Mammaglobin Expression in Leukapheresis Products Is a Predictive Marker of Poor Prognosis in Women with High-Risk Breast Cancer

Abstract

Purpose: The purpose of this study was to investigate the incidence and prognostic relevance of tumor cell detection in granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cell collections (PBPCCs) using cytokeratin (CK), maspin (MAS), and mammaglobin (MAM) genes as epithelial cell markers. The population on which the study was conducted was drawn from stage III breast cancer patients undergoing high-dose chemotherapy and autologous transplantation with PBPCCs.Experimental Design: One hundred and ninety-four patients were enrolled in the study and analyzed for tumor cell detection on the basis of 481 PBPCCs gathered before administration of chemotherapy. CK, MAS, and MAM gene expressions were investigated by means of the reverse transcription nested polymerase chain reaction, and those samples expressing CK were further hybridized with a radiolabeled internal probe to reduce false-positive results. Sensitivity and specificity were assessed on 37 controls (12 cell lines, 12 healthy donors, and 13 nonepithelial malignancies). Each of the known prognostic variables (age, stage, lymph node status, receptor status, c-ErbB2 status, and Ki67 status) was then analyzed (both individually and together with CK, MAS, and MAM expression on PBPCCs) in relation to patient overall survival (OS) and relapse-free survival (RFS).Results: After a 3-year follow-up, an estimated 83% (95% confidence interval, 77.1-88.8%) of the patients were alive and an estimated 67% (95% confidence interval, 60.1-74.6%) were free of relapse. One hundred and seventy-six of the 194 patients (91%) had contaminated PBPCCs evidenced by at least one positive sample for any of the markers evaluated. The PBPCC frequency of CK, MAS, and MAM positivity (؉) was 71%, 36%, and 16%, respectively. MAM expression on PBPCC was associated with an increased risk of relapse (P ‫؍‬ 0.003), whereas CK and MAS expressions were not associated with changes in either RFS or OS.Conclusions: MAM gene expression on leukapheresis products of high-risk breast cancer patients is an indicator of poor prognosis. The method of evaluation is simple and reproducible and provides new tools for evaluating the role played by tumor cells in apheresis products and their potential in causing metastasis.

Prognostic role of plasma mammaglobin A expression in breast carcinoma patients: a meta-analysis

“…Initially, 260 articles were identified using our search strategy. According to inclusion and exclusion criteria, a total of 20 articles 15 , 17 – 20 , 23 – 37 involving 2,323 breast carcinoma patients were included in the meta-analysis ( Figure 1 ). Detailed characteristics of the included studies are summarized in Table 1 : the publication years ranged from 2000 to 2016, and the number of patients in each study ranged from 48 to 321.…”

Tumor Cell Purging by Ex Vivo Expansion of Hemopoietic Stem Cells from Breast Cancer Patients Combined with Targeting ErbB Receptors

“…The clinical benefit of high-dose chemotherapy programs with autologous stem cell transplantation for the treatment of metastatic breast cancer is a matter of discussion [1,2]. Studies on the prognostic significance of occult tumor cell contamination in apheresis products show contradictory results and are still not conclusive [3][4][5][6][7][8][9][10].…”

“…In this work, we set up a small-scale culture system of MPB from breast cancer patients to obtain the expansion of hemopoietic progenitors and the selective elimination of contaminating tumor cells by targeting ErbB receptors. Because mammaglobin (MAM) is the most specific marker for the detection of epithelial cell contamination in hematologic samples [10,30], we used MAM messenger RNA (mRNA) amplification by quantitative polymerase chain reaction (PCR) to monitor tumor contamination before and after culture.…”