【作者】 张莉；

【导师】 马榕；

【作者基本信息】 山东大学 ， 外科学·普通外科（专业学位）， 2020， 硕士

【摘要】 目的通过对乳头溢液、初乳、血清中PRL水平的检测分析,初步研究良恶性乳头溢液、初乳中PRL的水平及乳头溢液患者血清和乳头溢液中PRL水平的关系,从而为伴随乳头溢液的乳腺疾病的发生发展提供新的研究思路,这将在该部分患者的一级预防、早期诊断和治疗等方面具有重要意义。材料与方法乳头溢液标本及对应的血清标本取自2018年1月至2019年6月于山东大学齐鲁医院乳腺外科就诊并行手术治疗的患者。经过筛选符合入组条件的66例乳头溢液患者的乳头溢液及血清标本,包括52例良性乳腺疾病和14例乳腺癌;收集2018年5月至2018年12月于山东大学齐鲁医院产科分娩的50例产妇的双侧乳房初乳标本为健康对照;用来分析不伴乳头溢液乳腺疾病患者血清PRL水平的血清标本取自2019年1月至2019年12月于山东大学齐鲁医院乳腺外科就诊并行手术治疗的277例不伴乳头溢液的乳腺疾病患者,包括133例良性乳腺疾病和144例乳腺癌。所有标本均采用三明治式电化学免疫发光分析法(ECLIA)对PRL的浓度进行检测,运用统计学方法分析数据。本研究中的P值均为双向,且P值小于0.05被认为是具有统计学意义。结果第一部分乳头溢液患者血清、乳头溢液及初乳中PRL检测水平分析1.乳头溢液患者血清中PRL检测水平分析:(1)66例乳头溢液患者血清标本中PRL检测水平中位数为21.81ng/ml,四分位数分别为11.93,21.81,32.42ng/ml。52例良性乳头溢液患者血清标本中PRL检测水平中位数为21.97ng/ml,四分位数分别为13.84、21.97、33.26ng/ml。14例恶性乳头溢液患者血清标本中PRL检测水平中位数为13.28ng/ml,四分位数分别为 7.95、13.28、28.2ng/ml。(2)采用两独立样本Mann-Whitney U检验比较良恶性乳头溢液患者血清中PRL检测水平无显著统计学差异,P>0.05。(3)66例乳头溢液患者中有43.94%(29/66)为高PRL血症(PRL>23.30ng/ml),良性乳头溢液患者中有44.23%(23/52)为高PRL血症,恶性乳头溢液患者中有42.86%(6/14)为高PRL血症。(4)采用卡方检验比较良恶性乳头溢液患者高PRL血症的发生率无显著统计学差异,P>0.052.乳头溢液中PRL检测水平分析:(1)66例乳头溢液标本中PRL水平的中位数为26.20ng/ml,四分位数分别为15.35、26.20、36.65ng/ml。52例良性乳头溢液标本中PRL水平中位数25.40ng/ml,四分位数分别为17.25、25.40、43.35ng/ml。14例恶性乳头溢液标本中PRL水平测量数值为正态分布资料,其均数±标准差为23.00±10.71ng/ml。(2)采用两独立样本Mann-Whitney U检验比较良恶性乳溢液中PRL检测水平无显著统计学差异,P>0.05。3.乳头溢液标本和对应血清标本中PRL检测水平的相关性及差异:(1)采用Spearman相关性分析乳头溢液及其对应血清标本PRL表达水平相关性显著,且为正相关,r=0.534,P<0.05。(2)采用配对设计的Wilcoxon符号秩和检验比较乳头溢液标本和对应血清标本中PRL检测水平有显著统计学差异,P<0.05。乳头溢液中PRL水平明显高于对应血清中PRL水平。4.初乳中PRL检测水平分析及乳头溢液和初乳中PRL检测水平差异(1)50例受试者左右两侧初乳标本PRL检测水平测定结果无显著统计学差异,双侧初乳标本PRL检测水平测量数值平均数为正态分布资料,其均数±标准差为 68.80±39.00ng/ml。(2)采用两独立样本Mann-Whitney U检验比较乳头溢液标本和初乳标本中PRL检测水平有显著统计学差异,P<0.05,乳头溢液中PRL水平低于初乳中PRL水平。第二部分不伴乳头溢液乳腺疾病患者血清中PRL检测水平分析1.133例良性患者中有26.32%(35/133)为高PRL血症,144例乳腺癌患者中 31.25%(45/144)为高 PRL 血症。2.采用卡方检验比较良恶性乳腺疾病患者高PRL血症的发生率无显著统计学差异,P>0.05。3.采用两独立样本Mann-Whitney U检验比较良恶性乳腺疾病血清标本中PRL检测水平无显著统计学差异,P>0.05。第三部分 伴乳头溢液及不伴乳头溢液乳腺疾病患者血清PRL检测水平的差异1.66例伴乳头溢液及277例不伴乳头溢液的乳腺疾病患者血清中PRL检测水平的差异性(1)采用两独立样本Mann-Whitney U检验定量比较伴乳头溢液及不伴乳头溢液的乳腺疾病患者血清中PRL检测水平的差异,两组患者血清中PRL检测水平具有明显差异,P<0.05,伴乳头溢液乳腺疾病患者血清中PRL检测水平明显高于不伴乳头溢液者。(2)采用卡方检验定性比较伴乳头溢液与不伴乳头溢液的乳腺疾病患者高PRL血症的发生率,结果显示高PRL血症在伴有乳头溢液乳腺疾病中的发生率明显高于不伴乳头溢液乳腺疾病患者,P<0.05。2.14例伴乳头溢液及144例不伴乳头溢液的乳腺癌患者血清PRL检测水平的差异(1)采用两独立样本Mann-Whitney U检验定量比较伴乳头溢液及不伴乳头溢液的乳腺癌患者血清中PRL检测水平没有明显统计学差异,P>0.05。(2)采用卡方检验定性比较伴乳头溢液及不伴乳头溢液的乳腺癌患者高PRL血症的发生率无显著统计学差异,P>0.05。3.52例伴乳头溢液及133例不伴乳头溢液的良性乳腺疾病患者血清中PRL检测水平的差异(1)采用两独立样本Mann-Whitney U检验定量比较伴乳头溢液及不伴乳头溢液的良性乳腺疾病患者血清中PRL检测水平的差异,P<0.05,两组患者血清中PRL检测水平具有明显差异,伴乳头溢液组血清中PRL检测水平明显高于不伴乳头溢液组。(2)采用卡方检验定性比较伴乳头溢液及不伴乳头溢液的良性乳腺疾病患者高PRL血症的发生率,结果显示高PRL血症在伴有乳头溢液乳腺疾病患者中的发生率明显高于不伴乳头溢液乳腺疾病患者,P<0.05。结论1.乳头溢液中PRL水平明显高于对应血清中PRL水平,提示PRL在乳管内局部有浓聚,其具体机制还有待后续的实验研究。2.乳头溢液及其对应血清标本中PRL表达水平相关性显著,且为正相关,乳头溢液中PRL可能受到血清中PRL的影响。3.伴乳头溢液的乳腺疾病患者血清中PRL检测水平明显高于不伴有乳头溢液的乳腺疾病患者,提示PRL可能与乳头溢液疾病的发生存在关系。4.良恶性乳腺疾病患者血清及乳头溢液标本PRL检测水平无显著统计学差异,检测血清及乳头溢液中PRL水平对鉴别良恶性乳腺疾病的作用还需进一步研究。5.初乳标本中含有高水平的PRL,且初乳中PRL表达水平明显高于乳头溢液,PRL在生理性和病理性乳头溢液中可能发挥不同的作用。更多还原

【Abstract】 ObjectiveThrough the detection of PRL levels in nipple discharge,colostrum and serum,we hopes to preliminarily study the relationship between benign and malignant nipple discharge,colostrum PRL level,and the relationship between serum and nipple discharge PRL levels in patients with nipple discharge,so as to provide new research ideas for the occurrence and development of breast diseases accompanied by nipple discharge,which will be of great significance to the primary prevention,early diagnosis and treatment of these patientsAll samples were detected for PRL by sandwich electrochemiluminescence assay(ECLIA).and the data were analyzed by statistical method.In this study,all P values are bi-directional,and P values less than 0.05 are considered to be statistically significant.Materials and MethodsNipple discharge and corresponding serum samples were taken from patients who were treated in the Department of Breast surgery in Qilu Hospital of Shandong University from January 2018 to June 2019.After screening,nipple discharge and serum samples were obtained from 66 patients with nipple discharge,including 52 cases of benign breast diseases and 14 cases of breast cancerThe bilateral breast colostrum samples of 50 parturients in the Department of Obstetrics,Qilu Hospital of Shandong University from May 2018 to December 2018 were collected as healthy controls.The serum PRL levels of patients with breast diseases without nipple discharge were collected from January 2019 to December 2019 in the Department of Breast surgery of Qilu Hospital of Shandong University,including 133 cases of benign breast diseases and 144 cases of breast cancer.The level of PRL in all samples was detected by sandwich electrochemiluminescence assay(ECLIA),and the data were analyzed by statistical method.In this study,all P values are bi-directional,and P values less than 0.05 are considered to be statistically significant.ResultsThe first part Analysis of PRL levels in serum,nipple discharge and colostrum in patients with nipple discharge1.Analysis of serum PRL level in patients with nipple discharge:(1)The median level of PRL in serum samples of 66 patients with nipple discharge was 22.21ng/ml,and the quartile was 21.81ng/ml and 32.42ng/ml,respectively.The median level of PRL in serum samples of 52 patients with benign nipple discharge was 21.97ng/ml,and the quartiles were 13.84ng/m,21.97ng/m and 33.26ng/ml,respectively.The median level of PRL in serum samples of 14 patients with malignant nipple discharge was 13.28ng/ml,and the quartiles were 7.95ng/ml,13.28ng/ml and 28.2ng/ml,respectively.(2)There was no significant difference in serum PRL levels between benign and malignant nipple discharge patients by Mann-Whitney U test,(P>0.05).(3)43.94%(29/66)of the patients with nipple discharge were hyperprolactinemia,44.23%(23/52)of the patients with benign nipple discharge were hyperprolactinemia,and 42.86%(6/14)of the patients with malignant nipple discharge were hyperprolactinemia.(4)There was no significant difference in the incidence of hyperprolactinemia in patients with benign and malignant nipple discharge by chi-square test,P>0.05。2.Analysis of PRL detection level in nipple discharge(1)In 66 cases of nipple discharge,the median of PRL level was 26.20ng/ml,and the quartile was 15.35ng/ml,26.20ng/ml and 36.65ng/ml.In 52 cases of benign nipple discharge,the median of PRL level was 25.40ng/ml,and the quartile was 17.25ng/ml,25.40ng/ml and 43.35ng/ml.In 14 cases of malignant nipple discharge,the measured value of PRL level was normal distribution data,and the mean±standard deviation was 23.00±10.71ng/ml(2)There was no significant difference in the level of PRL between benign and malignant nipple discharge detected by two independent samples of Mann-Whitney,P>0.05.3.Correlation and difference of PRL detection level between nipple discharge and corresponding serum:(1)Spearman correlation analysis showed that there was a significant correlation between the level of PRL in nipple discharge and its corresponding serum,which was a positive correlation,r=0.534,P<0.05(2)Using the Wilcoxon symbolic rank sum test of paired data,there was a significant difference in the level of PRL between the nipple discharge and the corresponding serum.The level of PRL in the nipple discharge was significantly higher than that in the corresponding serum,P<0.054.Analysis of detection level of PRL in colostrum and difference of PRL detection level between nipple discharge and colostrum(1)There was no significant difference in PRL detection level between left and right colostrum specimens of 50 subjects.The average value of PRL detection level in bilateral colostrum samples was normal distribution data,and the mean±standard deviation was 68.80±39.00ng/ml.(2)There was a significant difference in the detection level of PRL between nipple discharge and colostrum samples by two independent samples of Mann-Whitney U test,P<0.05.The level of PRL in nipple discharge was lower than that in colostrum The second part Analysis of serum PRL levels in patients with breast diseases without nipple discharge1.26.32%(35/133)of the benign patients had hyperprolactinemia and 31.25%(45/144)of the malignant patients had hyperprolactinemia.2.There was no significant difference in the incidence of hyperprolactinemia between benign and malignant breast diseases by chi-square test,P>0.05.3.There was no significant difference in the level of PRL in serum samples of benign and malignant breast diseases detected by Mann-Whitney U test from two independent samples,P>0.05。The third part Difference of serum PRL levels between nipple discharge and non-nipple discharge patients with breast disease1.Difference of serum PRL levels in 66 patients with nipple discharge and 277 patients with breast disease without nipple discharge(1)The difference of serum PRL detection level between nipple discharge and non-nipple discharge breast disease patients was compared by two independent samples Mann-Whitney U test.There was significant difference in serum PRL detection level between the two groups,P<0.05,The level of PRL in serum of patients with breast disease with nipple discharge was significantly higher than that without nipple discharge.(2)Chi-square test was used to compare the incidence of hyperprolactinemia in patients with nipple discharge and non-nipple discharge.The results showed that the incidence of hyperprolactinemia in patients with nipple discharge breast disease was significantly higher than that in patients with non-nipple discharge breast disease,P<0.05.2.Difference of serum PRL levels in 14 breast cancer patients with nipple discharge and 144 breast cancer patients without nipple discharge(1)There was no significant difference in serum PRL levels between breast cancer patients with nipple discharge and breast cancer patients without nipple discharge by using two independent samples of Mann-Whitney U test,P>0.05(2)There was no significant difference in the incidence of hyperprolactinemia between breast cancer patients with nipple discharge and breast cancer patients without nipple discharge by chi-square test,P>0.05。3.Difference of serum PRL levels in 52 patients with nipple discharge and 133 patients with benign breast disease without nipple discharge(1)The levels of PRL in serum of patients with benign breast disease with nipple discharge and those without nipple discharge were compared by two independent samples Mann-Whitney U test.There was significant difference in serum PRL level between the two groups,P<0.05.The expression level of PRL in serum with nipple discharge group was significantly higher than that without nipple discharge group(2)Chi-square test was used to compare the incidence of hyperprolactinemia in patients with benign breast diseases between nipple discharge group and non-nipple discharge group.The results showed that the incidence of hyperprolactinemia in nipple discharge group was significantly higher than that in non-nipple discharge group,P<0.05Conclusions1.The level of PRL in nipple discharge is significantly higher than that in serum,suggesting that PRL is locally concentrated in the milk duct,and its specific mechanism needs further experimental study.2.The expression of PRL in nipple discharge and its corresponding serum samples was significantly correlated and positively correlated.PRL in nipple discharge may be affected by serum PRL3.The level of serum PRL in patients with nipple discharge is significantly higher than that in patients with breast disease without nipple discharge,suggesting that PRL may be related to the occurrence of nipple discharge disease4.There was no significant difference in PRL levels between serum and nipple discharge in patients with benign and malignant breast diseases.the role of detecting PRL levels in serum and nipple discharge in differentiating benign and malignant breast diseases needs to be further studied5.There is a high level of PRL,in colostrum and the level of PRL in colostrum is significantly higher than that in nipple discharge,suggesting that PRL may play different roles in physiological and pathological nipple discharge.更多还原