Potten C S, Watson R J, Williams G T, Tickle S, Roberts S A, Harris M, Howell A
Department of Epithelial Biology, Paterson Institute for Cancer Research, Manchester, UK.
Br J Cancer. 1988 Aug;58(2):163-70. doi: 10.1038/bjc.1988.185.
The aim of this study was to determine the proliferative activity within the epithelial cells of the normal human breast in 122 patients (6 reduction mammoplasties and 116 fibroadenoma excisions) in relation to age and the phase of the menstrual cycle. Thirty three of the patients were on oral contraceptives and 33 were parous. Thin tissue slices were incubated with tritiated thymidine and processed for autoradiography. Other samples were fixed directly and prepared for histology. The labelling, mitotic and apoptotic indices (LI, MI and AI) were determined and all illustrated considerable variability. The labelling indices are significantly (P less than 0.05) influenced by both patient age and stage during the menstrual cycle and ranged from 0-11.5%. Maximum LI values were obtained on the 20.8th day of the cycle. A square root transformation of the data was used to reduce the skewness of the data to a more normal distribution. The square root of the LI declined by 0.22 per decade. The mitotic data showed similar significant (P less than 0.05) correlations against age and day of cycle with a peak on the 21.5th day of the cycle, a decline by 0.072 per decade and a range from 0-0.6%. The data for apoptotic cells were less clearly influenced by the stage of the menstrual cycle but showed a significant (P less than 0.5) decline with age. The AI in parous patients was significantly higher than that in non-parous patients. There was no significant effect of oral contraceptives on any of the parameters measured when age and stage of cycle were taken into account. The considerable variability in the data could not be fully accounted for by either technical factors, the age of the patients, or the day of the cycle. We conclude that proliferation is negatively related to age and is influenced by the menstrual cycle but that additional as yet unknown factors must account for a large part of the variability seen in the data.
本研究旨在确定122例患者（6例乳房缩小成形术和116例纤维腺瘤切除术）正常人类乳腺上皮细胞内的增殖活性与年龄及月经周期阶段的关系。其中33例患者正在服用口服避孕药，33例已生育。将薄组织切片与氚标记胸腺嘧啶一起孵育并进行放射自显影处理。其他样本直接固定并制备用于组织学检查。测定了标记指数、有丝分裂指数和凋亡指数（LI、MI和AI），结果均显示出相当大的变异性。标记指数受患者年龄和月经周期阶段的显著影响（P小于0.05），范围为0 - 11.5%。在月经周期的第20.8天获得最大LI值。对数据进行平方根变换以将数据的偏度降低到更接近正态分布。LI的平方根每十年下降0.22。有丝分裂数据显示与年龄和月经周期日有类似的显著相关性（P小于0.05），在月经周期的第21.5天达到峰值，每十年下降0.072，范围为0 - 0.6%。凋亡细胞的数据受月经周期阶段的影响不太明显，但随年龄有显著下降（P小于0.5）。已生育患者的AI显著高于未生育患者。在考虑年龄和月经周期阶段时，口服避孕药对所测任何参数均无显著影响。数据中的相当大的变异性不能完全由技术因素、患者年龄或月经周期日来解释。我们得出结论，增殖与年龄呈负相关且受月经周期影响，但其他尚未知晓的因素必定在很大程度上导致了数据中所见的变异性。
