目的 探讨Ki-67、微小染色体维持蛋白2（MCM2）、p16在宫颈鳞状上皮内病变中的表达及其临床意义。方法 采用免疫组化检测Ki-67、MCM2、p16在宫颈炎症组14例、低级别鳞状上皮内病变（LSIL）组47例、高级别鳞状上皮内病变（HSIL）组49例中的表达情况,以病理结果作为金标准,对结果进行统计分析。结果 HSIL组中Ki-67、MCM2、p16阳性率均高于炎症组和LSIL组（均P<0.017）。HSIL组中Ki-67、MCM2过表达率均显著高于炎症组和LSIL组（均P<0.017）。随着宫颈病变级别增加,Ki-67及MCM2阳性范围从基底层至表层逐渐扩大。MCM2及Ki-67在LSIL组中表达模式多为基底层的非过表达模式,HSIL组多为中层及以上的过表达模式。Spearman相关性分析显示,MCM2和Ki-67在宫颈鳞状上皮内病变中的表达强度之间呈正相关（r=0.801,P<0.05）;p16与MCM2在宫颈鳞状上皮内病变中的表达呈正相关（r=0.559,P<0.05）;p16与Ki-67在宫颈鳞状上皮内病变中的表达呈正相关（r=0.478,P<0.05）。结论 p16阳性提示宫颈高级别鳞状上皮内病变。MCM2与Ki-67在宫颈鳞状上皮内病变中的表达具有较高一致性,MCM2可作为宫颈鳞状上皮内病变新的增殖标志物。

Objective To investigate the expression and significance of Ki-67,MCM2 and p16 in cervical intraepithelial lesions．Methods The expressions of Ki-67,MCM2 and p16 in cervicitis group（14 cases）,low-grade squamous intraepithelial lesion（LSIL） group（47 cases）and high-grade squamous intraepithelial lesion（HSIL） group（49 cases）were detected by immunohistochemistry．The pathological results were used as the gold standard for statistical analysis．Results The positive rates of Ki-67,MCM2 and p16 in HSIL group were significantly higher than those in cervicitis group and LSIL group（P<0.017）．The over-expression rates of Ki-67,MCM2 in HSIL group were significantly higher than those in cervicitis group and LSIL group（P<0.017）．With the increase of cervical lesion grade,the positive range of Ki-67 and MCM2 gradually expanded from basal layer to surface layer．The expression patterns of MCM2 and Ki-67 in LSIL group were mostly non-overexpressed in the basal layers,while those in HSIL group were mostly overexpressed in the middle layer and above．Spearman correlation analysis showed that the expression intensity of MCM2 and Ki-67 in cervical squamous intraepithelial lesions was positively correlated（r=0.801,P<0.05）．There was a positive correlation between the expression of p16 and MCM2 in cervical squamous intraepithelial lesions（r=0.559,P<0.05）．There was a positive correlation between the expression of p16 and Ki-67 in cervical squamous intraepithelial lesions（r=0.478,P<0.05）．Conclusions Positive p16 indicates high-grade squamous intraepithelial lesion．The expression of MCM2 and Ki-67 in cervical intraepithelial lesions is highly consistent．MCM2 can be used as a new proliferative marker for cervical intraepithelial lesions．

目的 探讨p16/Ki-67染色、HPV E6/E7mRNA和联合检测对HSIL+病变诊断的临床价值。方法 募集2017年3月—2020年8月期间,于中山市博爱医院妇产科就诊,组织学证实为宫颈炎患者209例、LSIL患者169例、HSIL患者131例和宫颈癌患者86例作为研究对象,回顾分析研究对象术前细胞学样本p16/Ki-67染色、HPV E6/E7mRNA检测结果,纵向比较p16/Ki-67染色、HPV E6/E7mRNA和联合检测在不同级别宫颈病变的阳性率的差异,横向比较p16/Ki-67染色、HPV E6/E7mRNA和联合检测在相同宫颈病变的阳性率的差异,综合评估p16/Ki-67染色、HPV E6/E7mRNA和联合检测诊断HSIL+病变效能的差异。结果 ①纵向比较:p16/Ki-67染色、HPV E6/E7mRNA和联合检测阳性率随宫颈病变程度的加重呈趋势性升高(p16/Ki-67染色:χ²=374.34,P<0.001;HPV E6/E7mRNA检测:χ²=289.21,P<0.001;联合检测:χ²=343.90,P<0.001)。②横向比较:在宫颈炎、LSIL、宫颈癌组,p16/Ki-67染色、HPV E6/E7mRNA和联合检测阳性率之间差异均不具有统计学意义(均P>0.05)。在HSIL组,p16/Ki-67染色和联合检测之间阳性率差异有统计学意义(χ²=8.09,P=0.004); HPV E6/E7mRNA和联合检测之间阳性率差异有统计学意义(χ²=11.30,P=0.001)。③p16/Ki-67染色、HPV E6/E7mRNA和联合检测诊断HSIL+的灵敏度,总体差异有统计学意义(χ²=7.69,P=0.021)。p16/Ki-67染色与联合检测法之间的灵敏度差异有统计学意义(χ²=7.29,P=0.007);HPV E6/E7mRNA检测与联合检测法之间的灵敏度差异有统计学意义(χ²=4.84,P=0.028)。p16/Ki-67染色、HPV E6/E7mRNA和联合检测诊断HSIL+的特异度及符合率的总体差异不具有统计学意义(χ²₁=5.38,P₁=0.068;χ²₂=0.93,P₂=0.628)。结论 p16/Ki-67染色、HPV E6/E7mRNA 和联合检测均可有效筛出HSIL+病变,但是联合检测能显著提高HSIL+病变诊断的灵敏度,降低漏诊率,同时保持了较好的特异度和符合率,建议将p16/Ki-67染色和HPV E6/E7mRNA联合检测作为早期诊断HSIL+病变的策略。

Objective To investigate the clinical value of p16/Ki-67 staining E6/E7 mRNA and combined detection in the diagnosis of HSIL+ lesions. Methods From March 2017 to August 2020,209 cases of cervicitis,169 cases of LSIL,131 cases of HSIL and 86 cases of cervical cancer confirmed by histology were selected as the research objects. The results of p16/Ki-67 staining and HPV E6/E7 RNA detection of the preoperative cytological samples were retrospectively analyzed and the p16/Ki-67 staining and HPV E6/E7 mRNA detection results were compared longitudinally. The positive rates of E6/E7mRNA and combined detection in different grades of cervical lesions were compared.The positive rates of p16/Ki-67 staining,HPV E6/E7 mRNA and combined detection in the same cervical lesions were compared horizontally.The differences in the diagnostic efficacy of p16/Ki-67 staining,HPV E6/E7 mRNA and combined detection in the diagnosis of HSIL+lesions were comprehensively evaluated. Results ①Longitudinal comparison:the positive rates of p16/ Ki-67 staining, HPV E6/E7mRNA and combined detection increased with the severity of cervical lesions(p16/Ki-67 staining:χ²=374.34,P<0.001;HPV E6/E7 mRNA detection:χ²=289.21,P<0.001;joint detection:χ²=343.90,P<0.001). ②Transverse comparison: in cervicitis, LSIL and cervical cancer groups,there were no significant differences in the positive rates of p16/Ki-67 staining, HPV E6/E7 mRNA and combined detection (all P>0.05). In the HSIL group,there was significant difference in the positive rate between p16/Ki-67 staining and combined detection (χ²=8.09,P=0.004)and the difference between HPV E6/ E7 mRNA and combined detection was statistically significant(χ²=11.30,P=0.001). ③The sensitivity of p16/Ki-67staining,HPV E6/E7 mRNA and combined detection in the diagnosis of HSIL+ was statistically significant(χ²=7.69,P=0.021). The sensitivity difference between p16/Ki-67 staining and combined detection was statistically significant(χ²=7.29,P=0.007);the sensitivity difference between HPV E6/E7 mRNA detection and combined detection method was statistically significant (χ²=4.84,P=0.028). There was no significant difference in the specificity and coincidence rate of p16/Ki-67 staining,HPV E6/E7 mRNA and combined detection in the diagnosis of HSIL+(χ²₁=5.38,P₁=0.068;χ²₂=0.93,P₂=0.628). Conclusion P16/Ki-67 staining,HPV E6/E7 mRNA and combined detection may effectively screen out HSIL+ lesions,reduce the missed diagnosis rate, but the combined detection may significantly improve the sensitivity of diagnosis of HSIL+ lesions, while maintaining good specificity and coincidence rate.It is suggested that p16/Ki-67 staining and HPV E6/E7 mRNA detection should be used as a strategy for early diagnosis of HSIL+ lesions.

目的 观察比较术中及术前化疗干预对进展期胃恶性肿瘤手术患者p53、ki-67表达及预后的影响,为临床化疗时间的选择提供理论依据。方法 自2014年8月—2015年5月,我院共收入胃恶性肿瘤患者40例,将40例患者随机分为两组,每组各20例,保证两组患者在性别、年龄、胃癌分期等方面可比,无统计学差异(P＞0.05),标记为Ⅰ组和Ⅱ组。Ⅰ组20例患者于术前进行化疗干预,Ⅱ组在术中给予化疗干预。观察比较两组患者p53、ki-67表达状况及预后。结果 Ⅰ组及Ⅱ组治疗后p53及ki-67均比治疗前升高,差异有统计学意义(P<0.05)。但是治疗后,Ⅰ组和Ⅱ组的p53表达状况组间差异不明显,无统计学意义(P>0.05)。治疗前后,AI差异有统计学意义(P<0.05)。Ⅰ组效果明显好于Ⅱ组,两者差异有统计学意义(P <0.05)。术后六个月、一年随访时发现两组复发率、死亡率差别不大,无统计学意义(P>0.05),术后两年随访发现Ⅱ组复发率、死亡率明显低于Ⅰ组,差异有统计学意义(P<0.05)。结论 术中化疗的疗效优于术前化疗,患者预后较术前化疗好。

Objective To observe the effect of intraoperative and preoperative chemotherapy on the expression of p53, Ki-67 and prognosis in patients with advanced gastric cancer. Methods 40 cases of advanced gastric cancer in our hospital from Aug 2014 to May 2015 were enrolled in the study, and were divide into 2 groups randomly. In group I, 20 patients received chemotherapy intervention befoerer operation, and the other group received chemotherapy intervention during operation. The expressions and prognosis of p53 and Ki-67 were observed and compared between the two groups. Results Group Ⅰ and group Ⅱ after treatment, p53 and Ki-67 were higher than that before treatment, with statistical significance(P<0.05). However, there was no significant difference in the expression of p53 between group Ⅰ and group Ⅱ after treatment, and there was no significant difference(P>0.05). Before and after treatment, the difference of AI was significant, with statistical significance (P<0.05). The effect of group Ⅰ was obviously better than that of group Ⅱ, the difference was statistically significant(P<0.05). Six monthse after the operation and one year follow-up found two groups of recurrence rate and mortality rate had no significant difference(P>0.05). After two years follow-up found the group Ⅱ recurrence rate, mortality was lower than in group Ⅰ (P<0.05). Conclusion The effect of intraoperative chemotherapy is better than that of preoperative chemotherapy, and the prognosis is better than that of preoperative chemotherapy.

       目的   探讨Ki-67、微小染色体维持蛋白2（MCM2）、p16在宫颈鳞状上皮内病变中的表达及其临床意义。方法   采用免疫组化检测Ki-67、MCM2、p16在宫颈炎症组14例、低级别鳞状上皮内病变（LSIL）组47例、高级别鳞状上皮内病变（HSIL）组49例中的表达情况，以病理结果作为金标准，对结果进行统计分析。结果  HSIL组中Ki-67、MCM2、p16阳性率均高于炎症组和LSIL组（均P＜0.017）。HSIL组中Ki-67、MCM2过表达率均显著高于炎症组和LSIL组（均P＜0.017）。随着宫颈病变级别增加，Ki-67及MCM2阳性范围从基底层至表层逐渐扩大。MCM2及Ki-67在LSIL组中表达模式多为基底层的非过表达模式，HSIL组多为中层及以上的过表达模式。Spearman相关性分析显示，MCM2和Ki-67在宫颈鳞状上皮内病变中的表达强度之间呈正相关（r=0.801，P＜0.05）；p16与MCM2在宫颈鳞状上皮内病变中的表达呈正相关（r=0.559，P＜0.05）；p16与Ki-67在宫颈鳞状上皮内病变中的表达呈正相关（r=0.478，P＜0.05）。结论  p16阳性提示宫颈高级别鳞状上皮内病变。MCM2与Ki-67在宫颈鳞状上皮内病变中的表达具有较高一致性，MCM2可作为宫颈鳞状上皮内病变新的增殖标志物。

       Objective  To investigate the expression and significance of Ki-67，MCM2 and p16 in cervical intraepithelial lesions．Methods  The expressions of Ki-67，MCM2 and p16 in cervicitis group（14 cases），low-grade squamous intraepithelial lesion（LSIL） group（47 cases）and high-grade squamous intraepithelial lesion（HSIL） group（49 cases）were detected by immunohistochemistry．The pathological results were used as the gold standard for statistical analysis．Results  The positive  rates of Ki-67，MCM2 and p16 in HSIL group were significantly higher than those in cervicitis group and LSIL group（P＜0.017）．The over-expression rates of Ki-67，MCM2 in HSIL group were significantly higher than those in cervicitis group and LSIL grou（P＜0.017）．With the increase of cervical lesion grade，the positive range of Ki-67 and MCM2 gradually expanded from basallayer to surface layer．The expression patterns of MCM2 and Ki-67 in LSIL group were mostly non-overexpressed in the basal layers，while those in HSIL group were mostly overexpressed in the middle layer and above．Spearman correlation analysis showed that the expression intensity of MCM2 and Ki-67 in cervical squamous intraepithelial lesions was positively correlated（r=0.801，P＜0.05）．There was a positive correlation between the expression of p16 and MCM2 in cervical squamous intraepithelial lesions（r=0.559，P＜0.05）．There was a positive correlation between the expression of p16 and Ki-67 in cervical squamous intraepithelial lesions（r=0.478，P＜0.05）．Conclusions  Positive p16 indicates high-grade squamous intraepithelial lesion．The expression of MCM2 and Ki-67 in cervical intraepithelial lesions is highly consistent．MCM2 can be used as a new proliferative marker for cervical intraepithelial lesions．