P16、OLFM4在宫颈上皮内瘤变中的表达及其诊断意义
发布时间：2018-08-03 21:38
【摘要】：在世界上,宫颈癌被认为是女性恶性肿瘤中最常见的疾病之一,仅次于乳腺癌,但宫颈癌是唯一能够早期预防和早期诊断的恶性肿瘤。宫颈上皮内瘤变(Cervical Intraepithelial Neoplasia,CIN)是宫颈癌前病变的主要疾病状态,对宫颈癌的发生具有重要的推动作用。为了降低宫颈癌的发生率和死亡率,改善预后,如果临床医生能够针对癌前状态及时给予干扰及阻断,将病灶完全清除,对宫颈癌的防治有重要意义。因此,在宫颈病变的筛查中,生物标志物作为一种特异性物质已经逐渐地被应用,这会对宫颈癌的预防和治疗会起到重要的作用。P16INK4A基因是一种抑癌基因,即人类周期素依赖性激酶(cyclin dependent kinase,CDK)4抑制因子(p16)基因,它所表达蛋白的是一种抑癌蛋白,即P16蛋白。在宫颈病变中,P16INK4A的表达随着宫颈病变程度的增加而升高。人类嗅素蛋白4(olfactomedin4,OLFM4)是一种新的抗凋亡蛋白,可促进肿瘤细胞的生长,同时能准确地反映宫颈上皮细胞的增殖和分化情况,能够很好地区分正常宫颈组织与宫颈上皮内瘤变(CIN),如果将这两种生物标志物联合检测能更好地辅助宫颈病变的诊断,预测宫颈病变级别及进展,从而降低患者的经济支出,进而也减轻患者的精神负担。研究对象是2015至2016年曾因宫颈病变就诊于河北北方学院附属第一医院妇科门诊,并于妇科门诊手术室行阴道镜下宫颈活检术的病理标本,年龄范围为21-68岁。实验组是阴道镜下宫颈活检病理诊断结果为宫颈上皮内瘤变(CIN)的病理标本,并依据组织学诊断结果将其分为三个亚组,其中宫颈上皮内瘤变I级(cervical intraepithelial neoplasia grade 1,CINI)50例,宫颈上皮内瘤变II级(cervical intraepithelial neoplasia grade 2,CINII)50例,宫颈上皮内瘤变III级(cervical intraepithelial neoplasia grade3,CINIII)50例。阴道镜宫颈活检术均由专科医生操作,正常对照组30例是因子宫良性病变切除子宫的病理标本。采用免疫组织化学法(immunohistochemistry,IHC)对其病理标本进行检测。实验组中P16和OLFM4的阳性表达率分别为88.67%、87.33%,而对照组中P16和OLFM4的阳性表达率分别为26.67%、20.00%。实验组均高于对照组,所以,P16的阳性表达率具有显著的统计学差异(χ2=58.463,P0.05),OLFM4的阳性表达率具有显著的统计学差异(χ2=63.459,P0.05)。P16在实验组(CINI、CINII、CINIII)中阳性表达率分别为76.00%、90.00%和100.00%,有显著性差异(χ2=112.582,P0.05),每两组间比较P16的表达均有统计学差异(P0.05)。OLFM4在实验组(CINI、CINII、CINIII)中阳性表达率分别为76.00%、86.00%和100.00%,有统计学差异(χ2=124.866,P0.05),且每两组间比较OLFM4的表达均有统计学意义(P0.05)。总之,CINIII组阳性表达率最高、其次是CINII组阳性表达率、CINI组阳性表达率最低。从以上数据分析,P16的表达阳性率与宫颈上皮内瘤变(CIN)病变程度有显著的相关性(r=0.613,P0.05),OLFM4的表达阳性率与宫颈上皮内瘤变(CIN)病变程度也有显著的相关性(r=0.380,P0.05),可知,宫颈上皮内瘤变(CIN)病变程度越严重,P16和OLFM4阳性表达率越高。从实验组P16和OLFM4表达情况相关性分析可知,P16和OLFM4的表达也存在相关性,P16的阳性表达率越高,则OLFM4的阳性表达率也随之增高。根据spearman相关分析,P16和OLFM4的联合表达情况与宫颈病变程度有显著性的相关(r=0.862,P0.05)。P16和OLFM4联合表达率在CINI、CINII、CINIII各组中为0、70.00%、100%,P16和OLFM4联合表达率越高,宫颈病变程度越高。综上所述,P16、OLFM4的表达与宫颈上皮内瘤变(CIN)的严重程度呈正向关系。并且,P16、OLFM4的高表达与宫颈上皮内瘤变(CIN)临床分级呈正向相关关系,将有助于提高对宫颈上皮内瘤变(CIN)诊断的一致性,从而更好地诊断和预防宫颈上皮内瘤变(CIN)。同时,P16、OLFM4联合表达率随宫颈病变程度的加重而升高,其联合检测为宫颈癌的筛查的分流管理,疾病的早期诊断及治疗,尤其是可以更好地分流CINII,从而提供个体化诊疗方案非常重要。
[Abstract]:In the world, cervical cancer is considered to be one of the most common diseases in female malignant tumors, second only to breast cancer, but cervical cancer is the only malignant tumor that can be prevented early and early diagnosis. Cervical intraepithelial neoplasia (Cervical Intraepithelial Neoplasia, CIN) is the main disease state of precancerous lesions of the cervix and the occurrence of cervical cancer. In order to reduce the incidence and mortality of cervical cancer and improve the prognosis, it is of great significance for the prevention and control of cervical cancer if the clinician can give timely interference and interruption to the precancerous condition, and it is of great significance for the prevention and treatment of cervical cancer. Gradually applied, this will play an important role in the prevention and treatment of cervical cancer. The.P16INK4A gene is a tumor suppressor gene, the cyclin dependent kinase (CDK) 4 inhibitory factor (p16) gene, which expresses a tumor suppressor white egg white, that is, the P16 protein. In cervical lesions, P16INK4A expression along with the expression of P16INK4A Human olfactory protein 4 (olfactomedin4, OLFM4) is a new anti apoptotic protein, which can promote the growth of tumor cells, and can accurately reflect the proliferation and differentiation of cervical epithelial cells. It can be well divided into normal cervical and cervical intraepithelial neoplasia (CIN), if these two species are to be used. Combined detection of markers can better assist the diagnosis of cervical lesions, predict the level and progress of cervical lesions, thus reduce the economic expenditure of the patients, and then reduce the mental burden of the patients. The study was from 2015 to 2016 in the gynecologic outpatient of First Affiliated Hospital of Hebei North University because of cervical lesions, and in the operation room of gynecologic outpatient department. The pathological specimen of cervical biopsy under colposcopy was 21-68 years old. The experimental group was a pathological specimen of cervical intraepithelial neoplasia (CIN) of cervical biopsy under colposcopy, and was divided into three subgroups according to the histological diagnosis, of which the cervical intraepithelial neoplasia was I (cervical intraepithelial neoplasia grade 1,) CINI) 50 cases, cervical intraepithelial neoplasia (cervical intraepithelial neoplasia grade 2, CINII) in 50 cases, cervical intraepithelial neoplasia III grade (cervical intraepithelial neoplasia Grade3,) 50 cases. Colposcopy cervical biopsy was operated by a specialist, and 30 cases of the normal group were pathological specimens of the uterus due to benign uterine lesions. The positive expression rate of P16 and OLFM4 in the experimental group was 88.67%, 87.33%, respectively, and the positive expression rate of P16 and OLFM4 in the control group was 26.67%, respectively, and the 20.00%. experimental group was higher than the control group. Therefore, the positive expression rate of P16 was statistically significant difference. The positive expression rate of OLFM4 was significantly different (x 2=63.459, P0.05).P16 in the experimental group (CINI, CINII, CINIII) in the experimental group (CINI, CINII, CINIII) was 76%, 90% and 100%, respectively (chi, 2=112.582, P0.05), and there were significant differences in the expression of P16 in the two groups. The positive expression rate in CINII, CINIII) was 76%, 86% and 100% respectively (x 2=124.866, P0.05), and the expression of OLFM4 in each two groups was statistically significant (P0.05). In a word, the positive rate of CINIII group was the highest, followed by the positive rate of CINII group, and the lowest positive rate in the CINI group. From the above data analysis, the P16 table There was a significant correlation between the positive rate and the degree of cervical intraepithelial neoplasia (CIN) (r=0.613, P0.05). The positive rate of OLFM4 expression was also significantly correlated with the degree of cervical intraepithelial neoplasia (CIN) (r=0.380, P0.05). It is known that the more serious the cervical intraepithelial neoplasia (CIN), the higher the positive expression rate of P16 and OLFM4. From experimental group P16. The correlation analysis of the expression of OLFM4 showed that the expression of P16 and OLFM4 also existed, the higher the positive expression rate of P16, the positive expression rate of OLFM4 increased. According to the Spearman correlation analysis, the joint expression of P16 and OLFM4 had a significant correlation with the degree of cervical lesions (r=0.862, P0.05).P16 and OLFM4 joint expression rate The higher the combined expression rate of 0,70.00%, 100%, P16 and OLFM4 in NI, CINII, and CINIII, the higher the degree of cervical lesions. To sum up, the expression of P16, OLFM4 has a positive relationship with the severity of cervical intraepithelial neoplasia (CIN). Moreover, the high expression of P16, OLFM4 is positively related to the clinical classification of cervical intraepithelial neoplasia (CIN), and will help to improve The diagnosis and prevention of cervical intraepithelial neoplasia (CIN) is consistent to better diagnose and prevent cervical intraepithelial neoplasia (CIN). At the same time, the combined expression rate of P16 and OLFM4 increases with the aggravation of the degree of cervical lesions, which is combined to detect the shunt management of cervical cancer screening, early diagnosis and treatment of the disease, especially to divert CINII better. It is very important to provide an individualized diagnosis and treatment scheme.
【学位授予单位】：河北北方学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33
本文编号：2163068
[Abstract]:In the world, cervical cancer is considered to be one of the most common diseases in female malignant tumors, second only to breast cancer, but cervical cancer is the only malignant tumor that can be prevented early and early diagnosis. Cervical intraepithelial neoplasia (Cervical Intraepithelial Neoplasia, CIN) is the main disease state of precancerous lesions of the cervix and the occurrence of cervical cancer. In order to reduce the incidence and mortality of cervical cancer and improve the prognosis, it is of great significance for the prevention and control of cervical cancer if the clinician can give timely interference and interruption to the precancerous condition, and it is of great significance for the prevention and treatment of cervical cancer. Gradually applied, this will play an important role in the prevention and treatment of cervical cancer. The.P16INK4A gene is a tumor suppressor gene, the cyclin dependent kinase (CDK) 4 inhibitory factor (p16) gene, which expresses a tumor suppressor white egg white, that is, the P16 protein. In cervical lesions, P16INK4A expression along with the expression of P16INK4A Human olfactory protein 4 (olfactomedin4, OLFM4) is a new anti apoptotic protein, which can promote the growth of tumor cells, and can accurately reflect the proliferation and differentiation of cervical epithelial cells. It can be well divided into normal cervical and cervical intraepithelial neoplasia (CIN), if these two species are to be used. Combined detection of markers can better assist the diagnosis of cervical lesions, predict the level and progress of cervical lesions, thus reduce the economic expenditure of the patients, and then reduce the mental burden of the patients. The study was from 2015 to 2016 in the gynecologic outpatient of First Affiliated Hospital of Hebei North University because of cervical lesions, and in the operation room of gynecologic outpatient department. The pathological specimen of cervical biopsy under colposcopy was 21-68 years old. The experimental group was a pathological specimen of cervical intraepithelial neoplasia (CIN) of cervical biopsy under colposcopy, and was divided into three subgroups according to the histological diagnosis, of which the cervical intraepithelial neoplasia was I (cervical intraepithelial neoplasia grade 1,) CINI) 50 cases, cervical intraepithelial neoplasia (cervical intraepithelial neoplasia grade 2, CINII) in 50 cases, cervical intraepithelial neoplasia III grade (cervical intraepithelial neoplasia Grade3,) 50 cases. Colposcopy cervical biopsy was operated by a specialist, and 30 cases of the normal group were pathological specimens of the uterus due to benign uterine lesions. The positive expression rate of P16 and OLFM4 in the experimental group was 88.67%, 87.33%, respectively, and the positive expression rate of P16 and OLFM4 in the control group was 26.67%, respectively, and the 20.00%. experimental group was higher than the control group. Therefore, the positive expression rate of P16 was statistically significant difference. The positive expression rate of OLFM4 was significantly different (x 2=63.459, P0.05).P16 in the experimental group (CINI, CINII, CINIII) in the experimental group (CINI, CINII, CINIII) was 76%, 90% and 100%, respectively (chi, 2=112.582, P0.05), and there were significant differences in the expression of P16 in the two groups. The positive expression rate in CINII, CINIII) was 76%, 86% and 100% respectively (x 2=124.866, P0.05), and the expression of OLFM4 in each two groups was statistically significant (P0.05). In a word, the positive rate of CINIII group was the highest, followed by the positive rate of CINII group, and the lowest positive rate in the CINI group. From the above data analysis, the P16 table There was a significant correlation between the positive rate and the degree of cervical intraepithelial neoplasia (CIN) (r=0.613, P0.05). The positive rate of OLFM4 expression was also significantly correlated with the degree of cervical intraepithelial neoplasia (CIN) (r=0.380, P0.05). It is known that the more serious the cervical intraepithelial neoplasia (CIN), the higher the positive expression rate of P16 and OLFM4. From experimental group P16. The correlation analysis of the expression of OLFM4 showed that the expression of P16 and OLFM4 also existed, the higher the positive expression rate of P16, the positive expression rate of OLFM4 increased. According to the Spearman correlation analysis, the joint expression of P16 and OLFM4 had a significant correlation with the degree of cervical lesions (r=0.862, P0.05).P16 and OLFM4 joint expression rate The higher the combined expression rate of 0,70.00%, 100%, P16 and OLFM4 in NI, CINII, and CINIII, the higher the degree of cervical lesions. To sum up, the expression of P16, OLFM4 has a positive relationship with the severity of cervical intraepithelial neoplasia (CIN). Moreover, the high expression of P16, OLFM4 is positively related to the clinical classification of cervical intraepithelial neoplasia (CIN), and will help to improve The diagnosis and prevention of cervical intraepithelial neoplasia (CIN) is consistent to better diagnose and prevent cervical intraepithelial neoplasia (CIN). At the same time, the combined expression rate of P16 and OLFM4 increases with the aggravation of the degree of cervical lesions, which is combined to detect the shunt management of cervical cancer screening, early diagnosis and treatment of the disease, especially to divert CINII better. It is very important to provide an individualized diagnosis and treatment scheme.
【学位授予单位】：河北北方学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.33
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