30例配对新鲜胃癌标本中p53基因突变的研究

目的：探讨胃癌标本中p53基因外显子5～8的突变情况及其与胃癌各临床特征的关系。方法：采用银染PCR—SSCP检测30例配对新鲜胃癌手术标本中p53基因外显子5～8的突变。结果：p53基因突变检出率为46．7％（14／30），p53基因外显子5—8的突变率分别为10％、16．7％、23．3％、16．7％；p53基因突变与病人年龄、性别、原发灶部位及肿瘤分化程度之间差异没有显著性意义（P〉O．05）；但是，p53基因突变与胃癌临床分期、淋巴结转移之间差异有显著性意义（P〈O．05），进展期胃癌p53基因突变高于早期胃癌，有淋巴结转移的胃癌组织中p53基因突变高于无淋巴结转移胃癌组织。结论：p53基因突变可能参与了早期胃癌一进展期胃癌的发生发展过程，并可能是胃癌发生淋巴结转移的机制之一。     

PCR-SSCP分析法检测胃癌中p27基因突变

目的　对 5例早期胃癌组织和 32例进展期胃癌及其各自的正常胃粘膜组织 ,进行p2 7抑癌基因的突变检测。方法　应用聚合酶链式反应—单链构象多态性分析 (PCR SSCP)技术进行检测。结果　在早期胃癌组织中检出突变率为 2 0 .0 %( 1/5 ) ,在进展期胃癌组织中的突变率为 2 1.9%( 7/32 )。实验结果表明 ,p2 7基因在早期胃癌与进展期胃癌中均有较高突变频率 ,两者差异无显著性 ;p2 7基因突变在胃癌中与性别、年龄以及肿瘤的位置、组织分化程度、Borrmanm分期和有无淋巴结转移无关 ;p2 7基因外显子 1是该基因突变的集中区域 ,且以第 1-90密码子区域突变率最高 ,p2 7基因外显子 2突变率最低。结论　证实了p2 7基因突变发生于早期胃癌形成阶段 ,属于胃癌发生的早期事件。     

食管癌组织中p53蛋白表达的临床意义

目的 :探讨p53蛋白表达在食管癌中的临床意义。方法 :用鼠抗人p53单克隆抗体 ,以SP免疫组化法检测p53蛋白。结果 :p53蛋白阳性表达率为 56 3% ,其表达与肿瘤大小、TNM分期、有无淋巴结转移无关 (P >0 0 5) ,与肿瘤分化程度有关 (P <0 0 1)。p53蛋白阳性组与阴性组比较 ,其术后生存率有显著差异 (P <0 0 1)。结论 :食管癌组织中p53蛋白表达与肿瘤大小、TNM分期及有无淋巴结转移无关 ,与肿瘤分化程度密切相关 ,并可用于判断预后     

食管鳞状细胞癌p16和nm23-H1基因蛋白表达及意义

目的 :探讨多肿瘤抑制基因p16蛋白和nm2 3 H1基因蛋白在人食管癌的表达及与肿瘤生物学行为的关系。方法 :应用免疫组织化学方法观察 51例食管鳞状细胞癌及其淋巴结转移癌中p16蛋白的表达 ,结合观察转移抑制基因nm 2 3 H1的表达。结果 :p16在食管鳞状细胞癌中呈低表达 ( 4 5 1% ,2 3/51) ,阳性率显著低于正常食管粘膜及癌旁组织 (P <0 0 1) ,阳性率与分化程度相关 (P <0 0 1) ,Ⅰ级66 7% ( 14/ 2 1) ,Ⅱ级 34 8% ( 8/ 2 5) ,Ⅲ级 14 3% ( 1/ 7) ;与肿瘤浸润、转移无关。nm 2 3 H1的阳性率为60 8% ( 31/ 51) ,与浸润深度呈负相关 (P <0 0 5) ,淋巴结转移癌的阳性率 ( 18 8% ,3/ 16)显著低于食管癌原发灶 (P <0 0 1)。p16与nm 2 3 H1的表达无关。结论 :p16蛋白在食管癌的低表达提示有频发性的p16基因失活 ,且与肿瘤分化有关。nm2 3 H1与食管癌的浸润 ,转移相关。p16和nm 2 3 H1的失活在食管癌的形成及发展中可能起不同的作用     

食管鳞状上皮细胞癌中P53基因突变的PCR-SSCP检测

应用PCR－SSCP银染技术检测了40例食管鳞状细胞癌p53基因第5、6、7和第8外显于的突变情况。结果显示：13例（32．5％）有p53基因突变，突变主要发生在第5和第8外显子，与癌分化程度无明显关系，但伴淋巴结癌转移病例中p53基因的突变率明显高于无转移者（P＜0．05）。本研究提示，p53基因突变存在于中、晚期食管癌中，并可能与食管鳞癌的进展与转移有关。     

肺腺癌p53基因突变与临床病理特征关系的研究

目的探讨p53基因在肺腺癌中突变的频率、位置和在肺腺癌发生发展中的作用及与其临床病理特征的关系。方法聚合酶链式反应一单链构象多态性（PCR－SSCP）检测31例肺腺癌的P53基因第5～8外显子突变。结果14例（45％）出现P53基因5～8外显子突变，其中7、8外显子突变占73％。P53基因突变男性显著高于女性（P—0．003），在肿瘤≤3cm的病例p53基因突变率显著低于肿瘤＞3cm的病例（P=0．005）。p53基因突变与吸烟史、年龄、组织学类型、分化程度、淋巴结状况、国际病理TNM分期及瘤栓无显著性差异（P＞0．05）。结论肺腺癌中P53突变率为45％，主要分布在第7、8外显子，P53基因突变参与肺腺癌癌变的始动和腺癌的进展。     

原发性食管鳞癌组织p16基因缺失的检测

目的　研究p16基因缺失与原发性食管鳞癌的相关性。方法　采用PCR方法检测 41例原发性食管鳞癌组织中p16基因的缺失情况。结果　 41例食管鳞癌组织有 6例p16基因缺失 ,缺失率为 14 .6%。低分化食管癌p16基因缺失率为 5 0 % ,高于中分化 (p =0 .0 0 0 9)和高分化食管癌 (p =0 .0 2 2 )。有淋巴结转移缺失率高于无淋巴结转移 (p =0 .0 0 3 )。结论　p16基因缺失与食管鳞癌的发生发展有相关性。     

p53蛋白在子宫颈癌组织中表达的临床意义

目的 :探讨 p5 3蛋白在子宫颈癌组织中表达的临床意义。方法 :用鼠抗人 p5 3单克隆抗体 ,以 SP免疫组化法检测 p5 3蛋白。结果 :p5 3蛋白阳性表达率为 5 6 .3 % ,其表达与肿瘤大小、TNM分期、有无淋巴结转移无关 (P>0 .0 5 ) ,与肿瘤分化程度有关 (P<0 .0 1)。 p5 3蛋白阳性与阴性组比较 ,其术后生存率差异有显著性 (P<0 .0 1)。结论 :子宫颈癌组织中 p5 3蛋白表达与肿瘤大小、TNM分期及有无淋巴结转移无关 ,与肿瘤分化程度密切相关 ,并可用于判断预后。     

p53、p16、增生细胞核抗原蛋白表达在食管癌术后放化疗选择中的意义

 【摘要】　目的　探讨食管癌p53、p16、增生细胞核抗原（PCNA）蛋白表达及其与患者病理临床特征的相关性，为食管癌患者术后放射治疗和（或）化疗的选择提供依据 。方法　选择初治食管癌病例118例，对手术切除标本，用免疫组织化学染色SP法进行p53、p16、PCNA蛋白测定。结果　118例食管癌中，p53、 p16、PCNA蛋白阳性表达分别为80 %、42 %、97 %，p53、PCNA蛋白表达与患者的性别、病变部位、肿瘤分化程度、浸润深度、有无淋巴结转移均无相关性；而p16蛋白与肿瘤浸润深度、淋巴结转移有密切相关性（P＜0.01）； p53、PCNA蛋白同时表达70 %，亦与肿瘤浸润深度、淋巴结转移密切相关（P＜0.05和P＜0.01）。结论　在食管癌组织中，突变p53与PCNA蛋白表达，二者与患者的性别、病变部位、分化程度、浸润深度、淋巴结转移均无关，不作为独立预后判断因素。食管癌p53、PCNA蛋白同时表达与肿瘤浸润深度、淋巴结转移密切相关，其与p16失活可视为危险预后因素，应行术后放射治疗和（或）化疗。     

胃癌中 p16基因表达、缺失及突变的检测

目的研究p16基因表达与胃癌发生发展、侵袭、转移的关系及p16基因外显子2缺失、突变在胃癌发生中的地位。方法运用链霉菌抗生物素蛋白-过氧化酶(S-P)免疫组织化学方法检测胃癌及癌前病变组织中p16蛋白的表达;采用聚合酶链反应(PCR)、聚合酶链反应-单链构象多态性(PCR-SSCP)分析方法检测胃癌中p16基因外显子2的缺失、突变。结果(1)p16蛋白表达阳性率①正常胃粘膜96.25％(77／80),不典型增生92.00％(45／50),胃癌47.54％(58／122),胃癌组中p16蛋白表达低于正常胃粘膜及不典型增生（P<0.05）;②粘液腺癌(10.00％,1／10)低于低分化腺癌(51.22％,21／41)、未分化癌(57.69％,15／26)和印戒细胞癌(62.50％,10／16)（P<0.05）;③30例原发癌和淋巴结转移癌配对标本中p16蛋白表达阳性率原发癌46.67％（14/30）,淋巴结转移癌16.67％(5／30),淋巴结转移癌低于原发癌(P<0.05);(2)p16基因缺失与突变分析25例胃癌中检测出缺失5例,但未发现突变。结论①p16蛋白表达缺失与胃癌的发生、组织学类型及淋巴结转移有关。②p16基因外显子2缺失可能与胃癌发生有关;而p16基因突变可能与胃癌发生无关。     

胸段食管癌的淋巴结转移规律及其对确定术后放射治疗靶区范围的价值

目的 分析胸段食管癌淋巴结转移的规律及其影响因素,探讨食管癌术后放疗的靶区范围.方法 收集763例接受根治性切除的胸段食管癌患者的临床病理资料,分析淋巴结转移规律及影响因素.结果 763例胸段食管癌患者共清除淋巴结5846枚,病理证实转移711枚,转移度为12.2%;出现淋巴结转移者297例,转移率为38.9%.胸上段癌淋巴结转移率为28.5%,明显低于胸中段癌(38.8%)和胸下段癌(43.4%).胸上段癌以锁骨上和气管旁淋巴结的转移度和转移率最高.胸中段癌的上行和下行转移均存在,上行主要转移至锁骨上、气管旁和食管旁,下行主要转移至贲门和胃左动脉旁.胸下段癌则主要向食管旁、贲门和胃左动脉旁转移,其中胃左动脉旁的转移度和转移率均显著高于胸上段癌和胸中段癌(均P<0.01).采取左胸单切口的592例患者中,胸上、中、下段癌的淋巴结转移率分别为37.0%、37.9%和41.4%,差异无统计学意义(P=0.715).多因素Logistic回归分析表明,病变长度、浸润深度、脉管瘤栓和远处转移是影响胸段食管癌淋巴结转移的主要因素(均P<0.05).结论 临床上可以根据食管癌的病变长度、浸润深度、脉管瘤栓和远处转移选择需行术后预防照射的患者,根据不同病变部位、不同手术方式及TNM分期,确定术后预防照射的靶区范围.     

Reduced expression of PTEN protein and its prognostic implications in invasive ductal carcinoma of the breast

OBJECTIVE: The PTEN tumor suppressor gene has been demonstrated to be inactivated in a variety of human tumors. In breast cancer, the PTEN gene mutation is not commonly found whereas loss of heterozygosity affecting the PTEN locus is frequently found. The aim of this study was to analyze PTEN protein expression in breast cancer and to evaluate the prognostic significance of PTEN protein expression. METHODS: Paraffin-embedded sections ofinvasive ductal carcinoma of the breast were immunohistochemically stained for PTEN protein expression in 236 breast cancers. The immunohistochemical expression of breast cancer cells was judged to be either normal or reduced compared with the PTEN protein expression of the normal mammary gland. Results: The expression of PTEN protein was found to have decreased in 67 (28%) of 236 breast cancers. The reduced expression correlated with lymph node metastasis (p = 0.0371), but not with tumor size, nuclear grade, MIB-1 counts or p53 protein expression. Univariate analysis indicated that patients with a reduced PTEN expression had a shorter disease-free survival (DFS) than those with a normal PTEN expression (p = 0.0174). Univariate analyses also determined tumor size, lymph node metastases, nuclear grade, MIB-1 counts, p53 protein as well as PTEN protein expression to be significant factors for DFS, while multivariate analysis determined lymph node metastases and the MIB-1 counts to be independent significant factors for DFS. CONCLUSIONS: The inactivation of PTEN, demonstrated by a reduced expression of PTEN protein by immunohistochemistry, was found in about one third of all breast cancers. The reduced expression of PTEN protein correlated with lymph node metastases and a worse prognosis in the patients with breast cancer.     

食管鳞状细胞癌中p16基因变异的临床意义及地域性差异

目的 进一步了解Ｐ１６基因的变异与食管癌发生发展和生物学行为的关系及地域性差异。方法 采用免疫组化和聚合酶链反应技术,对来自林县高发区和浙江省的食管癌存档组织标本中Ｐ１６蛋白的表达及其因变异进行了检测,并对食管癌组织中ｐ１６基因变异表达的临床意义及地域性差异进行了回顾性比较分析。结果 ９２例食管癌组织中,４４例存在ｐ１６蛋白表达,２２例检测到ｐ１６基因的丢失,只有５例出现ＰＣＲ－ＳＳＣＰ的异常电泳     

Prognostic significance of p53 protein expression in early gastric cancer

Mutations of the p53 tumor suppressor gene have been associated with abnormalities in cell cycle regulation, DNA repair and synthesis, apoptosis, and it has been implicated in the prognosis of advanced gastric cancer. The aim of this study was to evaluate the occurrence of p53 gene mutation and its possible prognostic implications in early gastric cancer. In a retrospective study, we studied 80 patients with early gastric cancer treated surgically between 1982 and 2001. Mutation of p53 gene was investigated in surgical gastric specimens by immunohistochemistry, and results were analyzed in relation to gender, age, macroscopic appearance, size and location of tumor, presence of lymph nodes, Lauren’s histological type, degree of differentiation, and the 5-year survival. The expression of p53 was more frequent among the intestinal type (p = 0.003), the differentiated (p = 0.007), and the macroscopically elevated tumors (p = 0.038). Nevertheless, the isolated expression of p53 was not associated with the 5-year survival, or with the frequency of lymph node involvement. The degree of differentiation was detected as an independent factor related to the outcome of patients (0.044). Significantly shorter survival time was found in p53-negative compared with p53-positive patients, when considering the degree of differentiation of tumors, as assessed by Cox regression analysis (0.049). The association of p53 with the intestinal type, the degree of differentiation and morphological characteristics, may reflect the involvement of chronic inflammatory process underlying early gastric cancer. In this population sample, the expression of p53 alone has no prognostic value for early gastric cancer. However, the significant difference in p53 expression between subgroups of degree of differentiation of tumors can influence post-operative outcome of patients and may be related to possible distinct etiopathogenic subtypes.     

Prognostic significance of the size of cancer nests in metastatic lymph nodes in human esophageal cancers

BACKGROUND: Postoperative survival of patients with esophageal cancers after curative surgery is strongly affected by the presence of lymph node metastasis. The number and location of lymph node metastases have been evaluated and graded, but the clinical significance of their size has not been well investigated. METHODS: Of 322 esophageal cancer patients who underwent curative operations with radical lymph node dissection, 170 (53%) had lymph node metastasis. A total of 784 metastatic lymph nodes were obtained, and the area of the cancer nests was measured microscopically in the cross section. The data from each patient included the area of the largest cancer nest in the positive nodes (Nmax), classified as Na (<4 mm2), Nb (4-25 mm2), Nc (25-100 mm2), or Nd (>100 mm2). RESULTS: The 170 patients were classified according to the Nmax value: Na, 31 (18.2%); Nb, 35 (20.5%); Nc, 49 (28.8%); and Nd, 55 (32.4%). The 5-year survival rate was 77.7% in patients without lymph node metastasis and 35.4% in those with lymph node metastasis. When classified by Nmax, the 5-year survival rate was 77.8% for Na, 63.9% for Nb, 18.8% for Nc, and 12.8% for Nd. There was no significant difference in the survival rate between Na patients and those without lymph node metastasis. Nmax showed significant correlation with the primary tumor size, depth of tumor invasion, and number and location of metastatic lymph nodes, but not with histologic type or primary tumor location. In multivariate analysis, the Nmax value, the number of lymph node metastases and depth of tumor invasion were independent prognostic factors, while the location of the lymph node metastases was not statistically significant. CONCLUSIONS: The area of the largest cancer nest in the lymph nodes was one of the most significant prognostic factors for esophageal cancers. This estimation is objective and reproducible and may be of great importance when deciding the therapeutic modality for patients with esophageal cancers.     

肺癌p16基因纯合缺失,突变,表达及临床意义

目的探讨P16基因的改变与肺癌生物学行为的关系。方法控制正常细胞对肿瘤组织污染后，用聚合酶链反应一单链构型多态性分析（PCR－SSCP）和免疫组织化学法对60例肺癌组织P16基因纯合缺失、突变、表达进行了研究。结果小细胞肺癌无P16基因纯合缺失、突变和蛋白表达异常。非小细胞肺癌P16基因纯合缺失率和突变率分别为40．5％和5．7％且与肿瘤细胞的分化程度、组织类型、转移和预后明显相关。非小细胞肺癌P16蛋白表达缺失率为42．3％，与p16基因纯合缺失有高度的一致性，两者的缺失符合率为76％。结论P16基因异常和失活可能与非小细胞肺癌的组织学类型、分化和预后有一定关系。     

RELATIONSHIP BETWEEN THE MUTATION OF P53 GENE AND INFILTRATION，METASTASIS AND PROGNOSIS OF GASTRIC CARCINOMA

ＲＥＬＡＴＩＯＮＳＨＩＰＢＥＴＷＥＥＮＴＨＥＭＵＴＡＴＩＯＮＯＦＰ５３ＧＥＮＥＡＮＤＩＮＦＩＬＴＲＡＴＩＯＮ，ＭＥＴＡＳＴＡＳＩＳＡＮＤＰＲＯＧＮＯＳＩＳＯＦＧＡＳＴＲＩＣＣＡＲＣＩＮＯＭＡＸｉｎＹａｎ辛彦；ＺｈａｏＦｅｎｇｋａｉ赵凤凯；ＷｕＤｏｎｇ...     

200例食管癌根治术淋巴结清扫的分析

自1987年～1990年对200例食管癌患者进行根治手术并对病理淋巴结分析.其中肿瘤<3cm者18例,无1例淋巴结转移.肿瘤在3cm～5cm者100例,左下肺静脉淋巴结10例(10％)转移,左肺动脉淋巴结无1例转移.胃左动脉淋巴结有20例(20％)转移,气管隆突淋巴结14例(14％)转移,肿瘤5cm～7cm长度者64例中,左下肺静脉淋巴结11例(17％)有转移,左肺动脉淋巴结无1例转移.胃左动脉淋巴结25例(39％)有转移,气管隆突淋巴结34例(53％)有转移.8cm以上病例18例,其中左下肺静脉淋巴结4例(22％)有转移,胃左淋巴结18例(100％)有转移,气管隆突淋巴结16例(88％)有转移.左肺动脉淋巴结1例(5.8％)转移.结合淋巴结转移规律对手术切除范围作了探讨.