Yu Li-Na, Liu Zhen, Tian Yan, Zhao Pei-Pei, Hua Xing
Department of Pathology, Nanfang Hospital, Guangzhou, China.
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Front Oncol. 2019 Dec 17;9:1424. doi: 10.3389/fonc.2019.01424. eCollection 2019.
Biological markers that could predict the progression of ductal carcinoma (DCIS) to invasive breast cancer (IDC) are required urgently for personalized therapy for patients diagnosed with DCIS. As stroma was invaded by malignant cells, perturbed stromal-epithelial interactions would bring about tissue remodeling. With the specific expression of the fibroblast activation protein-alpha (FAP-a), Carcinoma-associated fibroblasts (CAFs) are the main cell populations in the remodeled tumor stroma. Golgi phosphoprotein 3 (GOLPH3), a documented oncogene possessing potent transforming capacity, is not only up-regulated in many tumors but also an efficient indicator of poor prognosis and more malignant tumors. The present study aimed to retrospectively evaluate the pathological value of FAP-a and GOLPH3 in predicting the recurrence or progression of DCIS to invasive breast cancer. Immunohistochemical techniques were applied to investigate the expression of FAP-a GOLPH3 in 449 cases of DCIS patients received extensive resection and with close follow-up, but not being treated with any form of chemo- or radio-therapy. The combination of FAP-a and GOLPH3 in predicating the recurrence or progression of DCIS into invasive breast cancer was specifically examined. The study demonstrated that the overexpression of FAP-a in stromal fibroblasts and GOLPH3 in carcinoma cells are highly predictive of DCIS recurrence and progression into invasive breast cancer. Both FAP-a and GOLPH3 have high specificity and sensitivity to predict the recurrence of DCIS. Moreover, the combination of FAP-a and GOLPH3 tends to further improve the specificity and sensitivity of DCIS recurrence by 9.72-10.31 and 2.72-3.63%, respectively. FAP-a and GOLPH3 serve as novel markers in predicting the recurrence or progression of DCIS into invasive breast cancer.
对于被诊断为导管原位癌（DCIS）的患者进行个性化治疗，迫切需要能够预测DCIS进展为浸润性乳腺癌（IDC）的生物标志物。随着基质被恶性细胞侵袭，基质-上皮相互作用紊乱会导致组织重塑。癌相关成纤维细胞（CAFs）是重塑肿瘤基质中的主要细胞群体，其特异性表达成纤维细胞活化蛋白-α（FAP-α）。高尔基体磷蛋白3（GOLPH3）是一种已被证实具有强大转化能力的致癌基因，不仅在许多肿瘤中上调，还是预后不良和肿瘤更具侵袭性的有效指标。本研究旨在回顾性评估FAP-α和GOLPH3在预测DCIS复发或进展为浸润性乳腺癌方面的病理价值。应用免疫组织化学技术研究449例接受广泛切除且密切随访、未接受任何形式化疗或放疗的DCIS患者中FAP-α和GOLPH3的表达情况。特别检测了FAP-α和GOLPH3联合预测DCIS进展为浸润性乳腺癌的情况。研究表明，基质成纤维细胞中FAP-α的过表达和癌细胞中GOLPH3的过表达高度预测DCIS复发及进展为浸润性乳腺癌。FAP-α和GOLPH3在预测DCIS复发方面均具有高特异性和敏感性。此外，FAP-α和GOLPH3联合使用往往分别进一步提高DCIS复发预测的特异性和敏感性9.72 - 10.31%和2.72 - 3.63%。FAP-α和GOLPH3可作为预测DCIS进展为浸润性乳腺癌复发或进展的新型标志物。
