抑癌基因p16和Rb与肺癌早期诊断的临床实验研究

目的　研究肺癌组织中p16和Rb基因失活的比率和失活的机制 ,探讨其与肺癌生物学特性及临床、病理和基因分型诊断的关系。　方法　采用免疫组化、双重原位杂交、PCR、PCR SSCP以及序列分析等方法 ,检测 10 6例肺癌及 2 3例肺良性疾病组织标本抑癌基因p16和Rb的改变。　结果　肺癌细胞p16、Rb在蛋白和mRNA水平的表达明显低于正常肺组织和良性疾病肺组织 ,且与肺癌组织学类型、有无淋巴结转移以及临床病理分期密切相关。较早期肺癌 (I、II期 )病例即有较为显著的抑癌基因p16和Rb的失活 (32 6 %和 2 8 3% ) ;非小细胞肺癌以p16基因失活为主 (5 0 1% ) ,小细胞肺癌以Rb基因失活为主 (88 2 % )。p16基因失活的主要机制有纯合缺失、甲基化和点突变。　结论　抑癌基因p16和Rb在肺癌发生发展中起重要作用 ;p16和Rb基因的失活 ,有可能是肺癌发生的早期始动环节 ,对肺癌的早期诊断有重要意义 ;本研究结果提示 ,有可能建立肺癌基因分型诊断新模式。     

肺癌组织中p16基因mRNA表达及其临床意义

目的　检测肺癌组织中p16基因mRNA的表达情况 ,探讨p16基因在肺癌发生发展过程中的作用。方法　应用逆转录 聚合酶链反应 (RT PCR)方法检测肺癌组织中p16基因mRNA的表达。结果　肺良性疾病组织、癌周正常肺组织p16基因mRNA表达高于肺癌组织 ,差异有显著性 (P分别 <0 .0 5 ) ;小细胞肺癌p16基因mRNA阳性率 (10 0 %)高于非小细胞肺癌 (4 6.0 %)P <0 .0 5 ;临床Ⅰ、Ⅱ期p16基因mRNA阳性率 (75 .0 %)高于临床Ⅲ、Ⅳ期 (3 4.1%) ,P <0 .0 5 ;无淋巴结转移的病例p16基因mRNA阳性率 (73 .3 %)高于有淋巴结转移的病例 (3 3 .3 %) ,P <0 .0 5 ;高、中分化病例组p16基因mRNA表达阳性率 (5 4.5 %)与低分化病例组 (4 4 .0 %)之间差异无显著性 (P >0 .0 5 )。结论　p16基因的异常改变可能参与了非小细胞肺癌发生发展过程 ,p16基因mRNA的表达检测作为一种辅助指标。     

进展期胃癌 No.12淋巴结转移规律对手术范围的指导意义

目的分析进展期胃癌 No.12淋巴结的转移规律,为肝十二指肠韧带淋巴结切除范围提供参考依据。方法选择2013年1月至2014年12月行根治性切除手术的进展期胃癌217例,记录每例病人的淋巴结总数,计算总体淋巴结转移率及 No.12a,12p 和 No.12b 淋巴结转移率,并分析No.12p 淋巴结转移的相关危险因素。结果217例手术标本共检出淋巴结9490枚(16~107枚),平均(43.73±14.05)枚/例。217例中164例有淋巴结转移,总体淋巴结转移率为75.58%,其中61例(28.11%)有 No.12淋巴结转移。61例 No.12淋巴结转移病例中,50例(23.04%)发现 No.12a 淋巴结转移,26例(11.98%)发现 No.12p 淋巴结转移,仅 1例(0.46%)发现 No.12b 淋巴结转移。No.12p 淋巴结转移的相关危险因素有肿瘤部位、肿瘤侵犯深度、No.5及 No.12a 淋巴结转移。结论进展期胃癌的 No.12淋巴结转移有明显规律,有助于指导肝十二指肠韧带淋巴结切除范围。     

原发性肝癌患者原发灶和转移灶中p16状态的比较

目的　探讨p16基因在原发性肝癌发生、转移过程中的动态变化。方法　收集 18例患者原发性肝癌原发灶及远处转移灶石蜡标本 3 6块 ,以PCR SSCP方法检测p16基因exon 2。结果　 18例中p16变异占 2 2 .2 % (4 /18) ,其中 2例仅在转移灶发现 ,另 2例为原发灶和转移灶均发生变异 ,ex on 2缺失占 11.1% (2 /18) ,突变占 11.1% (2 /18) ,但该 4例变异均发生在 7例原发性肝癌转移同时伴有复发的患者 (5 7.1% ,4/7) ,显著高于仅转移无复发患者 (0 /11) (P <0 .0 5 )。 4例p16变异病例的术后复发转移时间 (7个月 )显著早于 14例无变异者 (2 1个月 ) (P <0 .0 5 )。结论　在原发性肝癌的复发转移过程中 ,p16变异起重要作用 ;小部分p16变异也可始发于转移灶。     

多排CT对早期胃癌术前评估的价值

目的:探讨多排CT(multidetector-row computed tomography,MDCT)对早期胃癌术前评估的价值.方法:对725例胃癌病人(包括115例早期胃癌)术前行MDCT检查,并将其结果与病理检查结果相对照.结果:MDCT对早期和进展期胃癌的检出率分别为74.8%(86/115)和99.0%(604/610),二者间存在显著差异(P=0.000).MDCT检出的早期胃癌瘤体明显大于未被检出者(2.8 cm比1.6 cm,P=0.000),并且其淋巴结转移率显著高于后者(20.9%比3.4%,P=0.040).MDCT鉴别早期和进展期胃癌的总准确率达94.2%(683/725).在86例MDCT检出原发灶的早期胃癌病人中,59例得到准确分期,而其余27例均被过度分期为T2或T3期,两组在大体类型(P=0.007)和分层方式(P=0.000)间存在显著差异;多因素分析显示仅分层方式与MDCT对早期胃癌T分期的判断准确率相关.MDCT对早期胃癌淋巴结转移判断的敏感度、特异度和准确率分别为73.7%(14/19)、85.4%(82/96)和83.5%(96/115);对<4枚转移淋巴结的判断敏感度为66.7%(10/15),对≥4枚者的敏感度达100.0%(4/4).在MDCT未检出转移淋巴结的5例早期胃癌病人中,其肿瘤均≥2 cm,2例属凹陷型黏膜内癌.1例早期胃癌兼有位于左肝内<1 cm的转移灶未被MDCT检出,其余114例早期胃癌均被准确判断为M0期.结论:MDCT对早期胃癌术前评估的临床应用价值较大,对于被MDCT检出原发灶的早期胃癌病人,由于其淋巴结转移率高且肿瘤较大,不宜行微创治疗.此外,由于多数早期胃癌病人的转移淋巴结少于4枚,且MDCT对其判断的敏感度相对较低,所以在考虑对早期胃癌病人行微创治疗时,仍应高度重视淋巴结转移之相关临床病理因素对淋巴结状况评估的作用.     

p16-nm23-H1蛋白在胃癌及转移淋巴结中的表达

目的观察抑癌基因p16和转移抑制基因nm23-H1蛋白在人胃癌及转移淋巴结中的表达,探讨两者在胃癌转移及预后评估中的作用.方法应用SP免疫组织化学方法检测46例原发性胃癌及69枚转移淋巴结中p16和nm23-H1蛋白表达.结果p16和nm23-H1蛋白在受检原发性胃癌中的阳性表达率分别为17.4%(8/46/)和28.3%(13/46),在转移淋巴结中的阳性率分别为15.9%(11/69)和14.5%(10/69).原发癌伴淋巴结转移组p16的阳性表达率(6.9%)低于不伴淋巴结转移组的阳性率(35.3%),差异具有显著性(P《0.05).原发癌伴淋巴结转移组nm23-H1的阳性表达率(10.3%)低于不伴淋巴结转移组的阳性率(58.8%),差异具有显著性(P《0.01).nm23-H1在乳头状腺癌中的表达率明显高于其他组织学类型(P《0.05).p16和nm23-H1表达与肿瘤大小、部位、浸润深度、Bormann分型、年龄及性别等因素无相关性(P》0.05).p16和nm23-H1在原发性胃癌及转移淋巴结中的表达无相关性(P》0.05).结论p16和nm23-H1基因蛋白对胃癌的发展及淋巴结转移有抑制作用.检测胃癌p16和nm23-H1基因蛋白对评估胃癌生物学行为、预测胃癌淋巴结转移以及预后可能具有一定的价值.     

p16和nm23-H1基因表达与胃癌及淋巴结转移的关系

目的:进一步评估p16和nm23鄄H1基因表达在胃癌中的作用,尤其是与肿瘤淋巴结转移的关系。方法:采用免疫组织化学方法,检测p16和nm23鄄H1基因蛋白在46例原发性胃癌及69枚转移淋巴结中的表达,探索二者表达与胃癌临床病理特征的关系,评估二者作为预测肿瘤转移和临床预后的生物学指标的可能性。结果:p16和nm23鄄H1基因蛋白表达在原发性胃癌中的阳性率分别为17.4%和28.3%,在转移淋巴结中的阳性率分别为15.9%和14.5%。p16表达在伴和不伴淋巴结转移的原发性胃癌中差异显著(P<0.05)。nm23鄄H1在乳头状腺癌中呈明显高表达。p16和nm23鄄H1蛋白表达在原发性胃癌及转移淋巴结中无相关关系。结论:胃癌组织和转移淋巴结中存在p16和nm23鄄H1基因蛋白频繁缺失;p16阳性表达的病人淋巴结转移机会降低;nm23鄄H1基因蛋白表达率在乳头状腺癌中明显高于其他组织学类型;nm23鄄H1表达与胃癌淋巴结转移无关;p16和nm23鄄H1表达调节似无关联,同时检测p16和nm23鄄H1表达不比单纯检测p16表达具有更高预测胃癌淋巴结转移的价值。     

DMBT1基因在上消化道癌组织中的表达及其意义

目的　探讨DMBT1基因转录表达异常在人上消化道癌组织发生、发展中的作用。方法　应用逆转录 聚合酶链反应 (RT PCR)检测 38例食管癌、2 1例贲门癌、2 5例胃癌肿瘤组织及其相应癌旁正常组织中DMBT1mRNA的表达缺失情况。结果　食管癌、贲门癌及胃癌组织中DMBT1mRNA阳性表达缺失率分别为 63 .2 % (2 4 / 38)、52 .4 % (1 1 / 2 1 )及 72 .0 % (1 8/ 2 5) ;伴有淋巴结转移的癌组织中DMBT1表达缺失率均显著高于相应淋巴结无转移的癌组织 (P <0 .0 2 5) ;肿瘤外侵越严重 ,DMBT1mRNA表达缺失率越高 (P <0 .0 2 5)。结论　DMBT1基因表达缺失与上消化道癌侵袭及淋巴结转移密切相关 ,提示该基因在上消化道癌的发生、发展及转移中起一定作用。     

在早期胃癌男性患者中高脂血症与淋巴结转移呈正相关

局限于粘膜或粘膜下层的胃癌称之为早期胃癌,其淋巴结转移率仍分别占2 %～4%和1 5 %～2 0 %。病理学资料提示肿瘤大小、组织类型、淋巴浸润和浸润深度是淋巴结转移的独立性标志,但这些资料不能用于手术前,应寻求术前预测淋巴结转移的因素,在乳腺、前列腺和结肠肿瘤中,其发生率与高脂饮食有关,为此研究早期胃癌病例中术前血清总胆固醇(TC)和甘油三醇(TG)与淋巴结转移的相关性。日本东京大学肿瘤外科于1 987～2 0 0 1年共为3 5 3例早期胃癌和3 2 0例进展期胃癌进行了胃切除,测定其术前TC和TG血清值。凡TC≥2 2 0mg/dL和TG≥1 5 0mg/mL者…     

早期胃癌的内窥镜治疗

胃癌是常见的恶性肿瘤之一,目前手术治疗依然是最有效的治疗手段,但是总的5年术后生存率仍然较低.近10多年来,早期胃癌诊断的比例有所上升,在日本和韩国,早期胃癌占的比例可达40%～50%,欧洲国家约为20%.由于早期胃癌淋巴结转移率明显低于进展期胃癌,所以早期胃癌术后5年生存率远远高于进展期胃癌.所有这些变化,很大程度上归功于内窥镜技术的普及和改进.内窥镜技术的问世和发展要追溯至19世纪中叶.1868年,德国医生库斯莫尔(Kussmaul)用长47 cm、直径13 mm的直的金属管,进行了最原始胃镜的尝试,1881年米库立兹(Mikulicz)等制作了最早的实用型硬性胃镜.     

Genetic alterations of the p16 gene in urothelial carcinoma in Taiwanese patients

OBJECTIVE: To measure changes in the p16 gene (MTS1, a negative regulator of cell-cycle progression at the G1 checkpoint, and a tumour suppressor gene) in urothelial carcinomas (including upper tract urothelial and bladder tumours), and to correlate these measurements with the clinical status of such patients in Taiwan, where renal pelvic tumours comprise 47% of all kidney tumours and are more common than the average worldwide. MATERIALS AND METHODS: Thirty-five upper tract urothelial and 61 bladder tumours were examined for changes in p16. Deletion of the gene was assessed by Southern blot analysis and mutation analysed using polymerase chain reaction-single strand conformation polymorphism, followed by direct sequencing. RESULTS: Of the 61 bladder carcinomas, homozygous deletion of p16 was detected in 12 (20%). However, a homozygous deletion was detected in 11 of 35 (31%) upper tract urothelial carcinomas, a higher frequency than that reported for transitional cell bladder carcinomas. Deletion was detected as frequently in stage I tumours as in late-stage tumours, suggesting that p16 deletion is a relatively early event in urothelial tumorigenesis. No point mutations were noted for p16 in any of the primary urothelial tumours. Most multiple and recurrent tumours and metastatic nodules in individual patients contained identical p16 genetic lesions, confirming that the tumours were probably monoclonal. In addition, there was a high gene dose of p16 in bladder carcinomas from patients with lymph node metastasis. CONCLUSION: Deletion of p16 appears to be a common event in urothelial carcinomas, especially in upper tract urothelial tumours. High levels of p16 were detected in tumours with lymph node metastasis. It seems likely that a high p16 level is associated with carcinomas of advanced stage and grade, and with poor prognosis in patients with such cancers.     

DCC基因201密码子突变与胃癌相关性的研究

目的 :研究胃癌组织中是否存在大肠癌缺失 (deletedincolorectalcancer,DCC)基因 2 0 1密码子点突变及其与胃癌临床病理因素的相关性。方法 :取 5 4例胃癌病人的胃癌组织和癌旁黏膜组织及非胃癌病人的正常胃黏膜组织标本 30份 ,行PCR +限制性片段长度多态性 (restrictionfragmentlengthpolymorphism ,RFLP)分析。 结果 :胃癌组织、癌旁黏膜及正常胃黏膜中DCC基因 2 0 1密码子点突变率分别为 5 9.3%、5 3.7%和 10 %,胃癌组织与癌旁黏膜两者的突变率都明显高于正常胃黏膜 (P     

Concordant loss of MTAP and p16/CDKN2A expression in gastroesophageal carcinogenesis: evidence of homozygous deletion in esophageal noninvasive precursor lesions and therapeutic implications

The gene that encodes methylthioadenosine phosphorylase (MTAP), an enzyme involved in adenine and methionine salvage pathways, is located on chromosome 9p21 telomeric to the p16INK4A/CDKN2A tumor suppressor gene. Inactivation of the p16INK4A/CDKN2A gene occurs by three different mechanisms: hypermethylation of the gene promoter, intragenic mutation coupled with loss of the second allele, and homozygous deletion. Immunohistochemical labeling for the p16INK4A/CDKN2A gene product parallels gene status but does not elucidate the mechanism of gene inactivation. Since the MTAP gene is often co-deleted with p16INK4A/CDKN2A, concurrent immunolabeling for both proteins can identify cases with homozygous p16INK4A/CDKN2A gene deletion. MTAP loss itself has therapeutic implications since it may confer selective sensitivity to inhibitors of de novo purine biosynthesis, such as L-alanosine. Twelve tissue microarrays were constructed from 92 cases of Barrett-associated adenocarcinomas and precursor lesions and 112 cases of gastric adenocarcinoma and precursor lesions comprising 1161 individual cores. Multiple cores were arrayed from any given case, and when available, included the entire histologic spectrum of intestinal metaplasia-dysplasia-carcinoma. Tissue microarrays were labeled with monoclonal antibodies against MTAP protein (clone 6.9, Salmedix, Inc) and p16 (clone 16P07, Neomarkers). Complete loss of labeling was considered negative, while any labeling (p16: nuclear; MTAP: cytoplasmic and nuclear) was considered positive. Loss of MTAP labeling occurred exclusively in conjunction with loss of p16 labeling, confirming that the previous findings from this group that concurrent loss of MTAP and p16 labeling is a surrogate marker of 9p21 homozygous deletions. Complete loss of MTAP and p16 was seen in 4 of 25 (16%) patients with Barrett's esophagus, 4 of 18 (22%) with low-grade dysplasia, 5 of 39 (13%) with high-grade dysplasia, 17 of 78 (22%) with invasive adenocarcinoma, and 8 of 36 (22%) of metastases. There were 7 cases of esophageal adenocarcinoma with loss of both MTAP and p16 for which precursor lesions were available. In 6 on these 7 cases (85%), the precursor lesion(s) had loss of both MTAP and p16. Lack of MTAP and p16 expression was seen in 11 of 106 (10%) cases of gastric adenocarcinoma. All metaplastic (30 biopsies from 20 cases) and dysplastic (15 biopsies from 13 cases) gastric tissues had both intact MTAP and p16INK4A/CDKN2A gene products. No precursor lesions were available from the gastric cancers that had loss of both MTAP and p16. Two benign gastric hyperplastic polyps also had intact p16 and MTAP. Concurrent MTAP and p16 loss detected by immunohistochemistry can serve as a convenient surrogate for p16INK4A/CDKN2A gene homozygous deletion in archival tissues. Inactivation of p16INK4A/CDKN2A by homozygous deletion appears to be an early event in Barrett carcinogenesis, occurring in noninvasive precursor lesions, including nondysplastic Barrett mucosa, in subsets of cases. In the absence of MTAP, cells depend exclusively on the de novo synthesis pathway for production of adenosine. This loss of MTAP during 9p21 homozygous deletion might be exploited therapeutically using de novo purine synthesis antimetabolites to treat a subset of invasive gastroesophageal adenocarcinomas and esophageal precursor lesions.     

进展期胃癌的淋巴结转移特点及其临床意义

目的探讨进展期胃癌的淋巴结转移特点及临床意义。方法对2002年4月至2003年7月期间进行胃癌根治淋巴结清扫手术的91例患者的手术切除标本进行解剖，收集切除的淋巴结，逐枚进行病理组织学和免疫组织化学检查，判断淋巴结是否转移并计算淋巴结转移率。分析淋巴结转移率与肿瘤大小、TNM分期、Borrmann分型、肿瘤部位和淋巴结清扫范围等方面的关系。结果91例胃癌患者中淋巴结转移阳性63例（69．2％）。共收获3149枚淋巴结，平均每例34．6枚。肿瘤直径小于3cm者淋巴结转移率较3cm以上者低（P〈0．05）。TNM分期中Ⅲa和Ⅳ期患者淋巴结转移率均为100％，其转移度在30．3％～58．4％之间，较Ⅰ、Ⅱ期者高（P〈0．001）；Borrmann分型中Ⅲ型病例的淋巴结转移率（79．6％）较其他型患者高，而Ⅳ型患者淋巴结转移度（35．3％）最高（P〈0．05）。施行D3淋巴结清扫手术患者的淋巴结转移率和转移度（88．2％、38．0％）均高于D1、D2术患者（P〈0．05）。17例（18．7％）患者常规病理检查发现有183枚淋巴结微转移，肿瘤各部位与淋巴结微转移的关系差异无统计学意义（P〉0．05）。近端胃癌淋巴结转移主要在第1、2、3、5、7、8、9、12、13和16组，以8组转移度为最高（68．1％）；中部胃癌淋巴结转移主要在第1、3、7、12、13和16组，其中最高转移度为第3组（47．6％）；远侧胃癌淋巴结转移主要见于1、2．3、5、6、12、13和16组，其中第16组转移度为最高（83．3％）。结论淋巴结转移率和转移度与胃癌的恶性程度密切相关，因此D3淋巴结清扫手术对某些进展期胃癌患者值得考虑使用。     

胃癌淋巴转移规律与淋巴结清扫范围的分析(附326例报告)

目的 探讨胃癌淋巴结转称规律和胃癌根治术的淋巴清扫范围。方法 １９９０年～１９９９年行Ｄ２、Ｄ３、Ｄ３淋巴结廓清术加腹主动脉旁淋巴结廓汪术（Ｄ３加ＰＡＬ）的胃癌患者３２６例,对期临床资料进行回顾性分析。结果 本组总的淋巴结转移率６９．９％,早期与进展期胃癌淋巴结转移率分别为１５．４％和７７．４％。肿瘤浸润深度达Ｔ１的患者,淋巴结转移主要局限于Ｎ１;达Ｔ２的患者淋巴结转移至Ｎ３、Ｔ４的ＫＫＨＮＦＴＪ     

Appropriate lymph node dissection for early gastric cancer based on lymph node metastases

BACKGROUND: Lymph node dissection in patients with early gastric cancer is controversial because lymph node metastases are much less common than in advanced cancer. Therefore, routine extensive lymph node dissection with wide resection of the stomach may be excessive, and an appropriate lymph node dissection procedure in patients with early gastric cancer should be established. METHODS: Retrospectively, 588 consecutive patients with early gastric cancer were analyzed by univariate and multivariate analysis to predict lymph node metastases with clinicopathologic variables. The sites and rates of lymph node metastases for each tumor location were mapped. RESULTS: In early gastric cancer, depth of invasion was an independent predictive factor of lymph node metastases. In cancer confined to the mucosa, however, tumor diameter was the only predictive factor. In contrast, tumor diameter, macroscopic appearance, and histologic type were not predictive factors in early gastric cancers invading the submucosa. In mucosal cancer, metastasis to lymph nodes was confined to the paragastric lymph nodes on the same side of the stomach as the tumor. In submucosal cancer, the incidence of lymph node metastasis was 2% to 17% in group 1 and 1% to 3% in group 2 lymph nodes. CONCLUSIONS: In mucosal cancer, lymph node dissection is unnecessary for tumors measuring less than 30 mm, and limited lymph node dissection with local gastrectomy is appropriate when tumor diameters are 30 mm or greater. In submucosal cancer, gastrectomy with dissection of group 1 and some group 2 lymph nodes should be sufficient to remove all nodal metastases.     

动静脉联合给药的FLEOX新辅助化疗加营养支持提高晚期胃癌可切除率

目的总结动静脉联合给药的FLEOX新辅助化疗加营养支持对以淋巴结转移为主的晚期胃癌的手术可切除率。方法对术前CT检查发现伴有严重的第3、7、9、12组淋巴结转移、或第14、16组淋巴结转移而难以切除的50例晚期胃癌患者进行新辅助化疗：氟尿嘧啶（5．FU）370mg／m^2，静滴，第1～5天；亚叶酸钙200mg静滴，第1～5天；足叶乙苷80mg／m^2与奥沙利铂120mg／m^2经动脉注射，第6、20天；每5周重复1次。其中12例伴有中、重度营养不良者酌情进行肠外、肠内营养支持，状况好转后进行化疗，以使患者获得手术切除的机会。结果50例晚期胃癌患者的影像学及组织学评价有效率（CR加PR）为84．0％；12例伴营养不良的病例在化疗结束、拟行手术前体重均较入院时明显增加，血清白蛋白等营养指标恢复正常。手术切除率为78．0％，全组均成功进行了胃次全切除、全胃或联合脏器切除和D2＋α、D3淋巴结清扫术。结论动静脉联合给药的FLEOX新辅助化疗加合理的营养支持对以淋巴结转移为主的晚期胃癌具有满意的治疗效果。     

人非小细胞肺癌P16基因突变研究

目的探讨ｐ１６基因缺失和突变与人非小细胞肺癌发生、发展的关系。方法应用多重ＰＣＲ、ＳＳＣＰ分析及ＤＮＡ序列分析技术，对４５例人非小细胞肺癌组织中ｐ１６基因外显子１和外显子２进行基因缺失和突变分析。结果４５例肺癌样品中共检出１９例ｐ１６基因缺失，总的缺失率为４２．２％（１９／４５）。其中纯合型缺失８例（１７．８％），半合型缺失１１例（２４．４％）；外显子１缺失７例（１５．６％），外显子２缺失１２例（２６．７％）；ｐ１６基因外显子２的突变检出率为３１．１％（１４／４５）；ＤＮＡ序列分析显示ｐ１６基因７２位密码子无义突变７例，７５位密码子错义突变７例。结论ｐ１６基因的缺失和突变可能与人非小细胞肺癌的发生、发展有关。     

乳腺癌细胞p16基因的研究

目的 探讨Ｐ１６基因在乳腺癌中的突变形式和频率以及有效的检测手段。方法 采用细胞２,反复贴壁法纯化人乳腺癌细胞、经多聚酶链反应－单链构象多态性（ＰＣＲ－ＳＳＣＰ）分析技术。对１４例纯化乳腺癌细胞标本,１４例新鲜未纯化标本和２７例石蜡包埋标本及相应的癌旁乳腺组织标本的这６基因突变进行了对比性研究。结果 纯化的癌细胞组Ｐ１６基因突变率为４２．９％,而新鲜未纯化细胞组、石蜡包埋细胞组及癌旁乳腺细胞组的Ｐ     

胃癌及其癌旁病变中p16、nm23-H_l基因蛋白的表达及意义

目的:应用免疫组化方法探讨p16蛋白在胃癌发生中的作用.方法:应用免疫组化方法对57例胃癌切除标本进行p16蛋白和nm23-H_1基因产物的表达检测.结果:57例胃癌中p16蛋白表达阳性率为40/57(70.2%),显著低于癌旁正常胃粘膜(P<0.01).胃癌高分化组的阳性率显著高于低分化组(P