P16、P53和IMP3在宫颈癌前病变和宫颈癌中的表达和意义
发布时间：2018-08-08 14:35
【摘要】：目的： 1.研究P16,P53和IMP3的免疫组化表达与宫颈癌临床病理特征的关系,评价其对宫颈癌的诊断价值。 2.探讨P16或P53结合IMP3在检测宫颈癌前病变和宫颈癌中,保证敏感性的同时能否增加其特异性。 3.了解HPV感染和IMP3表达的关系。 方法： 该回顾性研究共收集120例病历,包括32例GIN Ⅰ,35例CINⅡ-Ⅲ和53例宫颈鳞癌(SCC)患者,此外还收集20例良性病历作为对照组。SCC组患者29例为FIGO分期Ⅰ期患者,Ⅱ期和Ⅲ期患者各12例,从切除子宫的宫颈组织、宫颈活检、宫颈锥切和LEEP手术中获取组织标本。使用福尔马林液浸泡固定宫颈组织,应用免疫组化法检测P16,P53和IMP3的表达。针对选取的病历选择的临床参数有：年龄、组织学诊断、FIGO分期、淋巴结转移、血管浸润和HC2结果。患者的年龄从24-63岁,平均年龄为42.7+7.964。SCC患者中最大年龄为61岁,最年轻的为27岁,平均年龄为44.6±7.8。CINⅡ-Ⅲ患者最大年龄为51岁,最年轻为25岁,平均年龄39.7±±6.8。CIN Ⅰ患者最大年龄为63岁,最年轻为24岁,平均年龄40.1±±9.2。良性病历组最大年龄为56岁,最年轻为41岁,平均年龄47.2±±3.443。使用SPSS19.0统计数据,所有数据统计均采用95%置信区间,5%的显著性水平。如P值0.05则考虑为有统计学差异。免疫染色为半定量法。使用Pearson检验方法评价P16, P53,IMP3在各研究组中的表达。使用相关系数来了解P16,P53和IMP3的超表达与多种临床参数的关系及各标记之间的关系。基于各标记物的共表达,计算其敏感性和特异性并绘制P16和IMP3共表达的ROC曲线。 结果： 1.在各研究组观察出P16,P53和IMP3的超表达不同,并具有统计学差异(P=0.003)。 2.检测P16存在于细胞浆和细胞核内,对照组未显示P16的超表达。研究组P16的表达具有差异性(P=0.024)。在不同FIGO分期患者中P16表达具有差异性(P=0.001)。P16的超表达与研究组密切相关。 3.除细胞核内均发现P53染色,对照组未显示P53的超表达。在研究组P53的表达具有差异性(P=0.007)。在SCC患者中,不同FIGO分期患者P53表达具有差异性。P53的超表达与研究组及FIG0分期密切相关(分别为ρ=0.275,P=0.002and p=0.358,P=0.008). 4.IMP3普遍存在于细胞浆中,在所有SCC患者中表现为高密度,而在CIN患者中为轻中密度。对照组未显示IMP3的表达。IMP3的超表达与宫颈病变的程度有关并具有统计学差异(P=0.000)。在SCC患者中,不同FIGO分期患者IMP3表达具有差异性(P=0.030)。IMP3的超表达与FIGO分期(ρ=0.292,P=0.036)、血管浸润(ρ=0.328,P=0.017)、阳性淋巴结(p=0.280,P=0.042)和HR-HPV感染(ρ=0.175,P=0.219)有关。 5.P16和IMP3在研究组中的表达呈正相关性,其相关性具有统计学差异(ρ=0.339,P=0.000)。 6.P16作为宫颈病变的独立检测因子其灵敏度和特异性分别为90%和50%。相似的PPV为75.2%,NPV为74.3%,阳性似然比为1.8,阴性似然比为0.2。 7.IMP3作为宫颈病变的独立检测因子其灵敏度和特异性分别为68.2%和92.3%。相似的PPV为93.7%,NPV为63.1%,阳性似然比为8.5,阴性似然比为0.35。 8.P16和IMP3的共表达在检测宫颈癌前病变和宫颈癌中,敏感性为87%,特异性为87.5%。相似地PPV为93.7%,NPV为75.7%,阳性似然比为6.69和阴性似然比为0.15.ROC曲线下面积为0.969。 结论： 1.P16表达与宫颈癌具有强相关性。在CIN患者中P16的表达未显示明显相关性。 2.P53表达与宫颈病变严重性呈正相关。大部分病历支持宫颈癌患者P53的免疫活性仅表现在少数细胞中,大部分野生型P53半衰期很短,因此很难检测其免疫组织化学性状。P53免疫活性可用来协助诊断肿瘤形成,但P53缺失并不能排除肿瘤的生成。 3.IMP3主要是在SCC患者中表达,与能预测肿瘤侵袭性的FIGO分期、淋巴结转移、血管浸润密切相关。因此IMP3被认为与肿瘤侵袭性相关。 4.IMP3表达与HR-HPV感染呈正相关。P16作为宫颈病变独立的检测因子具有较高的灵敏度但特异性较低,相反,IMP3具有较高的特异性,但灵敏度较低。而IMP3和P16共表达其灵敏度和特异性均明显提高,同时,其PPV和NPV较之其独立表达均明显提高。通过绘制并计算P16和IMP3的共表达ROC曲线下面积为0.969,可知对宫颈癌前病变及宫颈癌的评价效果与P16和IMP3的共表达的效果相当。
[Abstract]:Objective:
1. To study the relationship between the immunohistochemical expression of P16, P53 and IMP3 and the clinicopathological features of cervical cancer, and to evaluate the diagnostic value of P16, P53 and IMP3 in cervical cancer.
2. to explore whether P16 or P53 combined with IMP3 can enhance sensitivity in detecting cervical precancerous lesions and cervical cancer.
3. understand the relationship between HPV infection and IMP3 expression.
Method:
A total of 120 cases were collected in this retrospective study, including 32 cases of GIN I, 35 cases of CIN II - III and 53 cases of cervical squamous cell carcinoma (SCC). In addition, 20 cases of benign medical records were collected as FIGO stage I, 29 and 12 in group.SCC of the control group, and 12 cases in stage II and stage III, from the uterine cervix, cervix biopsy, cervix conization and LEEP operation. The tissue specimens were obtained. The cervical tissue was soaked with formalin solution and the expression of P16, P53 and IMP3 were detected by immunohistochemistry. The clinical parameters selected for the selected medical records were age, histological diagnosis, FIGO staging, lymph node metastasis, vascular infiltration and HC2 results. The age of the patients was 24-63 years old and the average age was 42.7+7.964.SCC The oldest age is 61 years, the youngest is 27 years old, the average age of 44.6 + 7.8.CIN II - III patients is 51 years old and the youngest is 25 years old. The average age of 39.7 + 6.8.CIN I patients is 63 years old and the youngest is 24 years old. The average age of 40.1 + 9.2. benign medical records is 56 years, the youngest is 41 years old, average age 47.2. + 3.443. using SPSS19.0 statistics, all data statistics use 95% confidence interval and 5% significant level. For example, P value 0.05 consider a statistical difference. Immune staining is a semi quantitative method. Pearson test method is used to evaluate the expression of P16, P53, IMP3 in each research group. The correlation coefficient is used to understand the overexpression of P16, P53 and IMP3. The relationship between various clinical parameters and the relationship between the various markers. Based on the co expression of the markers, the sensitivity and specificity were calculated and the ROC curves of the co expression of P16 and IMP3 were plotted.
Result:
1. the overexpression of P16, P53 and IMP3 in different study groups was different, and the difference was statistically significant (P=0.003).
2. P16 was detected in the cytoplasm and nucleus, and the control group did not show the overexpression of P16. The expression of P16 in the study group was different (P=0.024). In the patients with different FIGO stages, the expression of P16 was different (P=0.001).P16 overexpression was closely related to the study group.
3. the P53 staining was found in the nucleus except the nucleus, and the control group did not show the overexpression of P53. The expression of P53 in the study group was different (P=0.007). In the patients with SCC, the differential expression of.P53 in the P53 expression in the patients with different FIGO stages was closely related to the study group and the FIG0 staging (P =0.275, P=0.002and p=0.358, respectively).
4.IMP3 generally exists in the cytoplasm, high density in all SCC patients and light medium density in CIN patients. The control group does not show IMP3 expression of.IMP3, which is related to the degree of cervical lesions and has statistical difference (P=0.000). In SCC patients, the IMP3 expression in different FIGO staging patients has a difference (P=0.030).IMP3. Overexpression was associated with FIGO staging (p = 0.292, P = 0.036), vascular invasion (p = 0.328, P = 0.017), positive lymph nodes (p = 0.280, P = 0.042) and HR-HPV infection (p = 0.175, P = 0.219).
The expression of 5.P16 and IMP3 in the study group was positively correlated, and the correlation was statistically significant (P =0.339, P=0.000).
As an independent detection factor for cervical lesions, the sensitivity and specificity of 6.P16 were 90% and 50%., respectively, the PPV was 75.2%, NPV was 74.3%, the positive likelihood ratio was 1.8, and the negative likelihood ratio was 0.2..
As an independent detection factor for cervical lesions, the sensitivity and specificity of 7.IMP3 were 68.2% and 92.3%., respectively, the PPV was 93.7%, NPV was 63.1%, the positive likelihood ratio was 8.5, and the negative likelihood ratio was 0.35..
The co expression of 8.P16 and IMP3 was 87% in the detection of cervical precancerous lesions and cervical cancer. The specificity was 87.5%. similar to PPV 93.7%, NPV was 75.7%, the positive likelihood ratio was 6.69 and the negative likelihood ratio was 0.15.ROC curve 0.969..
Conclusion:
There was a strong correlation between 1.P16 expression and cervical cancer. The expression of P16 in CIN patients did not show significant correlation.
The expression of 2.P53 is positively correlated with the severity of cervical lesions. Most of the patients with cervical cancer support the immune activity of P53 only in a small number of cells, and most of the wild type P53 half-life is very short, so it is difficult to detect the immuno histochemical properties of the.P53 to help diagnose the formation of tumor, but the deletion of P53 can not exclude the tumor. Generate.
3.IMP3 is mainly expressed in SCC patients and is closely related to the FIGO staging, lymph node metastasis and vascular invasion that can predict tumor invasiveness. Therefore, IMP3 is considered to be associated with tumor invasiveness.
The expression of 4.IMP3 and HR-HPV infection was positively correlated with.P16 as the independent detection factor of cervical lesions with high sensitivity but low specificity. On the contrary, the sensitivity and sensitivity of IMP3 were higher, but IMP3 and P16 were both sensitivities and specificity increased obviously. In the same time, the independent expression of PPV and NPV was significantly higher than that of NPV. By drawing and calculating the coexpression of P16 and IMP3, the area of the co expression ROC curve is 0.969. It is known that the evaluation effect on cervical cancer precancerous and cervical cancer is equivalent to the co expression of P16 and IMP3.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.33
本文编号：2172095
[Abstract]:Objective:
1. To study the relationship between the immunohistochemical expression of P16, P53 and IMP3 and the clinicopathological features of cervical cancer, and to evaluate the diagnostic value of P16, P53 and IMP3 in cervical cancer.
2. to explore whether P16 or P53 combined with IMP3 can enhance sensitivity in detecting cervical precancerous lesions and cervical cancer.
3. understand the relationship between HPV infection and IMP3 expression.
Method:
A total of 120 cases were collected in this retrospective study, including 32 cases of GIN I, 35 cases of CIN II - III and 53 cases of cervical squamous cell carcinoma (SCC). In addition, 20 cases of benign medical records were collected as FIGO stage I, 29 and 12 in group.SCC of the control group, and 12 cases in stage II and stage III, from the uterine cervix, cervix biopsy, cervix conization and LEEP operation. The tissue specimens were obtained. The cervical tissue was soaked with formalin solution and the expression of P16, P53 and IMP3 were detected by immunohistochemistry. The clinical parameters selected for the selected medical records were age, histological diagnosis, FIGO staging, lymph node metastasis, vascular infiltration and HC2 results. The age of the patients was 24-63 years old and the average age was 42.7+7.964.SCC The oldest age is 61 years, the youngest is 27 years old, the average age of 44.6 + 7.8.CIN II - III patients is 51 years old and the youngest is 25 years old. The average age of 39.7 + 6.8.CIN I patients is 63 years old and the youngest is 24 years old. The average age of 40.1 + 9.2. benign medical records is 56 years, the youngest is 41 years old, average age 47.2. + 3.443. using SPSS19.0 statistics, all data statistics use 95% confidence interval and 5% significant level. For example, P value 0.05 consider a statistical difference. Immune staining is a semi quantitative method. Pearson test method is used to evaluate the expression of P16, P53, IMP3 in each research group. The correlation coefficient is used to understand the overexpression of P16, P53 and IMP3. The relationship between various clinical parameters and the relationship between the various markers. Based on the co expression of the markers, the sensitivity and specificity were calculated and the ROC curves of the co expression of P16 and IMP3 were plotted.
Result:
1. the overexpression of P16, P53 and IMP3 in different study groups was different, and the difference was statistically significant (P=0.003).
2. P16 was detected in the cytoplasm and nucleus, and the control group did not show the overexpression of P16. The expression of P16 in the study group was different (P=0.024). In the patients with different FIGO stages, the expression of P16 was different (P=0.001).P16 overexpression was closely related to the study group.
3. the P53 staining was found in the nucleus except the nucleus, and the control group did not show the overexpression of P53. The expression of P53 in the study group was different (P=0.007). In the patients with SCC, the differential expression of.P53 in the P53 expression in the patients with different FIGO stages was closely related to the study group and the FIG0 staging (P =0.275, P=0.002and p=0.358, respectively).
4.IMP3 generally exists in the cytoplasm, high density in all SCC patients and light medium density in CIN patients. The control group does not show IMP3 expression of.IMP3, which is related to the degree of cervical lesions and has statistical difference (P=0.000). In SCC patients, the IMP3 expression in different FIGO staging patients has a difference (P=0.030).IMP3. Overexpression was associated with FIGO staging (p = 0.292, P = 0.036), vascular invasion (p = 0.328, P = 0.017), positive lymph nodes (p = 0.280, P = 0.042) and HR-HPV infection (p = 0.175, P = 0.219).
The expression of 5.P16 and IMP3 in the study group was positively correlated, and the correlation was statistically significant (P =0.339, P=0.000).
As an independent detection factor for cervical lesions, the sensitivity and specificity of 6.P16 were 90% and 50%., respectively, the PPV was 75.2%, NPV was 74.3%, the positive likelihood ratio was 1.8, and the negative likelihood ratio was 0.2..
As an independent detection factor for cervical lesions, the sensitivity and specificity of 7.IMP3 were 68.2% and 92.3%., respectively, the PPV was 93.7%, NPV was 63.1%, the positive likelihood ratio was 8.5, and the negative likelihood ratio was 0.35..
The co expression of 8.P16 and IMP3 was 87% in the detection of cervical precancerous lesions and cervical cancer. The specificity was 87.5%. similar to PPV 93.7%, NPV was 75.7%, the positive likelihood ratio was 6.69 and the negative likelihood ratio was 0.15.ROC curve 0.969..
Conclusion:
There was a strong correlation between 1.P16 expression and cervical cancer. The expression of P16 in CIN patients did not show significant correlation.
The expression of 2.P53 is positively correlated with the severity of cervical lesions. Most of the patients with cervical cancer support the immune activity of P53 only in a small number of cells, and most of the wild type P53 half-life is very short, so it is difficult to detect the immuno histochemical properties of the.P53 to help diagnose the formation of tumor, but the deletion of P53 can not exclude the tumor. Generate.
3.IMP3 is mainly expressed in SCC patients and is closely related to the FIGO staging, lymph node metastasis and vascular invasion that can predict tumor invasiveness. Therefore, IMP3 is considered to be associated with tumor invasiveness.
The expression of 4.IMP3 and HR-HPV infection was positively correlated with.P16 as the independent detection factor of cervical lesions with high sensitivity but low specificity. On the contrary, the sensitivity and sensitivity of IMP3 were higher, but IMP3 and P16 were both sensitivities and specificity increased obviously. In the same time, the independent expression of PPV and NPV was significantly higher than that of NPV. By drawing and calculating the coexpression of P16 and IMP3, the area of the co expression ROC curve is 0.969. It is known that the evaluation effect on cervical cancer precancerous and cervical cancer is equivalent to the co expression of P16 and IMP3.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R737.33
【参考文献】
相关期刊论文 前1条
1 ;Quasi-likelihood estimation of average treatment effects based on model information[J];Science in China(Series A:Mathematics);2007年01期
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