrence from the standpoint of amplification and expression of oncogenes in human malignant tumors

We investigated the amplification and expression of oncogenes in human malignant tumors. The survival rates of patients with c-erbB, c-erbB-2, and int-2 oncogene amplification/expression were significantly lower than those of the patients without gene amplification/expression. Many distant organ metastases were observed in esophageal cancer patients with int-2 amplification, in gastric cancer patients with c-erbB-2 over-expression, and in breast cancer patients with int-2 and c-erbB-2 amplification. These results suggest that the amplification/expression of these oncogenes may serve as good markers for determining the biological malignancy of cancers.     

Genetic markers of survival and liver recurrence after resection of liver metastases from colorectal cancer

A significant number of patients with liver metastases from colorectal cancer (CRC) achieve 5-year survival after liver resection. Increased expression of genetic markers in the primary tumor are known to predict outcome after colonic resection, but the predictive value of such markers after resection of hepatic metastases is unknown. The objective of this study was to evaluate whether DNA content and multiple genetic markers, separately or expressed together, can predict patient outcome (liver recurrence and survival) after resection of hepatic metastases. We studied the paraffin-embedded liver tissue of 71 consecutive patients who had undergone a potentially curative resection of hepatic metastases from CRC. Using DNA flow cytometry and immunohistochemical staining techniques we determined the DNA content and the level of co-expression of seven tumor-associated proteins: proliferating cellular nuclear antigen (PCNA), epidermal growth factor receptor (EGFr), p53, c-erbB-2, H-ras, c-myc, and nm23. Three endpoints (liver recurrence, cancer specific, overall survival) were correlated with these tumor markers. The 5-year overall survival of the group was 31.2%. There was no correlation detected between the DNA aneuploidy and overall or cancer-specific survival. Similarly, expression of the individual tumor-associated proteins did not predict survival. Patients whose tumors co-expressed multiple markers had survivals similar to those whose tumors expressed fewer markers. However, a significant difference in hepatic recurrence was found between the p53-positive and p53-negative patients (p= 0.007), with marker-negative tumors having decreased recurrence. In conclusion, this study demonstrates that the DNA content and genetic markers c-myc, c-erbB-2, EGFr, H-ras, p53, PCNA, and nm23 do not predict survival after potentially curative resection of hepatic metastases from CRC. However, the immunoreactivity of p53 may be an important marker of local recurrence in the liver, which may be useful if re-resection of metastatic liver tumors is considered a viable management option in this disease.     

进展期结直肠癌术后联合化疗的临床观察

目的：探讨进展期结直肠癌术后静脉联合腹腔化疗的临床疗效。方法：进展期结直肠癌根治术后102例随机分成联合化疗组（观察组）与静脉化疗组（对照组）各51例，观察两组病人化疗后不良反应、术后复发和转移情况及5年内生存率，并进行分析比较。结果：观察组的胃肠道反应、骨髓抑制和急性肾功能损害的发生率明显低于对照组，腹腔和肝转移率及局部复发率低于对照组（P〈0．05），而观察组的其他远处转移率与对照组无明显差异（P〉0．05），观察组2、3、4和5年的生存率分别为98．0％、88．2％、74．4％和62．0％，明显高于对照组（86．3％、70．4％、51．8％和31．9％。结论：术后行联合化疗，降低了化疗的毒副反应，降低了术后的复发率和转移率，延长生存期，是进展期结直肠癌术后理想的化疗方式。     

Comparative clinicopathological study of resected intrahepatic cholangiocarcinoma in northeast Thailand and Japan

Northeast Thailand has a very high incidence of intrahepatic cholangiocarcinoma (ICC), which is closely linked to infestation by the liver fluke, whereas the etiology of ICC in Japan remains to be clarified. This study compared the clinicopathological features, the expression of p53 and c-erbB-2 proteins, and the proliferative activity of ICC in 19 Thai and 23 Japanese patients with ICC who were treated by hepatic resection. The average age of the Thai patients (55.8 years) was lower than that of the Japanese (61.3 years). All Thai patients presented with symptoms, whereas 8 Japanese patients were asymptomatic. There were no significant differences in preoperative liver function test values. Tumors were less likely to be located in the right lobe in the Japanese (34.8%) than in the Thai patients (63.2%). Peribiliary fibrosis and adenomatous hyperplasia in noncancerous hepatic tissues were much more frequently found in the Thai patients (P = 0.0010; P < 0.0001). No significant differences in the expression of p53 protein or c-erbB-2 protein were found between the two series of patients, but proliferative activity, evaluated on the basis of mean MIB1 labeling index, was significantly higher in the Thai patients (P < 0.001). The present study suggested a higher proliferative activity of ICC in Thai patients than in Japanese patients. Received for publication on Dec. 16, 1999; accepted on Jan. 14, 2000     

进展期胃肠道肿瘤术后联合化疗的临床疗效观察

目的:探讨进展期胃肠道肿瘤术后联合化疗的临床疗效。方法:自1994年1月至1999年12月我科对419例进展期胃肠道肿瘤根治术后的病例作了联合化疗。现就联合化疗对机体的耐受性、局部复发、腹腔种植转移、肝转移或其他远处转移和生存率的影响进行观察,并将之与同期行静脉化疗和腹腔化疗的病例进行分析比较。结果:联合化疗组病例的胃肠道反应、骨髓抑制和急性肾功能损害的发生率与腹腔化疗组相比无显著差异,但明显低于静脉化疗组(P<0.05)。静脉化疗组的肝转移和腹腔转移率(29.5%和32.8%)高于腹腔化疗组(14.2%和13.5%)和联合化疗组(12.8%和12.2%),而腹腔化疗组的其他远处转移率(18.4%)则远高于联合化疗组(11.5%)和静脉化疗组(9.8%)。联合化疗组病例的2、3、4及5年生存率分别为72.8%、65.1%、60.8%和55.2%,明显高于腹腔化疗组的59.2%、48.1%、43.8%和38.7%和静脉化疗组的58.9%、47.6%、42.9%和37.5%(P<0.05)。结论:进展期胃肠道肿瘤病人术后行联合化疗,降低了化疗的毒副反应,提高了病人的生活质量,有效地防止了病人术后的复发率和转移率,并延长了病人的生存期;是进展期胃肠道肿瘤根治术后较理想的化疗方式。     

同时性结直肠癌肝转移的临床病理特征分析

目的遴选同时性结直肠癌肝转移的危险因素，为预测和早期诊断肝转移提供参考依据。方法收集2003年1月至2006年12月间收治的367例原发性结直肠癌患者的临床病理资料，对患者的年龄、性别、血型、肿瘤家族史、是否合并肝炎肝硬化、有无合并肠梗阻、术前癌胚抗原（CEA）和CA19－9、原发肿瘤部位和大小、分化程度、肿瘤侵及深度、有无淋巴结转移、肿瘤分期等19项因素进行统计分析。结果本组发生同时性结直肠癌肝转移56例．占同期结直肠癌患者的15．3％。在发病年龄、是否有肠梗阻、是否有盆腔转移结节及肿瘤浸润深度方面，肝转移和无肝转移两组患者之间差异有统计学意义（P〈0．05）。右侧结肠癌肝右叶转移瘤者明显多于左叶，而左侧结肠癌转移瘤多分布于全叶。当术前CEA大于22．1μg／L时，患者发生肝转移的可能性增加。结论结直肠癌同时性肝转移与患者年龄、是否存在肠梗阻、盆腔有无转移及CEA水平存在密切关系。     

Prognostic significance of co-expression of c-erbB-2 oncoprotein and epidermal growth factor receptor in breast cancer patients.

The expression of c-erbB-2 oncoprotein and epidermal growth factor receptor (EGFR) was examined by immunocytochemical and radioreceptor assays in 115 patients with primary breast cancer. In 48 of 115 patients (42%), the assays were found to be positive for the expression of c-erbB-2 oncoprotein, and, in 44 of 115 (35%) patients, the assays were positive for the expression of EGFR. There was no correlation between the expression of c-erbB-2 oncoprotein and EGFR. Clinical survey demonstrated that both c-erbB-2 oncoprotein expression and EGFR expression have independent prognostic values. Furthermore, when patients were divided into three groups on the basis of the expression of both c-erbB-2 oncoprotein and EGFR, those who were found to be positive for the expression of both c-erbB-2 oncoprotein and EGFR showed a worse prognosis than other groups. These results suggest that the combination of the expression of both c-erbB-2 oncoprotein and EGFR may be important in selecting patients who have a poor prognosis.     

乳腺癌c-erbB-2与雌孕激素受体及淋巴结转移的相关性分析

目的：分析乳腺癌c-erbB-2的表达与ER、PR，以及腋窝淋巴结、肿瘤大小、病理类型的相关性。方法：收集术前未行新辅助化疗而行手术切除加腋窝清扫的乳腺癌病人346例，采用免疫组化法检测c-erbB-2、ER及PR；比较c-erbB-2表达与ER、PR、腋窝淋巴结、肿瘤大小以及病理类型之间的关系。结果：c-erbB-2阳性表达者占48．2％，腋窝淋巴结有转移者的c-erbB-2阳性表达为69．6％，而淋巴结阴性者则为34．6％（P〈0．001）。ER、PR均阳性且c-erbB-2表达也阳性者为38．1％；而ER、PR均阴性、c-erbB-2阳性者达64．6％（P〈0．001）。仅ER阳性和阴性者的c-erbB-2阳性表达分别是40．7％和69.2％（P（0．001）。仅PR阳性和阴性者的c-erbB-2阳性分别为46．4％和49．7％（P〉0．05）。〈2cm和2～5cm肿瘤的c-erbB-2阳性率分别是47．1％和48．8％（P〉0．05）。导管内癌和黏液癌的c-erbB-2表达阳性率分别达73．8％和60．0％。结论：c-erbB-2阳性表达与腋窝淋巴结的转移呈正相关，与ER呈负相关，与PR和肿瘤大小不相关。c-erbB-2是判断乳腺癌预后的良好指标。