Measurement of human epidermal growth factor receptor type-2 extracellular domain and cancer antigen 15–3 levels in needle washout fluid: a potential adjunct to the cytological diagnosis of breast cancer

Abstract

To determine whether the measurement of biomarkers in the needle washout fluid after fine needle aspiration cytology could strengthen cytological diagnosis, 29 benign lesions, 26 ductal carcinomas in situ (DCIS), and 95 invasive carcinomas of the breast were analyzed. Immediately after the aspiration samples were expelled onto glass slides, the needle was rinsed out with 2 ml of saline. Human epidermal growth factor receptor two extracellular domain (HER2-ECD) and cancer antigen 15-3 (CA 15-3) in the washout fluid were measured using chemiluminescence. The measuring limit for HER2-ECD (0.5 ng/ml) and that for CA 15-3 (4 U/ml) were used as the cutoff values, respectively. The proportion of patients with positive HER2-ECD values was 6.9% in cases of benign lesions, 26.9% in DCIS, and 10.5% in invasive carcinomas. The proportion of patients with positive CA 15-3 values was 6.9% in cases of benign lesions, 42.3% in DCIS, and 10.5% in invasive carcinomas. The proportion of patients with any biomarker elevation was 6.9% in cases of benign lesions, 46.2% in DCIS, and 15.8% in invasive carcinomas. Thus, biomarker elevation was most frequent in cases of DCIS, followed by invasive carcinomas (P < 0.01). HER2-ECD values over 6 ng/ml or CA 15-3 values over 25 U/ml were seen exclusively in cases of DCIS or invasive ductal carcinomas with an extensive intraductal component. If the biomarker status is included, 5 of 12 cases of DCIS with equivocal cytology categories would be upgraded. Further clinicopathological validation is necessary before applying this new approach to the clinical setting.

CA153 in Breast Secretions as a Potential Molecular Marker for Diagnosing Breast Cancer: A Meta Analysis

“…First of all, CA153 in BS could be a promising biomarker for the diagnosis of early BC. Although relevant studies are so few that the diagnostic role of BS CA153 for BC cannot supported by a meta-analysis, two studies demonstrated CA153 in BS can discriminate early BC from healthy controls, indicating its diagnostic value for early-stage BC [ 10 , 14 ]. Second, the detection of CA153 in BS is safe and accessible.…”

“…In theory, the higher the stage of breast cancer, the higher the CA153 concentration in breast secretions; the levels of CA153 in breast secretions would be significantly decreased after accepting effective treatments. One of the 5 primary studies showed an opposite result that the levels of CA153 in breast secretions from invasive breast cancer are lower than that from DCIS [ 10 ], which might result from the blockage of breast ducts during the breast cancer expansion. However, whether the levels of CA153 in breast secretions respond to any clinical treatment has not been reported.…”

“…Many studies have shown that BS could facilitate the diagnosis of early BC. BS, being secreted from the ductal and lobular epithelium of breast, contains higher concentrated proteins than serum and is only located in the ductal lumen in normal pathological conditions [ 10 ]. Under conditions of BC, excessive BS from the ductal lumen can be presented in various forms such as nipple discharge, effusions, and washout fluid [ 7 ].…”

“…Excessive BS is a common complaint of breast patients and reflects the breast microenvironment [ 11 ]. Compared with normal pathological conditions, specific components accumulate in the basement membrane-bound space of intraductal carcinoma until the continuity of the basement membrane is lost during stromal invasion [ 10 ]. Thus, many BS-based indexes were developed to improve the diagnosis of BC, especially early BC.…”

“…Subsequently, it was first reported that CA153 in BS can differentiate malignant breast cancers from benign breast diseases and is a more valuable biomarker for diagnosing BC compared with mammography [ 14 ]. Later,many researchers also investigated the diagnostic role of CA153 in BS [ 10 , 15 – 17 ].…”