PO.PS01.01 · 人群科学
间质标志物与乳腺终末导管小叶退化的关联
Associations of stromal markers with breast terminal duct lobular involution
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：乳腺癌（BrCa）中间质标志物表达升高已被证明与更具侵袭性的疾病和更差的预后相关。相比之下，关于癌前乳腺组织中间质标志物表达的数据有限，尚不清楚这些标志物是否可用于提示未来乳腺癌风险。终末导管小叶退化（TDLU）是一种以乳腺小叶内TDLU和腺泡数量减少为特征的生理过程，已被证明与较低的乳腺癌风险相关，并被视为乳腺癌的潜在替代风险标志物。在本研究中，我们考察了五种间质标志物与癌前乳腺组织中TDLU退化之间的关联。
设计：对来自护士健康研究（NHS）和NHSII中260名经活检确诊为良性乳腺疾病的无癌女性的组织芯片进行染色，评估α-平滑肌肌动蛋白（αSMA）、成纤维细胞活化蛋白（FAP）、基质金属肽酶（MMP14）、腱生蛋白-C（TNC）和钙周期蛋白（s100A6）。对于每个芯，采用inForm软件量化阳性百分比。我们此前发表的计算算法计算了六项TDLU退化的测量指标，评估TDLU数量（TDLU计数/非脂肪组织面积）、TDLU大小（中位TDLU跨度、中位TDLU面积以及TDLU面积/非脂肪组织面积百分比）和TDLU发育（每个TDLU的中位腺泡计数和中位腺泡密度）。采用广义线性回归考察每种标志物的表达（以1%为界值的二分类变量）与每个特征（对数转换后）之间的关联，并对已确立的乳腺癌风险因素进行校正。
结果：αSMA和MMP14的表达与五项TDLU大小和发育相关特征中的四项呈正相关（均p<0.05）。FAP表达与TDLU大小和发育的三项特征呈正相关：中位TDLU跨度、中位TDLU面积和每个TDLU的中位腺泡计数（均p<0.05）。TNC表达与中位TDLU跨度呈正相关，但与中位腺泡密度和TDLU计数/非脂肪组织面积呈负相关（均p<0.05）。未发现s100A6的关联。
结论：良性乳腺组织中若干间质标志物的表达与更大的TDLU和更多的腺泡相关，即较低程度的小叶退化。相关研究正在进行中，以评估这些发现是否可转化为与乳腺癌风险增加的关联。
查看英文原文 English abstract
Background: Elevated expression of stromal markers in breast cancer (BrCa) has been linked to more aggressive disease and poorer prognosis. In contrast, data on stromal marker expression in premalignant breast tissues are limited, and it remains unclear whether these markers may inform future BrCa risk. Terminal duct lobular involution (TDLU), a physiologic process characterized by a decreased number of TDLUs and acini within breast lobules, has been associated with lower BrCa risk and is considered a potential surrogate risk marker for BrCa. In this study, we examined the associations between five stromal markers and TDLU involution in premalignant breast tissues.
Design: Tissue microarrays from 260 cancer-free women with biopsy-confirmed benign breast disease within the Nurses' Health Study (NHS) and NHSII were stained and evaluated for alpha-smooth muscle actin (alphaSMA), fibroblast activation protein (FAP), matrix metallo-peptidase (MMP14), tenascin-C (TNC), and calcyclin (s100A6). For each core, the % positivity was quantified by the inForm software. Our previously published computational algorithm computed six measures of TDLU involution assessing the number of TDLUs (TDLU counts/non-adipose tissue area), TDLU size (median TDLU span, median TDLU area, and TDLU area/% of non-adipose tissue area), and TDLU development (median acini counts/TDLU and median acini density). The associations of each marker's expression (binary with 1% cut-off) with each feature (log-transformed) was examined using generalized linear regression, adjusting for established BCa risk factors.
Results: The expression of alphaSMA and MMP14 was positively associated with four out of five features related to TDLU size and development (all p <0.05). FAP expression was positively associated with three features of TDLU size and development: median TDLU span, median TDLU area, and median acini counts/TDLU (all p <0.05). TNC expression was positively associated with median TDLU span but inversely associated with median acini density and TDLU counts/non-adipose tissue area (all p <0.05). No associations were found for s1006a.
Conclusions: The expression of several stromal markers in benign breast tissue was associated with larger TDLUs and more acini, i.e., lower degrees of lobular involution. Studies are underway to evaluate if these findings translate into associations with increased BCa risk.
利益披露 Disclosure
Y. D. Guzman-Arocho, None..
L. Yaghjyan, None..
L. C. Collins, None..
B. R. Sardella, None..
M. Ratcliffe, None..
R. M. Tamimi, None..
Y. J. Heng, None.