Franco Renato, Collina Francesca, Di Bonito Maurizio, Botti Gerardo, Montanaro Donatella, Di Maio Luigi, Vincenzi Bruno, Landi Gabriella, D'Aiuto Massimiliano, Caraglia Michele, Baldi Alfonso
Pathology Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy.
CEINGE, Biotecnologie Avanzate, Naples, Italy.
Histol Histopathol. 2015 Jun;30(6):707-14. doi: 10.14670/HH-30.707. Epub 2014 Dec 22.
HtrA1, a member of the High Temperature Requirement Factor A family of oxidative stress-response proteases seems to play a role as a tumor suppressor, being down-regulated in a series of human cancers during their progression. Particularly, low HtrA1 mRNA levels have been observed in breast cancer patients with more aggressive clinical features. These have been shown to relate to a longer disease free and overall survival, with more pronounced effects in axillary nodes positive patients.
We have analyzed for immunohistochemical HtrA1 expression a series of 66 sentinel node positive breast cancers through Tissue Micro Array technology.
HtrA1 was absent to low in 29 cases, medium in 19 cases and high in 18 cases. Our data revealed a positive significant relation between HtrA1 expression level and estrogen (p=0,002) and progestinic receptor expression (p=0.003) and a negative correlation with histological grading (p=0.028), proliferation index (p=0.05), common BC histotypes (p=0.040), luminal A and B subtypes (p=0.001), metastasis development (p<0.0001) and local relapse (p<0.0001). Finally, no correlation was recorded between HtrA1 expression level and breast cancer histology type and metastasis to non sentinel nodes. Interestingly HtrA1 loss in SLN metastasis was able to predict positive non sentinel nodes (p=0.001).
Low HtrA1 expression is significantly related to breast cancer poor prognosis parameters, and HtrA1 loss in sentinel nodes is related to metastasis of non sentinel nodes, offering a further marker useful for BC prognostic stratification.
HtrA1是高温需求因子A家族氧化应激反应蛋白酶的成员之一，似乎起着肿瘤抑制作用，在一系列人类癌症进展过程中表达下调。特别是，在具有更具侵袭性临床特征的乳腺癌患者中观察到HtrA1 mRNA水平较低。这些已被证明与更长的无病生存期和总生存期相关，对腋窝淋巴结阳性患者的影响更为明显。
我们通过组织微阵列技术对66例前哨淋巴结阳性乳腺癌进行了免疫组化HtrA1表达分析。
29例HtrA1表达缺失至低水平，19例为中等水平，18例为高水平。我们的数据显示HtrA1表达水平与雌激素（p = 0.002）和孕激素受体表达（p = 0.003）呈正相关，与组织学分级（p = 0.028）、增殖指数（p = 0.05）、常见乳腺癌组织学类型（p = 0.040）、管腔A和B亚型（p = 0.001）、转移发展（p < 0.0001）和局部复发（p < 0.0001）呈负相关。最后，未记录到HtrA1表达水平与乳腺癌组织学类型及非前哨淋巴结转移之间的相关性。有趣的是，前哨淋巴结转移中HtrA1缺失能够预测非前哨淋巴结阳性（p = 0.001）。
低HtrA1表达与乳腺癌不良预后参数显著相关，前哨淋巴结中HtrA1缺失与非前哨淋巴结转移相关，为乳腺癌预后分层提供了另一个有用的标志物。
