乳腺癌患者癌组织及咽部HPV感染的临床研究

发布时间：2018-01-27 09:18

本文关键词： 乳腺癌人乳头瘤病毒二代杂交捕获技术 P16　出处：《山东大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的：进一步探究乳腺恶性肿瘤与人乳头瘤病毒(human papillomavirus, HPV)之间的关系,探索咽部来源的HPV是否为乳腺癌中HPV可能的感染途径之一以及寻找乳腺组织中理想的HPV监测标志物,从而为乳腺癌的一级预防、早期诊断和治疗新思路提供相应的循证医学证据。方法：本研究纳入了2015年1月25日至2015年12月27日时间段内就诊于山东大学齐鲁医院乳腺外科住院接受手术治疗的94名患者的乳腺癌组织、良性乳腺肿瘤组织或乳头溢液样本,其中67名患者同时收集了咽部脱落细胞,利用二代杂交捕获技术(hybrid capture 2, HC2)进行组织样本的13种高危型HPV(high-risk HPV, HR-HPV)检测,对HC2检测阳性的样本进行乳腺病变组织P16和Ki-67免疫组化检测。利用SPSS 19.0软件对上述资料进行统计学分析。结果：1.乳腺癌组织样本73例,所有样本HC2检测均未查见HR-HPV感染。2.乳腺良性肿瘤组织病变样本12例,检出HR-HPV阳性1例,为乳腺导管扩张症,阳性率8.3%。3.本组病例中有67例患者同时检测咽部HPV感染,咽部HR-HPV感染7例(10.4%),且不与乳腺组织同时感染。运用四格表Fisher确切概率法对乳腺和咽部HR-HPV感染情况分析发现无显著性统计学差异(P0.05)。并对其中59例乳腺癌患者进行临床特点及组织病理学特性分析,发现咽部HR-HPV感染在不同年龄组患者中存在显著统计学差异(P0.05),年龄小于等于40岁年龄组患者咽部感染HR-HPV的比率(37.5%)高于大于40岁年龄组患者(7.8%)。4.9例乳头溢液样本,均未查见HR-HPV感染。5.HC2检测中发现阳性(乳房肿块或咽部)的病例共8例,进行乳腺病变组织P16和Ki-67免疫组化检验,发现7例咽部HC2阳性的病例中乳腺癌组织有6例P16细胞核呈现不同水平的阳性表达,2例P16呈现细胞浆阳性(1例为强阳性)。1例HPV阳性的乳腺导管扩张症病例中P16在细胞核与细胞浆中均表达强阳性。Ki-67在上述8例出现了不同程度的表达。结论：1.HC2技术是检测HPV的较好方法,但目前应用于乳腺组织中灵敏度有待提高。2.乳头溢液中未检测到HPV感染,通过乳头溢液检测乳腺HPV感染的临床应用价值需进一步大样本研究。3.乳腺导管扩张症中存在HPV感染,提示HPV可能通过乳孔、乳管进入乳腺组织中直接感染。4.咽部与乳腺组织不同时存在HPV感染,研究支持乳腺组织与人体其他部位不同时感染HPV的假说,5.P16在HPV阳性的乳腺组织中表达较高,有望成为乳腺组织中较敏感的HPV间接检测指标。
[Abstract]:Objective: to investigate the relationship between breast malignant tumors and human papillomavirus (HPVs). To explore whether pharyngeal HPV is one of the possible routes of HPV infection in breast cancer and to find out the ideal marker of HPV monitoring in breast tissue so as to provide primary prevention for breast cancer. New ideas for early diagnosis and treatment provide appropriate evidence-based medical evidence. Methods:. This study included the breast cancer tissues of 94 patients admitted to the Department of Breast surgery, Qilu Hospital, Shandong University during the period from January 25th 2015 to December 27th 2015. Samples of benign breast tumor tissues or nipple discharge were collected from 67 patients with exfoliated pharynx cells and hybrid capture 2 was used to capture the cells. HC2) was used to detect 13 high risk HPV(high-risk HPVs (HR-HPVs) in tissue samples. HC2 positive samples were detected by P16 and Ki-67 immunohistochemistry. The above data were statistically analyzed by SPSS 19.0 software. Results:. 1. Tissue samples of 73 cases of breast cancer. HR-HPV infection was not detected by HC2 in all samples. 12 cases of benign breast neoplasms were detected and 1 case was positive for HR-HPV, which was mammary ductal dilatation. In this group, 67 cases were detected for pharyngeal HPV infection and 7 cases for pharyngeal HR-HPV infection (10.4%). The results showed that there was no significant difference in HR-HPV infection between breast and pharynx (P0.05) by using the exact probability method of four-cell table Fisher to analyze the infection of breast and pharynx. The clinical and histopathological characteristics of 59 cases of breast cancer were analyzed. It was found that there was significant difference in pharyngeal HR-HPV infection among patients of different age groups (P0.05). The rate of pharyngeal infection with HR-HPV in the age group less than 40 years old (37.5%) was higher than that in the older group (7.8%). 4.9 cases of nipple discharge were detected. There were 8 cases with positive HR-HPV infection (breast mass or pharynx). P16 and Ki-67 were detected by immunohistochemistry. In 7 cases of pharyngeal HC2 positive, there were 6 cases of P16 cell nuclear positive expression in breast cancer tissue. 2 cases of P16 showed cytoplasmic positive and 1 case was strongly positive. The positive expression of P16 in the nuclei and cytoplasm of 1 cases of breast ductal dilatation with HPV positive was strong. Ki-67 was expressed in 8 cases mentioned above. Conclusion:. 1.HC2 technique is a good method to detect HPV. However, the sensitivity in breast tissue needs to be improved. 2. No HPV infection was detected in nipple discharge. The clinical value of detecting breast HPV infection by nipple discharge needs further large sample study .3. there is HPV infection in mammary ductal dilatation, suggesting that HPV may pass through mammary foramen. HPV infection does not exist in the pharynx and mammary tissue at the same time. The study supports the hypothesis that the breast tissue is not infected with HPV at the same time as the other parts of the human body. 5. The expression of P16 is higher in breast tissues with HPV positive, which is expected to be a sensitive index for indirect detection of HPV in breast tissues.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R737.9

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