Stroma modifies relationships between risk factor exposure and age-related epithelial involution in benign breast
Stroma modifies relationships between risk factor exposure and age-related epithelial involution in benign breast
复制标题
DOI：
10.1038/s41379-018-0033-7
复制
发表时间：
2018-07-01
期刊：
影响因子：
7.5
通讯作者：
Troester, Melissa A.
中科院分区：
文献类型：
--
作者：
Chollet-Hinton, Lynn;Puvanesarajah, Samantha;Troester, Melissa A.
与年龄相关的小叶退化延迟与乳腺癌风险升高有关。然而，在一个女人的上皮退化状态的个体变异性是不明确的。我们开发了一种新的测量与年龄相关的上皮退化的方法，利用数字图像分析结合基质特征（由基质组成的切片面积的百分比），测量上皮区域中上皮核的密度。大约1800张苏木精和伊红染色的良性乳腺组织切片被评估，这些切片来自416名因癌症或良性疾病接受乳房手术的参与者。研究人员对每位女性乳房不同部位的2到16张载玻片进行了研究。上皮退化的状态在一个女性中是不同的，并作为基质面积的功能。同一女性样本间基质面积百分比不同（同一女性体内基质面积最高和最低的中位数差异为7.5%，但范围从0.01到86.7%）。限于基质面积至少为10%的女性（N = 317），上皮细胞核密度随年龄的增长而下降（40岁后每10年-637.1个细胞/毫米(2),p < 0.0001），随乳房x线摄影密度的增加（每增加BI-RADs密度类别457.8个细胞/毫米(2),p = 0.002），并且随着最近的产次，首次怀孕的年龄较晚，以及较长时间和最近使用口服避孕药而增加。这些相关性在大多数脂肪样本（< 10%基质（N = 99））的女性中减弱。31%的受访女性既有充足的乳腺组织间质区（>= 10%），也有大部分脂肪区（< 10%间质区），这两种类型的可能性都随着乳腺组织采样数量的增加而增加。一些乳腺癌危险因素与年龄相关上皮细胞含量升高有关，但其相关性取决于基质环境。基质特征似乎改变了危险因素暴露与乳腺上皮复旧之间的关系。
Delayed age-related lobular involution has been previously associated with elevated breast cancer risk. However, intraindividual variability in epithelial involution status within a woman is undefined. We developed a novel measure of age-related epithelial involution, density of epithelial nuclei in epithelial areas using digital image analysis in combination with stromal characteristics (percentage of section area comprising stroma). Approximately 1800 hematoxylin and eosin stained sections of benign breast tissue were evaluated from 416 participants having breast surgery for cancer or benign conditions. Two to sixteen slides per woman from different regions of the breast were studied. Epithelial involution status varied within a woman and as a function of stromal area. Percentage stromal area varied between samples from the same woman (median difference between highest and lowest stromal area within a woman was 7.5%, but ranged from 0.01 to 86.7%). Restricting to women with at least 10% stromal area (N = 317), epithelial nuclear density decreased with age (-637.1 cells/mm(2) per decade of life after age 40, p < 0.0001), increased with mammographic density (457.8 cells/mm(2) per increasing BI-RADs density category p = 0.002), and increased non-significantly with recent parity, later age at first pregnancy, and longer and more recent oral contraceptive use. These associations were attenuated in women with mostly fat samples (< 10% stroma (N = 99)). Thirty-one percent of women evaluated had both adequate stroma (>= 10%) and mostly fat (< 10% stroma) regions of breast tissue, with the probability of having both types increasing with the number breast tissue samplings. Several breast cancer risk factors are associated with elevated age-related epithelial content, but associations depend upon stromal context. Stromal characteristics appear to modify relationships between risk factor exposures and breast epithelial involution.