The prognostic value of MARCKS-like 1 in lymph node-negative breast cancer

There is a need for new biomarkers to more correctly identify node-negative breast cancer patients with a good or bad prognosis. Myristoylated alanine-rich C kinase substrate like-1 (MARCKSL1) is a membrane-bound protein that is associated with cell spreading, integrin activation and exocytosis. Three hundred and five operable T1,2N0M0 lymph node-negative breast cancer patients (median follow-up time 121 months, range 10-178 months) were evaluated for MARCKSL1 expression by immunohistochemistry and quantitative real-time PCR. The results were compared with classical prognosticators (age, tumor diameter, grade, estrogen receptor, and proliferation), using single (Kaplan-Meier) and multivariate survival analysis (Cox model). Forty-seven patients (15 %) developed distant metastases. With single and multivariate analysis of all features, MARCKSL1 protein expression was the strongest prognosticator (P < 0.001, HR = 5.1, 95 % CI = 2.7-9.8). Patients with high MARCKSL1 expression (n = 23) showed a 44 % survival versus 88 % in patients with low expression at 15-year follow-up. mRNA expression of MARCKSL1 in formalin fixed paraffin-embedded tissue was also prognostic (P = 0.002, HR = 3.6, 95 % CI = 1.5-8.3). However, the prognostic effect of high and low was opposite from the protein expression, i.e., low expression (relative expression a parts per thousand currency sign 0.0264, n = 76) showed a 79 % survival versus 92 % in those with high expression of MARCKSL1 mRNA. Multivariate analysis of all features with distant metastases free survival as the end-point showed that the combination of MARCKSL1 protein and phosphohistone H3 (PPH3) has the strongest independent prognostic value. Patients with high expression (a parts per thousand yen13) of PPH3 and high MARCKSL1 protein had 45 % survival versus 78 % survival for patients with low MARCKSL1 protein expression and high expression (a parts per thousand yen13) of PPH3. In conclusion, MARCKSL1 has strong prognostic value in lymph node-negative breast cancer patients, especially in those with high proliferation.