P16、P53和IMP3在宮頸癌前病變和宮頸癌中的表達(dá)和意義
發(fā)布時間：2018-08-08 14:35
【摘要】：目的： 1.研究P16,P53和IMP3的免疫組化表達(dá)與宮頸癌臨床病理特征的關(guān)系,評價其對宮頸癌的診斷價值。 2.探討P16或P53結(jié)合IMP3在檢測宮頸癌前病變和宮頸癌中,保證敏感性的同時能否增加其特異性。 3.了解HPV感染和IMP3表達(dá)的關(guān)系。 方法： 該回顧性研究共收集120例病歷,包括32例GIN Ⅰ,35例CINⅡ-Ⅲ和53例宮頸鱗癌(SCC)患者,此外還收集20例良性病歷作為對照組。SCC組患者29例為FIGO分期Ⅰ期患者,Ⅱ期和Ⅲ期患者各12例,從切除子宮的宮頸組織、宮頸活檢、宮頸錐切和LEEP手術(shù)中獲取組織標(biāo)本。使用福爾馬林液浸泡固定宮頸組織,應(yīng)用免疫組化法檢測P16,P53和IMP3的表達(dá)。針對選取的病歷選擇的臨床參數(shù)有：年齡、組織學(xué)診斷、FIGO分期、淋巴結(jié)轉(zhuǎn)移、血管浸潤和HC2結(jié)果�；颊叩哪挲g從24-63歲,平均年齡為42.7+7.964。SCC患者中最大年齡為61歲,最年輕的為27歲,平均年齡為44.6±7.8。CINⅡ-Ⅲ患者最大年齡為51歲,最年輕為25歲,平均年齡39.7±±6.8。CIN Ⅰ患者最大年齡為63歲,最年輕為24歲,平均年齡40.1±±9.2。良性病歷組最大年齡為56歲,最年輕為41歲,平均年齡47.2±±3.443。使用SPSS19.0統(tǒng)計數(shù)據(jù),所有數(shù)據(jù)統(tǒng)計均采用95%置信區(qū)間,5%的顯著性水平。如P值0.05則考慮為有統(tǒng)計學(xué)差異。免疫染色為半定量法。使用Pearson檢驗(yàn)方法評價P16, P53,IMP3在各研究組中的表達(dá)。使用相關(guān)系數(shù)來了解P16,P53和IMP3的超表達(dá)與多種臨床參數(shù)的關(guān)系及各標(biāo)記之間的關(guān)系。基于各標(biāo)記物的共表達(dá),計算其敏感性和特異性并繪制P16和IMP3共表達(dá)的ROC曲線。 結(jié)果： 1.在各研究組觀察出P16,P53和IMP3的超表達(dá)不同,并具有統(tǒng)計學(xué)差異(P=0.003)。 2.檢測P16存在于細(xì)胞漿和細(xì)胞核內(nèi),對照組未顯示P16的超表達(dá)。研究組P16的表達(dá)具有差異性(P=0.024)。在不同F(xiàn)IGO分期患者中P16表達(dá)具有差異性(P=0.001)。P16的超表達(dá)與研究組密切相關(guān)。 3.除細(xì)胞核內(nèi)均發(fā)現(xiàn)P53染色,對照組未顯示P53的超表達(dá)。在研究組P53的表達(dá)具有差異性(P=0.007)。在SCC患者中,不同F(xiàn)IGO分期患者P53表達(dá)具有差異性。P53的超表達(dá)與研究組及FIG0分期密切相關(guān)(分別為ρ=0.275,P=0.002and p=0.358,P=0.008). 4.IMP3普遍存在于細(xì)胞漿中,在所有SCC患者中表現(xiàn)為高密度,而在CIN患者中為輕中密度。對照組未顯示IMP3的表達(dá)。IMP3的超表達(dá)與宮頸病變的程度有關(guān)并具有統(tǒng)計學(xué)差異(P=0.000)。在SCC患者中,不同F(xiàn)IGO分期患者IMP3表達(dá)具有差異性(P=0.030)。IMP3的超表達(dá)與FIGO分期(ρ=0.292,P=0.036)、血管浸潤(ρ=0.328,P=0.017)、陽性淋巴結(jié)(p=0.280,P=0.042)和HR-HPV感染(ρ=0.175,P=0.219)有關(guān)。 5.P16和IMP3在研究組中的表達(dá)呈正相關(guān)性,其相關(guān)性具有統(tǒng)計學(xué)差異(ρ=0.339,P=0.000)。 6.P16作為宮頸病變的獨(dú)立檢測因子其靈敏度和特異性分別為90%和50%。相似的PPV為75.2%,NPV為74.3%,陽性似然比為1.8,陰性似然比為0.2。 7.IMP3作為宮頸病變的獨(dú)立檢測因子其靈敏度和特異性分別為68.2%和92.3%。相似的PPV為93.7%,NPV為63.1%,陽性似然比為8.5,陰性似然比為0.35。 8.P16和IMP3的共表達(dá)在檢測宮頸癌前病變和宮頸癌中,敏感性為87%,特異性為87.5%。相似地PPV為93.7%,NPV為75.7%,陽性似然比為6.69和陰性似然比為0.15.ROC曲線下面積為0.969。 結(jié)論： 1.P16表達(dá)與宮頸癌具有強(qiáng)相關(guān)性。在CIN患者中P16的表達(dá)未顯示明顯相關(guān)性。 2.P53表達(dá)與宮頸病變嚴(yán)重性呈正相關(guān)。大部分病歷支持宮頸癌患者P53的免疫活性僅表現(xiàn)在少數(shù)細(xì)胞中,大部分野生型P53半衰期很短,因此很難檢測其免疫組織化學(xué)性狀。P53免疫活性可用來協(xié)助診斷腫瘤形成,但P53缺失并不能排除腫瘤的生成。 3.IMP3主要是在SCC患者中表達(dá),與能預(yù)測腫瘤侵襲性的FIGO分期、淋巴結(jié)轉(zhuǎn)移、血管浸潤密切相關(guān)。因此IMP3被認(rèn)為與腫瘤侵襲性相關(guān)。 4.IMP3表達(dá)與HR-HPV感染呈正相關(guān)。P16作為宮頸病變獨(dú)立的檢測因子具有較高的靈敏度但特異性較低,相反,IMP3具有較高的特異性,但靈敏度較低。而IMP3和P16共表達(dá)其靈敏度和特異性均明顯提高,同時,其PPV和NPV較之其獨(dú)立表達(dá)均明顯提高。通過繪制并計算P16和IMP3的共表達(dá)ROC曲線下面積為0.969,可知對宮頸癌前病變及宮頸癌的評價效果與P16和IMP3的共表達(dá)的效果相當(dāng)。
[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.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.33
本文編號：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.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R737.33
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
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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