P16在乳腺癌中的表达

发布时间：2018-09-09 08:35

【摘要】：研究背景及目的乳腺癌(Breast cancer)是世界上最常见的恶性肿瘤之一。目前我国虽然是乳腺癌发病率较低的国家,但随着我国不断发展的经济水平以及人们生活方式的改变、环境的变化等,乳腺癌发病历程迅速增长。且我国人口基数比较大,发病高峰年龄较欧美国家偏低。这些因素促使我国乳腺癌发病人数迅猛增加,严重威胁着妇女的健康和生命。经过多年的研究,人们发现,雌激素受体(ER)在乳腺癌中的表达与乳腺癌发生、预后有一定的相关性。孕激素受体(PR)是雌激素与雄激素(AR)受体结合诱导的产物。PR可抑制乳腺癌细胞株的生长,亦可抑制肿瘤细胞的生长、转移。乳腺癌患者中若PR阳性,则此患者内分泌治疗效果比较好,预后也相较好。C-erbB-2是目前人们研究的一个热点,随着分子生物学研究的深入,人们也不断探索C-erbB-2在乳腺癌发生过程中所起到的作用,从而不断完善其对相关临床检查和治疗方法,明确C-erbB-2基因的状况对评估乳腺癌患者预后十分重要,并有利于指导患者对C-erbB-2检测阳性的病人进行Herceptin(赫赛汀)治疗。Ki-67阳性指数是评估肿瘤细胞增值活性的重要指标。近年来,乳腺癌中Ki-67阳性指数的许多潜在临床价值逐渐被认识,在乳腺癌治疗方案选择和预后评估中起着越来越重要的作用。乳腺癌转移的主要方式是腋窝淋巴结转移,也是影响乳腺癌预后的最主要因素。P16基因(MTS1/Ink4a)作为一种多肿瘤抑制基因,当P16发生缺失、突变、表达异常时,就会引起P16蛋白合成障碍,从而引起细胞增值失控,导致肿瘤的发生。综上所述,ER、PR、C-erbB-2、Ki-67、P16在乳腺癌组织中单个的过度表达均与乳腺癌的预后有关,但单一检测上述指标有一定的局限性,因此,本实验检测乳腺癌蜡块中ER、PR、C-erbB-2、Ki-67、P16的表达水平,综合ER、PR、C-erbB-2等的表达情况来分析P16与乳腺癌的组织学分级、病理类型,腋窝淋巴结的转移是否有一定的相关性。主要探讨P16与乳腺癌的关系及意义。材料与方法:收集乳腺癌患者切除的组织做成的蜡块作为实验研究的对象,患者术前均未接受放疗、化疗的治疗。用免疫组织化学染色的方法来检测40例乳腺癌组织蜡块中的ER、PR、C-erbB-2、Ki-67、P16的表达水平。结果:1):P16阳性表达随组织学分级升高而逐渐降低;P16阴性表达随组织学分级升高而逐渐升高。2):P16导管原位癌中表达强度比其他组织学类型表达要强。3):P16与C-erbB-2之间呈负向关系4):P16与Ki-67之间无相关性,P16在三阴乳腺癌与非三阴乳腺癌中的表达无区别意义5):腋窝淋巴结转移组P16阳性表达率低于无腋窝淋巴结转移组结论:P16与乳腺癌的组织学分级有关,与C-erbB-2之间呈负向关系,还和淋巴结转移有一定的关系。
[Abstract]:Background and objective (Breast cancer) is one of the most common malignant tumors in the world. Although the incidence of breast cancer in China is relatively low, the incidence of breast cancer has increased rapidly with the development of economic level, the change of people's lifestyle and the change of environment. And the population base of our country is relatively large, the peak age of incidence is lower than that of European and American countries. These factors have led to a rapid increase in breast cancer incidence in China, which is a serious threat to women's health and life. After years of research, it has been found that the expression of estrogen receptor (ER) in breast cancer is related to the occurrence and prognosis of breast cancer. Progesterone receptor (PR) is the product of estrogen binding with androgen (AR) receptor. PR can inhibit the growth of breast cancer cell line, but also inhibit the growth and metastasis of tumor cells. If PR is positive in breast cancer patients, the endocrine therapy effect is better and the prognosis is relatively good. C-erbB-2 is a hot research topic. With the development of molecular biology, People have also been exploring the role of C-erbB-2 in the process of breast cancer, so as to improve its clinical examination and treatment methods, and clarify the status of C-erbB-2 gene in the evaluation of breast cancer patients prognosis is very important. It is helpful to instruct patients to carry out Herceptin (Herceptin) therapy. Ki-67 positive index is an important index to evaluate the proliferative activity of tumor cells. In recent years, many potential clinical values of Ki-67 positive index in breast cancer have been gradually recognized, which plays an increasingly important role in breast cancer treatment options and prognosis evaluation. The main way of metastasis of breast cancer is axillary lymph node metastasis. P16 gene (MTS1/Ink4a) is the most important factor that affects the prognosis of breast cancer. This will cause P16 protein synthesis obstacles, thus causing cell proliferation out of control, leading to tumorigenesis. To sum up, the single overexpression of C-erbB-2 and Ki-67-P16 in breast cancer tissues is related to the prognosis of breast cancer, but there are some limitations in the single detection of the above indexes. Therefore, the expression level of ER,PR,C-erbB-2,Ki-67,P16 in breast cancer wax mass was detected in this experiment. To analyze the correlation between P16 and histological grade, pathological type, axillary lymph node metastasis or not. The relationship between P16 and breast cancer and its significance were discussed. Materials and methods: paraffin lumps made from resected tissues of breast cancer patients were collected as experimental subjects. The patients were not treated with radiotherapy and chemotherapy before operation. Immunohistochemical staining was used to detect the expression of ER,PR,C-erbB-2,Ki-67,P16 in paraffin masses of 40 cases of breast cancer. Results the positive expression of P16 decreased gradually with the increase of histological grade, and the negative expression of P16 increased gradually with the increase of histological grade. 2) the positive expression of P16 was stronger than that of other histological types in carcinoma in situ. 3) the negative correlation between P16 and C-erbB-2 was negative. Line 4) there was no correlation between P16 and Ki-67. 5): the positive expression rate of P16 in axillary lymph node metastasis group was lower than that in non-axillary lymph node metastasis group. There is a negative relationship between C-erbB-2 and lymph node metastasis.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9

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