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.

温石棉对内皮细胞Wnt5a、p16和p21表达的影响

目的探讨温石棉对人脐静脉内皮细胞(HUVECs)的影响。方法实验组以50、100、200 mg/L温石棉纤维液刺激HUVECs 24、48、72 h,对照组仅加RPMI 1640培养基培养细胞,观察细胞形态变化,β-半乳糖苷酶法分析细胞衰老情况,四甲基偶氮唑蓝法检测细胞存活率。采用实时荧光定量PCR法检测细胞中Wnt5a、p16和p21 mRNA的表达情况。结果实验组HUVECs多呈梭形,部分呈圆形或不规则形,出现裸核及空泡现象,可见死亡细胞。随温石棉质量浓度及暴露时间的增加,细胞活性逐渐降低,衰老细胞逐渐增多。100 mg/L温石棉处理HUVECs 24 h时,细胞生长较活跃。与对照组相比,实验组Wnt5a、p16和p21 mRNA表达水平均增高(P<0.05)。结论温石棉可促进HUVECs衰老,Wnt5a、p16和p21参与此过程。

DNA倍体定量分析结合P16蛋白在宫颈癌筛查中的意义

目的:探讨DNA定量分析结合P16蛋白免疫组化染色在宫颈筛查中的意义。方法:选取2020年3月~2021年3月淮安市肿瘤医院门诊及住院检查病例4334例为研究对象,对宫颈细胞学DNA定量分析提示异常者,在知情同意情况下,进行阴道镜下宫颈活检、组织学病理检查及P16蛋白染色检查,比较分析DNA倍体定量分析提示异常者与其组织学病理之间的关系,以及P16蛋白表达与病理组织学之间的关系,以评价衡量DNA定量分析结合P16染色在宫颈癌筛查中的意义。结果:4334例中369例查出倍体异常,369例倍体异常中202例建议阴道镜活检,发现150例为CIN1级以上,同时对活检202例进行P16蛋白染色发现随着病变级别增高,P16表达百分比也随之上升,通过χ2检验发现P16蛋白在宫颈上皮内瘤变中表达有明显统计学意义(P<0.05)。结论:DNA倍体定量分析在宫颈癌筛查中有一定意义,同时结合P16蛋白免疫组化染色及宫颈活检,对发现早期宫颈病变有意义。

美洲大蠊提取物CⅡ-3调控p16^(INK4a)诱导SKOV3细胞衰老

目的探讨美洲大蠊提取物CⅡ-3调控p16^(INK4a)蛋白诱导卵巢癌细胞SKOV3衰老的作用。方法通过CCK-8法测定不同浓度和时间美洲大蠊提取物CⅡ-3对SKOV3细胞增殖的作用;运用细胞集落形成实验测定美洲大蠊提取物CⅡ-3对SKOV3细胞增殖能力的影响;流式细胞术检测CⅡ-3作用后SKOV3细胞周期的变化;衰老相关-β-半乳糖苷酶(SA-β-Gal)染色检测CⅡ-3作用后SKOV3细胞衰老变化;Western Blotting检测CⅡ-3作用后SKOV3细胞衰老调控分子p16^(INK4a)蛋白表达的变化。结果美洲大蠊提取物CⅡ-3可有效抑制SKOV3细胞增殖,最佳作用浓度为80μg/mL,作用时间为48 h;CⅡ-3作用后,SKOV3细胞集落形成能力下降;阻滞于G_(0)/G_(1)期细胞比例增高,S期细胞比例减少;SA-β-Gal阳性细胞百分比增加;衰老调控分子p16^(INK4a)蛋白表达上调。结论美洲大蠊提取物CⅡ-3通过调控衰老调控分子p16^(INK4a)蛋白表达诱导SKOV3细胞衰老。

P53、P16及Ki-67与早期食管癌患者ESD术后复发的关系分析

目的 分析研究抑制蛋白基因P53(P53)、抑制蛋白基因P16(P16)及细胞增殖核抗原Ki-67(Ki-67)与早期食管癌患者内镜黏膜下剥离术(ESD)术后复发的关系。方法 选取2019年1月至2023年1月三门峡市中心医院收治80例的早期食管癌患者作为研究对象,均进行ESD治疗。比较所有患者癌组织与癌旁组织(距肿瘤边缘>3 cm,镜下未见肿瘤组织或不典型增生组织)P53、P16、Ki-67蛋白表达。ESD术后对患者随访1年,根据有无术后复发食管癌,将患者分为复发组(n=20)与无复发组(n=60)。比较两组癌组织P53、P16、Ki-67蛋白表达。采用多因素Logistic回归分析早期食管癌患者ESD术后复发的影响因素,并绘制ROC曲线分析P53、P16、Ki-67蛋白表达与早期食管癌患者ESD术后复发。结果 与癌旁组织相比,癌组织P53、Ki-67蛋白表达升高,P16蛋白表达降低(t=9.276、13.987、10.595,均P<0.05);复发组的癌组织P53、Ki-67蛋白表达均高于无复发组,P16蛋白表达低于无复发组(t=5.086、4.648、5.139,均P<0.05);多因素Logistic回归分析显示,肿瘤低分化(OR=1.870)、肿瘤浸润侵犯黏膜下层(OR=1.808)、有淋巴结转移(OR=2.089)、P53蛋白高表达(OR=2.046)、P16蛋白低表达(OR=1.988)及Ki-67蛋白高表达(OR=1.761)均是早期食管癌患者ESD术后复发的独立危险因素(P<0.05);ROC曲线分析显示,P53、P16、Ki-67蛋白表达及联合检测的曲线下面积(AUC)分别为0.803、0.828、0.834、0.942,联合检测优于单一检测(P<0.05)。结论 P53、P16及Ki-67蛋白与早期食管癌患者ESD术后复发情况相关,可以作为辅助预测的相关诊断指标。

术前WLR及p16蛋白检测对阴茎癌患者生存情况的预测价值

目的评估术前白细胞与淋巴细胞比值(WLR)及p16蛋白表达检测对阴茎癌患者生存情况的预测价值。方法本研究为回顾性队列研究,选取2018年1月至2020年1月在咸阳市第一人民医院治疗的91例阴茎癌患者作为研究对象,所有患者均行阴茎部分切除术,术后对患者进行为期3年的随访,根据预后情况分为生存组(58例)和死亡组(33例)。生存组年龄(61.12±7.13)岁;死亡组年龄(60.88±7.22)岁。对比两组患者基线资料及术前影像学检查结果(肿瘤部位、肿瘤长径、神经侵犯、淋巴结转移、分化程度),测定血管内皮生长因子(VEGF)、肿瘤坏死因子受体相关蛋白1(TRAP1),并检测切除组织中p16蛋白表达情况,计算术前WLR、外周血中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、单核细胞与淋巴细胞比值(MLR)。通过logistic回归分析评估患者生存情况的影响因素,并利用受试者操作特征曲线(ROC)评估WLR联合p16蛋白表达对阴茎癌患者术后死亡的预测价值。统计学方法采用t检验、χ^(2)检验。结果两组患者基线资料及肿瘤部位、肿瘤长径、分化程度比较,差异均无统计学意义(均P>0.05)。死亡组神经侵犯、淋巴结转移及p16蛋白阳性表达占比均高于生存组[63.64%(21/33)比32.76%(19/58)、57.58%(19/33)比31.03%(18/58)、66.67%(22/33)比32.76%(19/58)],差异均有统计学意义(χ^(2)=8.140、6.141、9.769,均P<0.05)。死亡组患者术前WLR、NLR、PLR、MLR及VEGF、TRAPl水平均高于生存组[(5.62±0.91)比(4.11±0.75)、(5.27±0.88)比(3.91±0.71)、(181.06±25.13)比(145.32±20.64)、(0.58±0.20)比(0.32±0.12)、(539.03±52.48)ng/L比(442.18±47.36)ng/L、(58.01±6.63)ng/L比(45.25±5.82)ng/L],差异均有统计学意义(t=8.537、8.044、7.331、7.761、9.016、9.556,均P<0.05)。logistic回归分析显示,阴茎癌患者术前肿瘤神经侵犯和淋巴结转移情况,以及p16蛋白、VEGF、TRAPl、WLR、NLR、PLR、MLR均是影响其预后的重要因素(均P<0.05)。ROC显示,WLR联合p16蛋白表达对患者死亡的预测准确度为0.943(0.896~0.990)。结论术前检测WLR及p16蛋白表达有助于评估阴茎癌患者术后生存情况。

液基薄层细胞学检查联合人乳头状瘤病毒、P16蛋白免疫组化染色检测在宫颈癌筛查中的价值

目的分析液基薄层细胞学检查(TCT)联合人乳头状瘤病毒(HPV)、P16蛋白免疫组化染色检测在宫颈癌筛查中的价值。方法选取2021年7月至2023年5月于京山市人民医院接受宫颈癌筛查的180例女性,进行TCT、HPV、P16蛋白检测,以病理结果为金标准,分析不同检测方法的诊断效能。结果病理结果显示,180例中,阳性50例,阴性130例;TCT+HPV+P16检测的灵敏度、阳性预测值高于TCT+HPV检测、P16检测(P<0.05)。结论TCT联合HPV、P16蛋白检测在宫颈癌筛查中的价值较高,能提升灵敏度、阳性预测值。

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.

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.

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.

P16蛋白检测联合HR-HPV、TCT在宫颈癌前病变及宫颈癌诊断中的价值

目的:探讨P16蛋白检测联合高危型人乳头瘤病毒(high-risk human papilloma virus,HR-HPV)、液基薄层细胞学检测(thinprep cytologic test,TCT)在宫颈癌前病变及宫颈癌诊断中的临床价值。方法:选取2019年9月至2021年8月在承德市中心医院妇科门诊行宫颈癌筛查的390例患者为研究对象。所有患者均行P16蛋白、HRHPV及TCT检测。任一结果阳性者或高度怀疑宫颈恶性病变者行阴道镜下宫颈活检组织病理检查。探讨P16蛋白、HR-HPV、TCT检测及两两联合检测在宫颈癌中的诊断,并绘制诊断的受试者工作特征(receiver operating characteristic,ROC)曲线。结果:390例患者中,HR-HPV阳性者101例,阳性率25.90%(101/390);TCT阳性者64例,阳性率16.41%(64/390);P16阳性者57例,阳性率14.62%(57/390)。任一阳性者133例,共召回100例行阴道镜活检,组织病理学结果为:正常或炎症62例,宫颈低级别鳞状上皮内病变(low-grade squamous intraepithelial lesion,LSIL)19例,高级别鳞状上皮内病变(high-grade squamous intraepithelial lesion,HSIL)14例,宫颈癌5例;组织病理学检测阳性19例,阴性81例。在组织病理学检测阳性中,HR-HPV阳性18例,TCT检测阳性14例,P16阳性者17例。HR-HPV、TCT及P16诊断HSIL及宫颈癌的敏感度分别为94.74%、73.68%、89.47%,差异无统计学意义(P>0.05);P16诊断HSIL及宫颈癌的特异度高于TCT与HR-HPV检测,差异有统计学意义(P<0.05)。在两两联合检测中,HR-HPV+P16诊断HSIL及宫颈癌的敏感度最高,但3种联合检测方式的敏感度比较无统计学意义(P>0.05);TCT+P16诊断HSIL及宫颈癌的特异度为86.39%,高于HR-HPV+TCT、HR-HPV+P16(P<0.05)检测。HR-HPV、TCT、P16、HR-HPV+TCT、TCT+P16及HR-HPV+P16诊断宫颈癌前病变及宫颈癌的AUC分别为0.880、0.814、0.915、0.858、0.879、0.902。结论:P16的表达与宫颈病变进展具有正相关性,其可提高HSIL及宫颈癌的诊断效能,降低误诊率。P16+TCT检测相较于HR-HPV+TCT在不损失敏感度的前提下,有更高的特异度。

IDH突变型低级别星形细胞瘤p16蛋白表达与CDKN2A基因缺失状况的相关性

目的:以异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)突变型星形细胞瘤为研究对象,探讨利用p16蛋白免疫标记替代CDKN2A基因纯合性缺失检测的可行性。方法:收集我院既往组织学诊断为低级别星形细胞瘤(WHO 2级)且伴有IDH突变的胶质瘤42例,通过免疫组化方法检测肿瘤组织中p16蛋白表达,分别依据其胞核或胞浆阳性表达率将肿瘤分为阴性(阳性率0%)、低表达(0%<阳性率≤10%)、中表达(10%<阳性率≤25%)、高表达(25%<阳性率≤50%)及过表达(阳性率>50%)5个组别;利用FISH方法检测肿瘤CDKN2A基因纯合性缺失与杂合性缺失状况;采用Fisher精确检验评价p16蛋白表达水平与CDKN2A基因缺失间的相关性。结果:胞核p16蛋白表达水平与CDKN2A基因纯合性缺失间存在显著相关(P<0.001)。阴性组(4/4,100%)均检测到CDKN2A纯合性缺失,中、高及过表达组(22/22,100%)均未检测到CDKN2A纯合性缺失。低表达组与CDKN2A纯合性缺失间缺乏明确对应关系,其中3例(3/16,18.75%)检出纯合性缺失,13例(13/16,81.25%)未检出纯合性缺失。胞核p16蛋白表达水平与CDKN2A杂合性缺失无相关(P=0.228)。胞质p16蛋白表达水平与CDKN2A纯合性(P=0.086)或杂合性(P=0.884)缺失均无相关。结论:IDH突变且组织学呈低级别的星形细胞瘤中,胞核p16蛋白阴性(阳性率0%)或中等及以上表达(阳性率>10%)分别提示存在或不存在CDKN2A纯合性缺失。在上述区间p16蛋白与CDKN2A纯合性缺失间存在良好匹配关系,可用于协助病理诊断与分级。胞核p16蛋白低表达(0%<表达率≤10%)则不能预测CDKN2A纯合性缺失状态,此时仍需进行CDKN2A基因层面检测。

p16蛋白与HPV mRNA检测在口咽部鳞状细胞癌诊断中的意义

目的探讨p16蛋白与HPV mRNA检测在口咽部鳞状细胞癌(oropharyngeal squamous cell carcinoma,OPSCC)诊断中的意义。方法收集2019年11月~2021年10月首都医科大学附属北京同仁医院诊治的105例OPSCC,采用免疫组化EnVision两步法检测p16、Ki-67、p53蛋白表达,并检测其中61例HPV16/18 mRNA的表达,分析其与临床病理特征的关系。结果105例OPSCC中p16蛋白阳性58例(55.24%),阴性47例(44.76%);p16蛋白阳性患者比阴性患者的吸烟、饮酒史比例低(26/58 vs 37/47,16/58 vs 31/47),以扁桃体为常见发病部位(51/58 vs 18/47),易出现淋巴结转移(43/58 vs 23/47),Ki-67增殖指数较高(73.10%vs 47.45%),p53多为野生型(57/58 vs 16/47),形态学特征以非角化型鳞状细胞癌为主(29/58 vs 15/47),差异均有统计学意义(P<0.05)。61例HPV mRNA检测结果与p16蛋白表达完全一致(Kappa=1)。43例p16蛋白阳性OPSCC患者获得随访,3例复发/转移,1例肺转移后死亡;39例p16蛋白阴性OPSCC患者获得随访,8例复发/转移,7例死亡,其中2例为复发后死亡。结论HPV感染导致OPSCC发病率较高,以扁桃体为常见发病部位,p16蛋白表达与HPV mRNA表达具有较好的一致性,临床工作中可使用p16免疫组化检测代替HPV分子检测,进行HPV的感染筛查及辅助诊断。

液基脱落细胞学检查联合人乳头状瘤病毒、P16蛋白免疫组化染色检测在宫颈癌筛查中的价值分析

目的:分析液基脱落细胞学检查(thinprep cytologic test,TCT)联合人乳头状瘤病毒(human papilloma virus,HPV)、P16蛋白免疫组化染色检测在宫颈癌筛查中的价值。方法:选取2018年8月—2021年1月三明市中西医结合医院进行TCT和HPV检测的424例患者作为研究对象,将TCT和HPV任意一项检测阳性的138例患者进行P16蛋白免疫组化染色、阴道镜下宫颈组织活检。观察TCT、HPV及P16蛋白单项及联合诊断结果,计算各指标单项及联合诊断敏感度、特异度及准确度。结果:138例患者中病理诊断结果慢性炎症、CINⅠ、CINⅡ、CINⅢ、SCC分别为63例、42例、23例、9例、1例;TCT诊断敏感度、特异度、准确度分别为76.00%(57/75)、57.14%(36/63)、67.39%(93/138);HPV诊断阴性、阳性分别为53例、85例;HPV诊断敏感度、特异度、准确度分别为77.33%(58/75)、57.14%(36/63)、68.12%(94/138);P16蛋白诊断阴性、阳性分别为69例、69例,P16蛋白诊断敏感度、特异度、准确度分别为66.67%(50/75)、69.84%(44/63)、68.12%(94/138);TCT联合HPV、P16蛋白诊断敏感度、特异度、准确度分别为90.67%(68/75)、87.30%(55/63)、89.13%(123/138);TCT联合HPV、P16蛋白诊断敏感度、特异度、准确度均高于各单项指标诊断结果,差异有统计学意义(P<0.05)。结论:TCT联合HPV、P16蛋白免疫组化染色检测是筛查宫颈癌较为准确的方法,能够提高宫颈癌检出率,对患者是否需要行阴道镜下活检具有指导意义。

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.

P16/Ki-67双染联合密封蛋白4检测对宫颈高级别上皮内瘤变的诊断效能分析

目的探讨P16/Ki-67双染联合密封蛋白4(CLDN4)检测对宫颈高级别上皮内瘤变的诊断价值。方法回顾性分析2020年8月—2021年3月在华中科技大学同济医学院附属武汉儿童医院就诊并经宫颈切片病理诊断为低级别上皮内瘤变、高级别上皮内瘤变及慢性宫颈炎患者各32例,所有患者均行阴道镜直视下活检,且所有宫颈阻止标本均经P16/Ki-67双染和CLDN4检测。比较P16/Ki-67双染诊断结果与病理检查诊断结果;比较CLDN4诊断结果与病理检查诊断结果;比较P16/Ki-67双染、CLDN4联合诊断结果与病理检查诊断结果。绘制受试者工作特征(ROC)曲线评价P16/Ki-67双染联合CLDN4检测对宫颈高级别上皮内瘤变的诊断效能。结果P16/Ki67双染用于诊断宫颈高级别上皮内瘤变,有27例阳性患者与病理检查诊断结果一致,52例阴性患者与病理活检诊断结果一致,经一致性检验,两种诊断方法的一致性一般(κ=0.622,P=0.000);CLDN4用于诊断宫颈高级别上皮内瘤变,有25例阳性患者与病理检查诊断结果一致,51例阴性患者与病理检查诊断结果一致,经一致性检验,两种诊断方法的一致性一般(κ=0.552,P=0.000);P16/Ki-67双染、CLDN4联合诊断宫颈高级别上皮内瘤变,有30例阳性患者与病理检查诊断结果一致,62例阴性患者与病理检查诊断结果一致,经一致性检验,两种诊断方法的一致性较好(κ=0.906,P=0.000)。ROC曲线分析结果显示,P16/Ki-67双染、CLDN4及两者联合对宫颈高级别上皮内瘤变诊断的敏感性分别为84.38%(95%CI:0.665,0.941)、78.13%(95%CI:0.596,0.901)、93.75%(95%CI:0.778,0.989),特异性分别为81.25%(95%CI:0.692,0.895)、79.69%(95%CI:0.674,0.883)、96.88%(95%CI:0.882,0.995),曲线下面积分别为0.828(95%CI:0.738,0.897)、0.789(95%CI:0.694,0.866)、0.953(95%CI:0.890,0.986)。结论P16/Ki-67双染联合CLDN4检测对宫颈高级别上皮内瘤变的诊断效能较高。

蛋白激酶CK2β、P16蛋白、人乳头瘤病毒壳蛋白联合检测诊断宫颈癌的临床价值分析

目的:探讨宫颈癌患者采用蛋白激酶CK2β、P16蛋白、人乳头瘤病毒壳蛋白(HPVL-1)联合检测的临床诊断价值。方法:选取2020年6月—2022年1月单县中心医院收治的116例宫颈癌患者作为观察组,选取同时期收治的116例宫颈瘤变患者作为对照组。患者均接受病理、蛋白激酶CK2β、P16蛋白、HPVL-1检查,将临床综合检查结果作为金标准,分析蛋白激酶CK2β、P16蛋白、HPVL-1联合检测诊断宫颈癌的价值。结果:观察组HPVL-1阳性率低于对照组,P16、蛋白激酶CK2β阳性率高于对照组,差异有统计学意义(P<0.05)。HPVL-1、P16、蛋白激酶CK2β联合检测的灵敏度高于单一检测,漏诊率低于单一检测,差异有统计学意义(P<0.05)。结论:蛋白激酶CK2β、P16蛋白、HPVL-1联合检测诊断宫颈癌,灵敏度高,漏诊率低。

HLA-E、HLA-G及P16蛋白与宫颈癌患者高危型HPV感染的相关性

目的研究人类白细胞抗原(HLA)-E、HLA-G及P16蛋白与宫颈癌患者高危型人乳头瘤病毒(HR-HPV)感染的相关性。方法前瞻性选择2019年1月至2022年11月于湖北民族大学附属民大医院接受治疗的宫颈癌患者82例纳入宫颈癌组,选择同期于本院接受治疗的宫颈上皮内瘤变(CIN)患者64例为CIN组,选择同期于本院健康体检的正常女性60名纳入对照组。3组均行血清HLA-E、HLA-G水平、P16蛋白及HPV分型检测。观察3组HR-HPV分布、血清HLA-E、HLA-G水平及P16蛋白表达情况;观察不同CIN分级患者血清HLA-E、HLA-G水平及P16蛋白表达情况;观察HR-HPV感染宫颈癌不同病理特征患者血清HLA-G、HLA-E及P16蛋白表达情况;分析HLA-E、HLA-G及P16蛋白与HR-HPV感染宫颈癌患者HPV的相关性。结果宫颈癌组HR-HPV检出率大于CIN组、对照组,CIN组HR-HPV检出率大于对照组,差异均有统计学意义(P<0.05)。宫颈癌组ⅡA期患者HR-HPV感染率高于CIN组Ⅰ级、Ⅱ级、Ⅲ级及对照组患者,宫颈癌组IB期患者HR-HPV感染率高于CIN组Ⅰ级、Ⅱ级及对照组患者,CIN组Ⅲ级、Ⅱ级患者HR-HPV感染率高于CIN组Ⅰ级及对照组患者,差异均有统计学意义(P<0.05)。宫颈癌组血清HLA-E、HLA-G水平及P16蛋白阳性表达率均高于CIN组、对照组,CIN组血清HLA-E、HLA-G水平及P16蛋白阳性表达率均高于对照组,差异均有统计学意义(P<0.05)。CINⅡ级、CINⅢ级患者血清HLA-E、HLA-G水平及P16蛋白阳性表达率均高于CINⅠ级患者,CINⅢ级患者血清HLA-E、HLA-G水平及P16蛋白阳性表达率均高于CINⅡ级患者,差异均有统计学意义(P<0.05)。HR-HPV感染宫颈癌不同年龄、病理类型及是否绝经患者血清HLA-G、HLA-E水平及P16蛋白阳性率比较,差异均无统计学意义(P>0.05);不同FIGO分期、分化程度、HPV阳性分级患者血清HLA-G、HLA-E水平及P16蛋白阳性率比较,差异均有统计学意义(P<0.05)。经Pearson相关分析,血清HLA-G、HLA-E水平及P16蛋白与宫颈癌患者HR-HPV感染呈正相关(P<0.05)。结论高危型HPV持续感染是导致宫颈良性病变并进展为宫颈癌的重要因素。血清HLA-E、HLA-G水平升高及P16蛋白高表达是宫颈癌患者的重要特征。血清HLA-G、HLA-E水平及P16蛋白与宫颈癌患者HR-HPV感染正相关。

CK10、p16蛋白在早期宫颈癌组织中的表达及其与预后的关系

目的 分析CK10、p16蛋白在早期宫颈癌组织中的表达及其与预后关系,以期能为后期临床治疗提供指导。方法 选取首都医科大学附属北京佑安医院2015年1月至2017年1月采集的宫颈石蜡标本共200例,其中正常宫颈组织50例(A组),低级宫颈鳞状上皮内病变50例(B组),高级宫颈鳞状上皮50例(C组),早期宫颈癌50例(D组)。采用免疫组化方法检测并比较各组CK10、p16蛋白的阳性表达,分析CK10、p16蛋白表达对早期宫颈癌患者临床特征及预后的影响。结果 CK10蛋白在A、B、C、D组的阳性率分别为80.00%、66.00%、34.00%和22.00%,在早期宫颈癌中的阳性表达率最低,其次是宫颈病变,且随着病情的加重而降低。p16蛋白在A、B、C、D组的阳性率分别为10.00%、36.00%、64.00%和90.00%,在早期宫颈癌中阳性率最高,其次为宫颈病变,且随着病情的加重而增高;肿瘤中高分化、无淋巴结转移、浅层浸润间质的早期宫颈癌患者CK10蛋白阳性率较高差异有统计学意义(Z=5.279、4.781、5.383,P<0.05);肿瘤低分化、有淋巴结转移的早期宫颈癌患者p16蛋白阳性率较高(Z=4.236、5.078,P<0.05);随访5年内,CK10蛋白阴性表达患者2例因肿瘤复发死亡,阳性表达无一例死亡;p16蛋白阴性表达患者无一例死亡,阳性表达2例因肿瘤复发或转移死亡。CK10蛋白阳性表达及p16蛋白阴性表达患者的预后较佳。结论 CK10、p16的表达水平与宫颈病变程度呈负相关或正相关,肿瘤中高分化、无淋巴结转移、浅层浸润间质的早期宫颈癌患者CK10蛋白阳性率较高,预后较佳;肿瘤低分化、有淋巴结转移的早期宫颈癌患者p16蛋白阳性率较高,预后较差。

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.