CD44 is prognostic for overall survival in the NCI randomized trial on breast conservation with 25 year follow-up

Abstract

CD44 is a transmembrane glycoprotein involved in numerous cellular functions, including cell adhesion and extracellular matrix interactions. It is known to be functionally diverse, with alternative splice variants increasingly implicated as a marker for tumor-initiating stem cells associated with poor prognosis. Here, we evaluate CD44 as a potential marker of long-term breast cancer outcomes. Tissue specimens from patients treated on the National Cancer Institute 79-C-0111 randomized trial of breast conservation versus mastectomy between 1979 and 1987 were collected, and immunohistochemistry was performed using the standard isoform of CD44. Specimens were correlated with patient characteristics and outcomes. Survival analysis was performed using the log rank test. Fifty-one patients had evaluable tumor sections and available long-term clinical follow up data at a median follow up of 25.7years. Significant predictors of OS were tumor size (median OFS 25.4years for ≤2cm vs. 7.5years for >2cm, p=0.001), nodal status (median OS 17.2years for node-negative patients vs. 6.7years for node positive patients, p=0.017), and CD44 expression (median OS 18.9years for CD44 positive patients vs. 8.6years for CD44 negative patients, p=0.049). There was a trend toward increased PFS for patients with CD44 positive tumors (median PFS 17.9 vs. 4.3years, p=0.17), but this did not reach statistical significance. These findings illustrate the potential utility of CD44 as a prognostic marker for early stage breast cancer. Subgroup analysis in patients with lymph node involvement revealed CD44 positivity to be most strongly associated with increased survival, suggesting a potential role of CD44 in decision making for axillary management. As there is increasing interest in CD44 as a therapeutic target in ongoing clinical trials, the results of this study suggest additional investigation regarding the role CD44 in breast cancer is warranted.