Association of cyclin D1, p16 and retinoblastoma protein expressions with prognosis and metastasis of gallbladder carcinoma

AIM: To investigate the role of cyclin D1, p16 and retinoblastoma in cancerous process of gallbladder carcinomas and to assess the relation between cyclin D1, p16, Rb and the biological characteristics of gallbladder carcinoma. METHODS: Forty-one gallbladder carcinoma, 7 gallbladder adenoma and 14 chronic cholecystitis specimens were immunohistochemically and histopathologically investigated for the relation of cyclin D1, p16 and Rb with Nevin staging and pathologic grading. RESULTS: The expression rates of abnormal cyclin Dl in gallbladder carcinoma (68.3%)and gallbladder adenoma (57.1%) were significantly higher than those in chronic cholecystitis (7.1%) (P<0.05). No significant difference was found both among the pathological grades G1, G2 and G3 and among Nevin stagings S1-S2, S3 and S4-S5 of gallbladder carcinoma. The positive rates of p16 (48.8%) and Rb (58.5%) in gallbladder carcinoma were significantly lower compared to those in adenoma (100.0%) and cholecystitis (100.0%) (P<0.05). The positive rates of p16 and Rb in Nevin stagings S1-S2 (80.0% and 90.0%) and S3 (46.2% and 61.5%) gallbladder carcinomas were significantly higher than those in S4-S5(33.3% and 38.8%) (P<0.05), and those in pathologic grades G1(54.5% and 81.8%) and G2 (50.0% and 62.5%) gallbladder carcinoma were significantly higher than those in G3 (28.6% and 35.7%) (P<0.05). The protein expression of p16 and Rb had a negative-correlation in gallbladder carcinoma (r= -0.2993, P<0.05), and this negative-correlation was correlated with Nevin staging (P<0.05). Moreover, the protein expression of p16 and cyclin Dl had a negative-correlation in gallbladder carcinoma (r = -0.9417, P<0.05). CONCLUSION: Cyclin Dl may play a role in the early stage of gallbladder carcinoma. Mutation of p16 and Rb genes might be correlated with progression of gallbladder carcinoma. Analysis of p16 and Rb can estimate the prognosis of gallbladder carcinoma. Expression of p16 and Rb may be correlated with Nevin staging and pathologic grading in gallbladder carcinoma.

Interaction among Rb/p16, Rb/E2F1 and HDAC1 Proteins in Gallbladder Carcinoma

The mechanism and interaction among Rb/p16, Rb/E2F1 and HDAC1 proteins in gallbladder carcinoma were investigated. By using the immunoprecipitation method, the interactions among Rb, p16, E2F1, HDAC1 proteins in gallbladder carcinoma cell line （Mz-ChA-1） were studied. It was found that there were Rb and E2F1 proteins in the precipitates with anti-HDAC1, and there were HDAC1 and E2F1 proteins in the precipitate with anti-Rb. It was concluded that there are specific interactions among Rb, HDAC1 and E2F1 proteins in gallbladder carcinoma, indicating the existence of the direct Rb/E2F1/HDAC1 signal transduction pathway. There is no direct relationship between p16 proteins with Rb, HDAC1, and E2F1 proteins.

Expressions of p16 and FHIT Proteins During Esophageal Carcinomatous Development in High Incidence Area of Esophageal Carcinoma

Objective： To detect the changes of p16 and FHIT and investigate their relationship in esophageal squamous cell carcinoma development by measuring their expression levels in normal squamous epithelium tissue, mild, moderate, severe dysplasia lesions, carcinoma in situ and invasive squamous cell carcinomas. Methods： Expressions of p16 protein and FHIT protein were detected and analyzed in 17 cases of normal squamous epithelium, 16 cases of mild dysplasia, 16 cases of moderate dysplasia, 17 cases of severe dysplasia, 10 cases of carcinoma in situ, and 18 cases of esophageal squamous cell carcinoma by immunohistochemical method. Results： With increasing histopathologic grades, the expressions of pl6 and FHIT became gradually lower. There was no remarkable difference of p16 and FHIT expressions between the normal and mild dysplasia group （P〉0.05）, but the differences between the normal and other groups were all significant （P〈0.05）. There was no remarkable difference among the squamous cell carcinoma group, the moderate and severe dysplasia groups, and the carcinoma in situ group （P〉0.05）, but significant differences existed in the expressions of p16 and FHIT proteins between the squamous cell carcinoma and the normal groups, and between the squamous cell carcinoma and the mild dysplasia groups （P〈0.05）. There was an association of descending trend between p16 and FHIT protein expressions. Conclusion： Reduced expressions of pl6 and/or FHIT proteins possible play an important role in the early occurrence of esophageal cancer. There was a positive correlation between the expressions of p16 and FHIT proteins.

EXPRESSION AND SIGNIFICANCE OF ONCOPROTEIN p16 AND FOS IN OSTEOSARCOMA

Objective: To investigate p16, C-fos protein expression and their relationships in osteosarcoma. Methods: Immunohistochemical technique (SABC) was used to detect p16 and C-fos protein expression in 41 cases of osteosarcoma. Results: The positive rates of p16 and C-fos protein expression were 51.2% and 82.9% respectively. Their expression was not correlated to pathological subtype, but correlated to clinic grade, and the latter was associated with tumor metastasis. There was a negative correlation between p16 and C-fos protein expression. Conclusion: The alteration of p16 and C-fos protein expression may be related to the tumorigenesis and development of osteosarcoma, and C-fos proteins may take part in osteosarcoma metastasis. These data will offer useful helpness to determine the prognosis of osteosarcoma.

EXPRESSION OF p16,CYCLIN D1 AND RB PROTEIN IN GASTRIC CARCINOMA AND PREMALIGNANT LESIONS

Objective: To investigate the expression of p16, cyclin D1 and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP immunohistochemical methods, the expression of pl6, cyclin D1 and Rb proteins was detected in 10 specimens of normal gastric mucosa, 15 specimens of dysplastic gastric mucosa, 15 specimens of intestinal metaplasia gastric mucosa, 30 specimens of gastric carcinoma. The clinical characteristics of the 30 patients with gastric carcinoma were analysed to explore the relationship between the parameter detected and biological action of gastric cancer. Results: Expression of p16 protein was detected in 90% of normal gastric mucosa, 86.67% of dysplastic gastric mucosa, 86.67% of intestinal metaplasia gastric mucosa, 36.67% of gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.01). Expression of cyclin D1 protein was detected in 10% of normal gastric mucosa, 20% of dysplastic gastric mucosa, 20% of intestinal metaplasia gastric mucosa, 53.33% of gastric carcinoma. The positive rate of cyclin D1, protein expression in gastric carcinoma is significantly higher than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.05). Expression of Rb protein was detected in 90% of normal gastric mucosa, 80% of dysplastic gastric mucosa, 80% of intestinal metaplasia gastric mucosa, 50% of gastric carcinoma. The positive rate of Rb protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa (P<0.05). The expression of p16, cyclin D1 gene were associated with the degree of differentiation of gastric carcinoma, lymphnodes metastasis and distant metastasis. Conclusion: p16, Cyclin D1 and Rb gene play important role in gastric carcinoma genesis. The expression of p16, cyclin D1 and Rb gene have some value to the diagnosis at earlier stage of gastric cancer. Detection of expression of p16, cyclin D1 gene would be helpful to judge the prognosis of gastric cancer.

Diagnostic value of HPV and P16 protein in patients with HSIL and prognosis

Objective: To investigate the diagnostic value and prognostic value of HPV and P16 protein in patients with HSIL and to provide a reference for the clinical diagnosis and assessment of the prognosis of patients with HSIL. Methods: The surgical treatment of HSIL patients from January 2013 to January 2015 in our hospital were selected. All patients were routinely tested for HPV and P16 protein, All patients were followed up for 1 year. Patients were divided into progressive group and quiescent group according to whether the disease progressed one year after surgery. Preoperative HPV and P16 protein levels were compared between the two groups. Using receiver operating curve (ROC curve) Analysis of HPV diagnostic value of HSIL. The levels of HPV and P16 protein in the two groups were analyzed and compared. Results: The quantitative level of high-risk HPV-DNA after LEEP was significantly lower than that before operation. The level of P16 protein in preoperative patients was higher than that before operation, and the difference was statistically significant. There were 21 patients in the postoperative progression group, and the average HPV-DNA content in the patients in the progression group was higher than that in the control group within one year after operation. The difference was statistically significant. The P16 protein level in patients in advanced group was significantly higher than that in resting group. Preoperative HPV-DNA levels and P16 protein levels in patients with progressive disease were significantly higher than those in still group. ROC curve analysis showed that the cut-off value of 2.441, HPV-DNA prediction of HSIL patients one year after the recurrence of the sensitivity was 95.12%, the specificity was 76.16%, under the curve area of 0.878;7.4 cut-off value, P16 The predictive value of HSIL patients recurrence after 1 year was 71.95%, specificity was 66.67%, and the area under the curve was 0.753. The recurrence group HPV-DNA content and P16 protein level showed a significant positive correlation, with statistical significance. Conclusions: LEEP can reduce the postoperative levels of HPV and P16 protein in patients with HSIL. The HPV and P16 protein levels are of high value for the early diagnosis of HSIL and the prediction of postoperative disease progression.

The Change and Implication of p16 Protein in CA and Its Cancerization

Objective : To investigate the role and clinical significance of p16 protein in Condyloma Acuminatum (CA) and its cancerization. Methods: The expression of p16 protein was tested in 33 CA samples and 7 cancerized CA samples by immunohistochemical assays. Results: There was abnormal expression of p16 protein in CA and cancerized CA, mainly major protein expression. The p16 protein expresseed in different locations in different cases was as follows: In basal layer cells in normal cuits; in spinous layer, granular layer and stratum corneum layer cells in CA;in keratin pearl peripheral and spinous layer cells in cancerized CA. Conclusion.. There was major expression of p16 protein in CA and cancerized CA, and these protein of the two groups might not naturally be the same. Our study indicated that in clinical practice, when major p16 protein expression in CA occurs, it's risk of cancerization shoud be suspected.

胰腺癌中p16基因甲基化改变及其蛋白表达分析

目的探讨胰腺癌与癌旁组织中p16基因启动子区异常甲基化的改变及其蛋白表达的特点,以及其与胰腺癌发生发展的关系。方法分别采用免疫组化SP法及甲基化特异PCR(MSP)检测46例人胰腺癌和癌旁组织中p16基因表达及其甲基化的水平,并结合临床资料进行分析。结果胰腺癌中p16蛋白表达率为41.3%(19/46),而癌旁组织表达率为95.7%(44/46),两者有差异显著性(P<0.01)。p16蛋白阳性的19例胰腺癌标本中均未检出基因甲基化;p16蛋白缺失的27例标本中有18例检出基因甲基化,甲基化率为39.1%。p16基因甲基化与蛋白缺失有明显关系(P<0.05)。p16基因表达及其启动子区甲基化的发生率与胰腺癌的大小,患者性别?年龄的差异无显著意义(P>0.05),但与组织分化程度?淋巴结转移?PTNM分期有显著意义(P<0.05)。结论p16基因启动子的异常甲基化可影响p16蛋白的表达,它们与胰腺癌的发生发展有关;p16甲基化和蛋白表达可能成为胰腺癌诊断及预后的候选标志物之一。

子宫内膜癌中p^(16)蛋白表达的免疫组化检测及其临床意义的研究

目的：探讨ｐ１６蛋白在子宫内膜癌中的表达及其临床意义。方法：应用抗ｐ１６抑癌基因的表达产物ｐ１６蛋白的单克隆抗体对５０份子宫内膜癌常规石蜡标本进行ｐ１６蛋白的免疫组化测定。结果：ｐ１６蛋白的表达广泛见于正常子宫内膜腺体、平滑肌和部分病例的癌组织中，阳性部位主要在细胞浆内。ｐ１６蛋白在子宫内膜癌表达的阳性率仅为４８．００％（２４／５０），其表达与子宫内膜癌的细胞分级、转移及患者预后有关（Ｐ＜０．０５），ｐ１６蛋白阴性者子宫内膜癌细胞分化程度低，易转移，患者预后差。结论：ｐ１６蛋白作为细胞周期的反向调节因子具有抑制细胞增殖的作用，ｐ１６抑癌基因的突变或缺失导致ｐ１６蛋白合成障碍，可引起细胞无限制性生长，即恶变。对子宫内膜癌中ｐ１６蛋白表达的测定有助于确定肿瘤的细胞分化程度，判断其侵蚀、转移的能力，并估计患者的预后。

星形细胞瘤p16、Rb、cyclinD1、EGFR表达和DNA含量测定

目的 :探讨 p16、Rb、cyclinD1和EGFR在星形细胞肿瘤发生、发展中的作用及其与预后的关系。 方法 :免疫组化染色采用即用型S P法 ,用图像分析系统对 80例星形细胞肿瘤瘤细胞进行DNA含量测定。结果 :80例星形细胞肿瘤 :p16、Rb、cyclinD1和EGFR的阳性率分别为 43 8%、71 3%、5 5 0 %和 85 0 % ,4种蛋白阳性率及DNA含量与组织学分级均有统计学意义 ;p16、Rb、cyclinD1阳性率和瘤细胞DNA含量与预后有关 ,EGFR阳性率与预后无关 ;Rb失表达时 ,p16表达增强。 结论 :p16和Rb在抑制星形细胞肿瘤的生长及EGFR和cyclinD1促使其生长中起着重要作用 ,p16表达同DNA含量相结合评估星形细胞瘤预后有一定价值。

P^(16)抑癌基因产物在肺癌中的表达及临床意义

研究P16在肺癌中的表达与临床病理的关系。用免疫组织化学ABC法检测60例肺癌石蜡标本P16蛋白的表达水平。结果：8例小细胞肺癌P16蛋白的阳性表达率为100％。52例非小细胞肺癌P16蛋白的阳性表达率为57．6％，其中伴有淋巴结转移的肺癌P16蛋白的阳性表达率（18．1％）显著低于无淋巴结转移者（P16阳性表达率为86．6％，P＜0．01），低分化肺癌P16蛋白的阳性表达率（30％）显著低于中、高分化肺癌P16蛋白的阳性表达率（75％），P＜0．05。P16蛋白表达阳性的病人的3a生存率为64．8％。而P16蛋白表达阴性者其3a生存率仅20．3％（P＜0．05）。P16蛋白的表达与病人年龄、性别无关。结论：P16蛋白表达与肺癌组织类型、分化程度及转移有关。P16蛋白的状态可作为判断非小细胞肺癌预后的指标。

P21^(ras)、P16在大肠癌中的表达及临床意义

目的探讨癌基因P21^(ras)及抑癌基因P16与大肠癌的关系。方法应用免疫组化SP法分析、研究了P21^(ras)蛋白、P16蛋白在80例大肠癌、20例大肠腺瘤及20例正常大肠组织中的表达。结果①P21^(ras)在前二者中的阳性表达率分别为70.1％(57/80)和65％(13/20),明显高于在正常组织中的30％(6/20),其比较具有显著性差异(x^2=17.66、P<0.005;x^2=5.23、P<0.05);P16在大肠癌中的阳性表达率为36.3％(29/80)低于在腺瘤及正常组织中的65％(13/20)和75％(15/20),其比较亦具有显著性差异。②P21^(ras)、P16的阳性表达率在大肠癌患者的年龄、性别及肿瘤大小方面无显著性差异,而与肿瘤的临床Dukes分期(x^2=6.20、P<0.025;x^2=6.25、P<0.05)、有无淋巴结转移及术后5a生存率密切相关。③P21^(ras)在不同的大肠癌组织病理类型中,其表达率无显著性差异;P16的阳性表达率随着肿瘤浸润深度的增加有下降趋势,但无统计学意义。④在80例大肠癌患者中,P21^(ras)阳性而P16阴性者比率高于其他三者,而且这类大肠癌患者的术后5a生存率下降。结论大肠癌的发生、发展,是由包括癌基因、抑癌基因在内的多种因素作用的结果;在临床工作中联合检测P21^(ras)及P16蛋白在大肠癌中的表达水平,对我们估计患者的病情、推测其预后有指导性意义。

P16蛋白在子宫颈上皮内瘤变中表达意义与高危型HPV感染的相关性分析

目的:研究P16蛋白在宫颈上皮内瘤变(CIN)中表达的意义,探讨其与高危型人类乳头状瘤病毒(HPV)感染的相关性,以期用P16蛋白的表达预测CIN进展。方法:收集大连大学附属医院2009年1月至2011年5月宫颈活检及手术切除标本137例,免疫组织化学方法检测P16蛋白的表达并评分,HC2方法检测高危型HPV-DNA,并对数据进行分析。结果:P16蛋白表达在慢性子宫颈炎伴鳞状上皮化生中均阴性(0/40),CINⅠ阳性90.91%(20/22),CINⅡ阳性为95.00%(19/20),CINⅢ阳性为100.00%(25/25),浸润性鳞癌阳性为100.00%(30/30)。在慢性子宫颈炎伴鳞化中高危型HPV阳性1例,CINⅠ12例,CINⅡ14例,CINⅢ22例,浸润性鳞癌29例。CIN中感染高危型HPV的病例,P16蛋白均呈阳性表达。结论:P16蛋白可作为区分子宫颈癌及癌前病变与良性反应性增生的标记物,其表达的分层现象能够很好的反映出CIN的分级,P16蛋白阳性表达的评分有助于区分出有高危发展倾向的CIN。

胃癌患者P^(16)和P^(53)蛋白的表达及其相互关系

目的 探讨P16、P53 基因产物在胃癌中表达的生物学意义及其相互关系。方法 用辣根酶标记链霉卵白素免疫组化法对 33例胃癌的临床病理特征进行分析 ,同时与 17例癌旁和 13例正常胃粘膜中P16和P53 蛋白的表达进行了比较。结果 胃癌患者P16蛋白阳性表达率明显高于正常胃粘膜 (P <0 .0 5 ) ,伴淋巴结转移的胃癌阳性细胞密度高于未转移者 (P <0 .0 5 )。P53 蛋白在正常胃粘膜未见表达 ,胃癌中P53蛋白阳性表达显著高于癌旁组织 (P <0 .0 5 )。P53 与P16在胃癌中共同表达 10例 (30 .30 % ) ,P53 和P16蛋白表达与胃癌的病理学分期、分化程度无关。结论 P16基因异常有促进胃癌转移的效应 ,这对判定胃癌患者的预后有一定的指导意义。P53 与P16在胃癌中有协同作用 ,二者异常表达参与胃癌的发生与发展。

P^(16)、P^(15)基因蛋白与葡萄胎恶变关系探讨

目的 探讨P16、P15基因蛋白与葡萄胎恶变的关系。方法 采用免疫组化PV90 0 0方法对 4 0例葡萄胎和 2 5例早孕患者绒毛P16、P15蛋白进行检测。结果 早孕绒毛组织中P16、P15基因蛋白表达均阳性。葡萄胎中P16、P15基因蛋白阴性表达率分别为 4 2 5 %、30 % ,与早孕绒毛组织相比 ,差异有显著性 (P均 <0 0 5 )。葡萄胎恶变组 (7例 )P16、P15基因蛋白表达均阴性者 4例 ,占 5 7 1% ,高于无恶变组的 18.2 % (6 / 33) ,差异有显著性 (P <0 0 5 ) ;恶变组中 ,清宫前子宫大于妊娠月份 ,同时发生黄素囊肿且囊肿 >6cm ,清宫后人绒毛膜促性腺激素 (β HCG)持续 2个月后消退者 ,其P16、P15基因蛋白联合阴性率高于非恶变组 ,差异有显著性 (P <0 0 5 )。结论 葡萄胎的发生、发展与P16、P15基因蛋白缺失有关。P16、P15基因蛋白缺失有望成为预测葡萄胎恶变的指标。

肺癌组织中P^(16)蛋白与血管内皮生长因子表达的临床意义

采用 SABC免疫组织化学方法检测了 71例肺癌患者 (肺癌组 )癌组织中 P1 6蛋白和血管内皮生长因子(VEGF)的表达情况 ,并与 2 0例肺良性病变患者 (对照组 )比较。结果肺癌组的 P1 6 蛋白阳性率为 5 3.5 2 % ,明显低于对照组 (90 % ) ,P<0 .0 1;有淋巴结转移者的 P1 6蛋白阳性率显著低于无淋巴结转移者 ;肺癌分期为 ～ 期者 P1 6蛋白阳性率显著低于 ～ 期者。肺癌组 VEGF阳性率为 71.83% ,明显高于对照组 (2 0 % ) ,P<0 .0 1;吸烟量少者VEGF阳性率显著高于吸烟量多者 ,肿瘤低分化者显著高于高分化者 ,有淋巴结转移者显著高于无淋巴结转移者 ,肺癌为 ～ 期者显著高于 ～ 期者。证实肺癌中 P1 6 蛋白与 VEGF呈负相关 ;P1 6 蛋白及

细胞周期相关蛋白CyclinD1、p16在大肠癌中的表达及其意义

目的:探讨细胞周期调控因子在大肠癌中的表达及其与大肠癌临床病理特征的关系。方法:应用免疫组化SP法对70例大肠癌组织及距癌灶3cm以外的癌旁组织、10cm以外的正常组织中CyclinD1和p16进行检测。结果:CyclinD1在大肠癌中过度表达为36/70(51.4%)并与肿瘤的分化程度呈反比,有淋巴结转移的大肠癌,其CyclinD1的阳性率为70.0%,无淋巴结转移的大肠癌阳性率为44.0%,两者相比差异有显著性(P<0.05)。p16在大肠癌中为低表达33/70(47.1%),癌旁组织和正常组织中p16的表达分别为57.1%和71.4%。CyclinD1与p16呈负相关关系(P<0.05)。结论:CyclinD1的过度表达与肿瘤的分化程度、淋巴结转移密切相关;CyclinD1的过度表达和p16的低表达在大肠癌发生中起协同作用;大肠癌的发生机制涉及CyclinD1和p16调节环路中多个基因的异常。

hTERT mRNA与p16蛋白在非小细胞肺癌中的表达

背景与目的端粒酶逆转录酶(hTERT)和p16参与多种肿瘤的发生发展。本研究旨在探讨端粒酶逆转录酶和p16在人非小细胞肺癌组织中的表达情况。方法应用实时荧光定量RT-PCR法和免疫组化SP法检测117例非小细胞肺癌组织及癌旁组织,21例肺良性疾病组织中端粒酶逆转录酶和p16的表达情况。结果hTERT mRNA在非小细胞肺癌组织的表达量为2.937±0.836,明显高于正常肺组织2.042±0.378(t=-5.242,P<0.01);肺良性疾病中p16蛋白表达率为85.7%,高于癌组织中的47.9%,差异有统计学意义(P=0.004)。hTERT mRNA表达与非小细胞肺癌病理类型具有统计学意义(P<0.05),p16蛋白表达与非小细胞肺癌临床分期、淋巴结转移及细胞分化程度具有统计学意义(P<0.05)。hTERT mRNA与p16蛋白表达存在相关性(P<0.05)。结论hTERT mRNA表达对非小细胞肺癌诊断具有潜在临床价值,端粒酶逆转录酶和p16蛋白的表达情况与非小细胞肺癌的发生、发展有关。

挥发性有机化合物对p53、rasp21、p16表达影响

目的探讨苯、甲醛混合物对NIH/3T3细胞中p53、rasp21、p16表达的影响。方法采用免疫组化法（SABC）观察甲醛、苯混合物致NIH/3T3细胞p53、rasp21、p16的表达情况。结果经苯、甲醛混合物处理后的第9～15d,p53、rasp21、p16表达阳性率分别为26%～45%,50%～60%,阳性率远远高于阴性对照组,差异有统计学意义（P〈0.01）;p16的阳性率为64%～40%,阳性率低于阴性对照组,差异有统计学意义（P〈0.01）。结论（VOCs）可使突变型的p53蛋白表达率增高;上调ras癌基因家族的表达产物rasp21;下调肿瘤抑制基因p16的表达。这可能是VOCs致癌的原因之一。

P^(16)蛋白表达与胃癌的生物学行为

目的探讨P16蛋白与胃癌生物学行为的关系。方法采用免疫组化SP法检测33例胃癌、17例癌旁和13例正常胃粘膜中P16蛋白的表达。结果胃癌P16蛋白阳性表达率明显高于正常胃粘膜（P＜0．05）。癌旁与正常胃粘膜、胃癌阳性表达之间无显著性差异（P＞0．05）。伴淋巴结转移胃癌阳性细胞密度高于未转移者（P＜0．05）。P16蛋白表达与胃癌的其它生物学行为无统计学相关。结论P16基因异常有促进胃癌转移的效应，可作为胃癌预后的一个参考指标。