FAP-a and GOLPH3 Are Hallmarks of DCIS Progression to Invasive Breast Cancer.

Li-Na Yu,Zhen Liu,Pei-Pei Zhao,Xing Hua,Yan Tian

doi:10.3389/fonc.2019.01424

Abstract

Biological markers that could predict the progression of ductal carcinoma in-situ (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.

Highlights

With the development and aid of high quality screening mammography, the probability of detected ductal carcinoma in situ (DCIS) has raised rapidly [1]
ductal carcinoma in-situ (DCIS) is considered as a precursor to invasive breast cancer
We demonstrated that 24.50% of DCIS patients undergo an ipsilateral local recurrence, and 13.59% of these recurrences are invasive in a sample of 449 DCIS patients

Summary

Introduction

With the development and aid of high quality screening mammography, the probability of detected ductal carcinoma in situ (DCIS) has raised rapidly [1]. DCIS declares roughly 20% of all screening-detected breast cancer recently [2]. DCIS remains the status of the carcinoma precursor lesion of invasive ductal carcinoma (IDC), but mechanisms under the conversion are largely unknown [5,6,7]. In order to predict the fate of DCIS more accurately, to develop invasive cancer or remain at DCIS status, efforts must be made continuously to investigate the molecular aspects of the disease. Suppression of Cav-1 and activation of MCT4 in the stroma were indicators of overproduction of oxidative stress and glycolysis, indicating the progression from DCIS status into IDC

Methods

Results

Conclusion