P16/Ki-67双染联合DNA倍体分析在ASCUS分流诊断中的应用价值

目的： 探讨P16/Ki-67双染联合DNA倍体分析在宫颈意义不明的不典型鳞状细胞（ASCUS）分流诊断中的应用价值。方法： 选取2016年12月-2018年8月上海市长宁区妇幼保健院收治的经液基细胞学（LCT）诊断为ASCUS的患者115例，同时行P16/Ki-67双染检测，DNA倍体分析，且以阴道镜病理活检结果为金标准。结果： 115例患者阴道镜病理活检结果提示，宫颈上皮瘤变2级及以上（CIN2+）45例，其中CIN2级20例，CIN3级23例，鳞癌2例；P16/Ki-67双染检测CIN2+的灵敏性、特异性、诊断符合率分别为77.8%、77.1%、77.4%；DNA倍体分析检测CIN2+的灵敏性、特异性、诊断符合率分别为71.1%、34.3%、48.7%，且DNA倍体阴性的细胞标本中P16/Ki-67双染检测结果均为阴性；DNA倍体分析联合P16/Ki-67双染检测CIN2+的灵敏性、特异性、诊断符合率分别为92.9%、71.4%、86.3%，其中诊断符合率明显高于单纯采用DNA倍体分析（P < 0.05）。结论： P16/Ki-67双染相较于DNA倍体分析检测CIN2+具有更高灵敏度和特异度，两者联合检测能有效提高准确率，可辅助用于ASCUS的分流诊断。     

阴道镜联合p16/Ki-67双染对不典型鳞状细胞诊断的应用价值

[目的]探究阴道镜联合p16/Ki-67双染对不典型鳞状细胞(ASC-US)诊断中的应用价值。[方法]选取2016年1月到2019年1月410例经液基细胞学检测确诊为ASC-US患者,患者均行阴道镜和组织病理检查,取其细胞学样本进行p16/Ki-67双染检测。[结果]宫颈上皮瘤变2级及以上有(CIN2+)161例,其中2级72例,3级82例,鳞癌9例。阴道镜检测发现CIN2+的敏感度、特异性、诊断符合率分别为82.0%、64.3%和71.2%;p16/Ki-67双染检测发现CIN2+的敏感度、特异性、诊断符合率分别为77.6%、77.1%和68.9%;阴道镜检查、p16/Ki-67双染检测及联合诊断CIN2+的ROC曲线下面积分别为0.731、0.744和0.860。[结论]阴道镜联合p16/Ki-67双染检测具有较高的敏感度和特异性,准确率高于单一检测方法,能较准确分流ASC-US。     

Ki-67和DNA倍体分析与乳腺癌淋巴转移倾向

[目的]探讨乳腺癌组织的Ki鄄67基因表达和DNA倍体与其淋巴转移倾向的关系。[方法]采用流式细胞技术对72例乳腺癌组织新鲜标本进行Ki鄄67表达及肿瘤细胞DNA倍体含量检测的研究。[结果]Ki鄄67表达与乳腺癌病变大小、病理类型和ER无关。乳腺癌腋淋巴转移阳性组DNA异倍体高于无淋巴转移组(P<0.05)。Ki鄄67在腋淋巴转移阳性组高表达,其阳性表达百分比分别是:腋淋巴结转移组为12.61±6.23;无转移组为7.61±3.85(P<0.05)。[结论]Ki鄄67表达及DNA倍体可作为判断乳腺癌具有淋巴转移倾向的临床参考指标。     

Ki-67检测及DNA倍体分析与乳腺癌淋巴转移倾向的研究

目的探讨Ki-67基因在乳腺癌组织的表达及DNA倍体与其淋巴转移倾向的关系.方法采用流式细胞技术对72例乳腺癌组织新鲜标本进行Ki-67表达及肿瘤细胞DNA倍体含量检测的研究.结果Ki-67表达与乳腺癌肿瘤大小、病理类型和ER无关.乳腺癌腋淋巴转移阳性组DNA异倍体高于无淋巴转移组(P＜0.05),Ki+67在腋淋巴转移阳性组高表达.阳性组表达12.6l±6.23;阴性组表达7.6l±3.85(P＜0.05).结论Ki-67表达及DNA倍体可作为判断乳腺癌具有转移倾向的临床参考指标.肿瘤防治杂志,2001,8(特)240-242     

免疫细胞化学P16/Ki-67双染、P16 INK4α单染及高危型人乳头瘤病毒检测筛查高级别子宫颈病变价值比较

目的:探讨免疫细胞化学P16/Ki-67双染、P16 INK4α单染及高危型人乳头瘤病毒（HR-HPV）检测对高级别子宫颈病变的筛查价值。 方法:回顾性分析2019年3月至2021年7月于太原钢铁（集团）有限公司总医院同时行子宫颈薄层液基细胞学（TCT）及HR-HPV检测的622例患者临床资料,对...     

P16INK4a和Ki-67在宫颈癌前病变诊断中的意义

目的研究P16INK4a、Ki-67在宫颈癌前病变中的表达及早期诊断价值。方法宫颈活检标本92例,采用免疫组织化学PV-9000二步法检测宫颈鳞癌28例,CIN 45例（CINⅢ级17例、CINⅡ级7例、CINⅠ级21例）,炎性病变19例。结果在宫颈癌、CIN病变、宫颈炎P16INK4a的阳性表达率分别为100%、44.4%和10.5%,Ki-67的阳性表达率分别为100%、51.11%、21.05%,三组不同病变比较均差异有显著性（P〈0.001）。P16INK4a与Ki-67表达存在正相关（r2=0.893,P〈0.001）。结论 P16INk4a、Ki-67联合检测可以提高宫颈癌的早期诊断率。     

P16/Ki-67蛋白双染在未明确意义的非典型鳞状上皮细胞人群中分流作用

摘 要：［目的］探讨p16/Ki-67免疫细胞双染法对宫颈细胞学为未明确意义的非典型鳞状上皮细胞（ASCUS）人群的分流效果。［方法］ 以2016年4月至12月在郑州大学第二附属医院妇科门诊就诊且被诊断为ASCUS的135例妇女为研究对象,收集其宫颈脱落细胞标本,进行14种高危型HPV DNA及p16/Ki-67蛋白检测,所有妇女均进行阴道镜活检和病理学检查。以组织病理学诊断为金标准,分别计算p16/Ki-67双染、高危型HPV（HR-HPV）和HPV16/18检测的敏感性、特异性、阳性预测值（PPV）、阴性预测值（NPV）、转诊率及其95%CI。［结果］ 135例ASCUS妇女平均年龄为（46.48±10.19）岁（23~64岁）,其中诊断为宫颈上皮内瘤变（CIN）1级者7例,诊断为CIN2级及以上（CIN2+）者22例。随异常病理结果的严重性增加,p16/Ki-67双染、HR-HPV和HPV16/18检出阳性率均升高（P<0.001）。以CIN2+作为疾病终点指标时,p16/Ki-67双染对ASCUS人群分流的敏感性、特异性、PPV、NPV和转诊率分别为86.4%(95%CI：66.7%~95.3%)、85.8%(95%CI：78.2%~91.1%)、54.3%(95%CI：38.2%~69.5%)、97.0%(95%CI：91.6%~99.0%)和25.9%,与之相比,HR-HPV检测敏感性稍高［95.5%(95%CI：78.2%~ 99.2%)］,但特异性较低［68.1%(95%CI：59.1%~76.0%)］,转诊率较高（42.2%）,且差异均有统计学意义（P<0.05）。与p16/Ki-67双染法相比,HPV16/18的特异性较高［92.9%(95%CI：86.7%~96.4%)］,但敏感性很低［59.1%(95%CI：38.7%~76.7%)］。按照45岁进行年龄分层后,p16/Ki-67双染在≥45岁组ASCUS人群中分流效果要更好,敏感性为81.8%(95%CI：52.3%~94.9%),特异性为95.5%(95%CI：87.5%~98.4%)。［结论］ P16/Ki-67双染检测在保持高敏感性的同时,有更高的特异性,因此对ASCUS人群的分流效果优于HR-HPV和HPV16/18。P16/Ki-67双染检测具有简便、客观、高效、易于重复的特点,可为ASCUS人群提供一种新的分流方法。     

DNA倍体分析在恶性腹腔积液诊断中的价值

目的探讨DNA异倍体对于恶性腹腔积液的诊断价值。方法抽取64例中等量以上腹腔积液患者的腹水，分离其中的细胞，制备单细胞悬液，应用流式细胞仪分析DNA异倍体。结果DNA异倍体在肿瘤细胞中出现率（82．7％）显著高于非肿瘤细胞（0），统计学检验表明两者有显著性差异。结论流式细胞术分析腹水细胞的DNA异倍体，对于恶性肿瘤的细胞学诊断有较大的意义，可在临床推广应用。     

免疫细胞化学P16/Ki-67双染、P16INK4α单染及高危型人乳头瘤病毒检测筛查高级别子宫颈病变价值比较

目的探讨免疫细胞化学P16/Ki-67双染、P16INK4α单染及高危型人乳头瘤病毒(HR-HPV)检测对高级别子宫颈病变的筛查价值。方法回顾性分析2019年3月至2021年7月于太原钢铁(集团)有限公司总医院同时行子宫颈薄层液基细胞学(TCT)及HR-HPV检测的622例患者临床资料, 对患者剩余细胞学标本进行P16/Ki-67双染和P16INK4α单染检测。其中334例TCT结果提示为意义不明的非典型鳞状细胞(ASCUS)以上病变及HPV阳性患者行阴道镜病理活组织检查。以病理结果为参照, 比较P16/Ki-67双染、P16INK4α单染及HR-HPV检测筛查高级别鳞状上皮内瘤变(HSIL)及子宫颈癌的阳性预测值、灵敏度、特异度及准确度。结果以组织病理学结果为参照, 结合TCT检测结果, 622例患者中31例为HSIL, 其中P16/Ki-67双染阳性22例(71.0%), P16INK4α单染阳性23例(74.2%), HR-HPV检测阳性25例(80.6%);4例为子宫颈癌, 3种检测方法阳性率均为100.0%(4/4)。622例患者中, P16/Ki-67双染、P16INK4α...     

抑癌基因P16,P53在人肺癌中的表达及DNA倍体研究

目的 研究P16,P53基因在人肺癌中的表达和DNA倍体的关系及意义。方法 以SP免疫组化法检测肺癌组织中P16,P53表达,图像分析仪测定DNA倍体。结果 P16在肺痛表达阳性率为51.2％,低于癌旁组织(P<0.05),腺癌P16阳性率最高为68.8％,高于鳞癌及未分化癌(P<0.05),P53在肺癌表达阳性率为80.5％,明显高于癌旁组织(P<0.01),其中鳞癌阳性率高于其他组织类型(P<0.05),在有淋巴结转移和无淋巴结转移组间及Ⅰ、Ⅱ期与Ⅲ、Ⅳ期两组间,P16和P53表达阳性率均有显著差异(P<0.01)。同时发现二倍体P16阳性率,P53阴性率均显著高于异倍体(P<0.05)。结论 P16和P53基因异常与肺癌发生有关,且在不同类型肺癌发生中的作用不同,可作为判断肺癌生物学行为和预后的参考指标。     

P16/Ki-67 Dual Staining in Positive Human Papillomavirus DNA Testing for Predictive Diagnosis of Abnormal Cervical Lesions in Northeastern Thai Women

Objective: Cervical cancer screening can effectively reduce new cervical cancer cases, including in Thailand. The abnormal results are subsequently referred for colposcopy. To avoid unnecessary colposcopy, an efficient triage is still needed for validation. This study aimed to investigate the overall positivity of cytology-based screening, HPV detection, and p16/Ki-67 dual staining and evaluate different triage strategies for predictive diagnosis of abnormal cervical lesions in northeastern Thailand. Methods: Cervical cells were collected from 191 women who came for cervical screening in the gynecological outpatient department during March 2019-February 2020. Pap smear samples were classified into 6 groups including 17 atypical glandular cells (AGC), 21 atypical squamous cells of undetermined significance (ASC-US), 7 atypical squamous cells - cannot exclude HSIL (ASC-H), 26 low-grade squamous intraepithelial lesions (LSILs), 19 high-grade SILs (HSILs) and 101 no squamous intraepithelial lesion (noSIL). Polymerase chain reaction (PCR) was performed for HPV DNA detection. HPV genotyping was determined by reverse line blot hybridization. P16/Ki-67 dual staining was performed by using CINtec PLUS Cytology kit. Biopsies from abnormal screening were collected for surgical pathology classification. Results: High-risk HPV (HR-HPV) infection was 2.97%, 29.41%, 38.10%, 57.14%, 46.15% and 84.21% in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL cytology respectively. P16/ Ki-67 in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL was 0.99%, 5.88%, 9.52%, 42.86%, 26.92% and 63.16%, respectively (P-value < 0.001). Among p16/Ki-67 positive cases, 96.15% (25/26) were infected with HPV and 84.62% (22/26) were HR-HPV. The overall positivity of each and co-testing between cytology or HPV DNA testing or p16/Ki-67 dual staining was evaluated. In each cervical lesion, primary HPV DNA testing showed the highest sensitivity, but low specificity. The combined all HPV/HR-HPV with p16/Ki-67 detection increased the specificity of abnormal cervical lesions. Conclusion: P16/Ki-67 dual stain cytology in HPV-positive women performs well for diagnosis of abnormal cervical lesions and should be considered for management of HPV-positive women to avoid unnecessary colposcopy referrals.     

宫颈上皮内瘤样病变发生发展与p16/Ki-67共表达的相关性研究进展

宫颈上皮内瘤样病变（cervical intraepithelial neoplasia,CIN）属于宫颈癌前病变,虽然CIN进展成宫颈癌时间一般较长,但其发病率增多及发病年龄变小,对女性身心健康造成严重影响。随着宫颈癌筛查技术的进步和分子生物学技术的发展,高级别的宫颈癌上皮内瘤样变的早期检查确认并进行阻断已成为筛查的目标。p16被认为是发现最早的抑癌基因,在鉴别低级别与高级别宫颈鳞状上皮内病变中有重要作用。Ki-67为常见肿瘤标志物,在多种肿瘤中表达。p16/Ki-67双染为新型宫颈病变筛查或诊断方法,即同一细胞内检测到p16、Ki-67共表达,则提示细胞周期失调,考虑为宫颈上皮内高级别瘤样病变。国内近年有研究报道p16和Ki-67在CIN中的作用,未见到相关的综述报道。本文对宫颈上皮内瘤样病变与p16/Ki-67共表达的相关性作一综述,为临床宫颈病变鉴别、诊断提供参考。     

p16、Ki-67在宫颈鳞状上皮病变分级诊断中的意义

目的:探讨p16、Ki-67在宫颈鳞状上皮病变分级诊断中的意义.方法:收集我院2013年6月至2015年6月,阴道镜检查并宫颈活检病理127例,进行免疫组化p16、Ki-67检测,整理完整临床和病理资料作为研究对象.结果:根据127例宫颈活检HE染色及p16、Ki-67免疫组化结果修订原诊断.26例诊断为慢性宫颈炎;32例HSIL除1例考虑萎缩性改变,31例诊断HSIL;58例LSIL其中7例诊断为HSIL;1 1例CIN1-2中2例诊断为HSIL,9例诊断为LSIL;所有修订后HSIL,均随访1年.40例HSIL患者行Leep、宫颈锥切治疗,病理诊断除1例表现为p16、Ki-67阴性外(考虑萎缩性改变),与活检病理诊断一致.结论:联合免疫组化p16、Ki-67检测,在宫颈鳞状上皮病变分级诊断、治疗中具有重要意义,p16在肿瘤性病变中过表达更具特异性.     

Evaluation of P16/Ki67 (CINtecPlus) and L1-capsid compared with HPV-genotyping in cervical cytology in women ≥35 years old focusing on patients with atypical squamous cells of undetermined significance

Cervical cancer is the third most common cancer in women worldwide. Conventional cytological examination as a screening method with Papanicolaou has been established to reduce the incidence of dysplasia and cervical cancer for years. In addition to the conventional screening, the introduction of immunocytochemical examinations, including CINtecPlus and L1-capsid, has been demonstrated to have a positive impact on screening results. In addition to morphological screening methods, human papillomavirus (HPV)-testing has also been demonstrated to possess an enormous potential in the cervical screening process. Additionally, different screening models ranging from conventional cytological screening to primary HPV-testing do exist in different countries. At the beginning of the year 2020, a combination of cytological screening and HPV-testing was introduced in Germany for women ≥35 years. The aim of the present study was to evaluate the role of morphological screening, including immunocytochemistry, and to compare it with HPV-genotyping. Immunocytochemistry was added to confirm the diagnosis but needs established infrastructure and well-trained personnel. Furthermore, there was a need to establish the HPV-screening method. In the Institute for Pathology and Cytology (Schuettorf, Leer, Germany), 146,800 samples of women (>35 years old) were examined between January 2020 and January 2021. The present study retrospectively analyzed 146,800 samples. Each sample was examined using a conventional cytological technique and HPV-high risk-Test (HPV-HR-Test) with Viper-BD. Immunocytochemistry with CINtecPlus and L1-capsid was added in some cases. A total of 555 cases were cytological diagnosed as atypical squamous cells of undetermined significance (ASC-US; IIp). After performing immunocytochemistry, 79% of cases were suspected to be positive and 1.48% of cases were definitely positive. The HPV-HR-Test was positive in 26.4% of cases. Among cases of ASC-US and HPV-HR-negativity, 33.7% were suspicious of immunocytochemical positivity and 0.5% were definitely positive. Among patients with HPV-16-negativity, 13.6% were patients with highly squamous intraepithelial lesion (HSIL) and 22.7% were patients with low-grade squamous intraepithelial lesion (LSIL) and HSIL. Among patients with HPV-18-negativity, 14.3% were patients with HSIL and 19.5% were patients with LSIL and HSIL. There were 107 cases in this group of cases with negativity of both HPV-16 and HPV-18. After performing the colposcopy and biopsy, there were 6.5% with cervical intra-epithelial neoplasia (CIN) I, 8.4% with CIN II and 5.6% with CIN III. In conclusion, there is still a need for conventional cytological examination and maybe the addition of immunocytochemistry to confirm the diagnosis and to exclude dysplasia of cervical epithelium. The HPV-HR-Test is not enough as a screening method and may be misleading.     

食管鳞癌组织p16与Ki-67表达临床意义分析

目的:探讨食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)组织中p16与Ki-67表达,分析其与临床病理特征及预后相关性。方法:采用免疫组织化学SP法检测63例术后ESCC组织中p16与Ki-67表达,并分析与临床病理特征及预后的关系。表达程度与临床病理参数之间应用Spearman相关分析处理,应用Cox比例风险模型作预后因素分析。结果:ESCC组织中p16缺失率和Ki-67的阳性表达增高率分别为58.73%(37/63)和65.08%(41/63),p16缺失和Ki-67表达增高呈正相关,P=0.001。p16缺失及Ki-67阳性表达与临床分期(P值均<0.001)、淋巴转移(P值分别为0.010、0.008)呈正相关,而与肿瘤大小(P值分别为0.396和0.098)及组织学分级(P值分别为0.514和0.389)无关。Kap-lan-Meier生存分析结果显示,p16表达缺失率(P=0.004)及Ki-67的表达增高率(P=0.006)与生存时间缩短呈正相关。多因素Cox回归分析显示,p16(P=0.038)和Ki-67(P=0.044)表达、淋巴转移(P=0.021)、临床分期(P=0.031)和术后治疗(P=0.004)是影响患者预后的独立危险因素。结论:食管鳞状细胞癌组织中p16与Ki-67表达与临床分期、淋巴结转移和预后相关。p16与Ki-67检测有可能成为判断食管鳞状细胞癌分期和预后的重要分子标志,并成为重要的预后因素。     

P16INK4a及Ki-67免疫细胞化学检测对ASC-US中高级别病变检出的意义

目的：探讨液基细胞学剩余细胞标本P16INK4a、Ki-67免疫细胞化学染色检测宫颈癌前病变的价值。方法：选取2010年1月至2012年6月因宫颈疾病于北京大学第三医院妇产科就诊患者液基细胞学剩余标本50例。所有患者行高危型HPVDNA杂交捕获II代（HCII）检测,P16INK4a、Ki-67免疫细胞化学检测,同时行阴道镜检查及组织病理学活检。结果：以病理诊断将患者分为CIN2以下组和CIN2及以上组。CIN2及以上组P16INK4a及Ki-67表达量高于CIN2以下组,差异均具有统计学意义（P〈0．05）;P16INK4a或Ki-67检测对高级别病变预测的准确性在ASC—US组中优于异常细胞学组;在ASC—US中,P16INK4a或Ki-67检测对高级别病变预测的准确性优于高危型HPV检测。结论：宫颈脱落细胞中P16INK4a或Ki-67免疫细胞化学检测相比于高危型HPV检测可以提高对ASC—US中高级别病变的检出作用。