發(fā)布時間：2018-09-09 08:35

【摘要】：研究背景及目的乳腺癌(Breast cancer)是世界上最常見的惡性腫瘤之一。目前我國雖然是乳腺癌發(fā)病率較低的國家,但隨著我國不斷發(fā)展的經(jīng)濟水平以及人們生活方式的改變、環(huán)境的變化等,乳腺癌發(fā)病歷程迅速增長。且我國人口基數(shù)比較大,發(fā)病高峰年齡較歐美國家偏低。這些因素促使我國乳腺癌發(fā)病人數(shù)迅猛增加,嚴重威脅著婦女的健康和生命。經(jīng)過多年的研究,人們發(fā)現(xiàn),雌激素受體(ER)在乳腺癌中的表達與乳腺癌發(fā)生、預(yù)后有一定的相關(guān)性。孕激素受體(PR)是雌激素與雄激素(AR)受體結(jié)合誘導(dǎo)的產(chǎn)物。PR可抑制乳腺癌細胞株的生長,亦可抑制腫瘤細胞的生長、轉(zhuǎn)移。乳腺癌患者中若PR陽性,則此患者內(nèi)分泌治療效果比較好,預(yù)后也相較好。C-erbB-2是目前人們研究的一個熱點,隨著分子生物學(xué)研究的深入,人們也不斷探索C-erbB-2在乳腺癌發(fā)生過程中所起到的作用,從而不斷完善其對相關(guān)臨床檢查和治療方法,明確C-erbB-2基因的狀況對評估乳腺癌患者預(yù)后十分重要,并有利于指導(dǎo)患者對C-erbB-2檢測陽性的病人進行Herceptin(赫賽汀)治療。Ki-67陽性指數(shù)是評估腫瘤細胞增值活性的重要指標。近年來,乳腺癌中Ki-67陽性指數(shù)的許多潛在臨床價值逐漸被認識,在乳腺癌治療方案選擇和預(yù)后評估中起著越來越重要的作用。乳腺癌轉(zhuǎn)移的主要方式是腋窩淋巴結(jié)轉(zhuǎn)移,也是影響乳腺癌預(yù)后的最主要因素。P16基因(MTS1/Ink4a)作為一種多腫瘤抑制基因,當(dāng)P16發(fā)生缺失、突變、表達異常時,就會引起P16蛋白合成障礙,從而引起細胞增值失控,導(dǎo)致腫瘤的發(fā)生。綜上所述,ER、PR、C-erbB-2、Ki-67、P16在乳腺癌組織中單個的過度表達均與乳腺癌的預(yù)后有關(guān),但單一檢測上述指標有一定的局限性,因此,本實驗檢測乳腺癌蠟塊中ER、PR、C-erbB-2、Ki-67、P16的表達水平,綜合ER、PR、C-erbB-2等的表達情況來分析P16與乳腺癌的組織學(xué)分級、病理類型,腋窩淋巴結(jié)的轉(zhuǎn)移是否有一定的相關(guān)性。主要探討P16與乳腺癌的關(guān)系及意義。材料與方法:收集乳腺癌患者切除的組織做成的蠟塊作為實驗研究的對象,患者術(shù)前均未接受放療、化療的治療。用免疫組織化學(xué)染色的方法來檢測40例乳腺癌組織蠟塊中的ER、PR、C-erbB-2、Ki-67、P16的表達水平。結(jié)果:1):P16陽性表達隨組織學(xué)分級升高而逐漸降低;P16陰性表達隨組織學(xué)分級升高而逐漸升高。2):P16導(dǎo)管原位癌中表達強度比其他組織學(xué)類型表達要強。3):P16與C-erbB-2之間呈負向關(guān)系4):P16與Ki-67之間無相關(guān)性,P16在三陰乳腺癌與非三陰乳腺癌中的表達無區(qū)別意義5):腋窩淋巴結(jié)轉(zhuǎn)移組P16陽性表達率低于無腋窩淋巴結(jié)轉(zhuǎn)移組結(jié)論:P16與乳腺癌的組織學(xué)分級有關(guān),與C-erbB-2之間呈負向關(guān)系,還和淋巴結(jié)轉(zhuǎn)移有一定的關(guān)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.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.9

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