The prognostic value of MARCKS-like 1 in lymph node-negative breast cancer |
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Authors: | Kristin Jonsdottir Hui Zhang Darshni Jhagroe Ivar Skaland Aida Slewa Benny Bj?rkblom Eleanor T. Coffey Einar Gudlaugsson Rune Smaaland Emiel A. M. Janssen Jan P. A. Baak |
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Affiliation: | Department of Pathology, Stavanger University Hospital, P.O. Box 8100, 4068, Stavanger, Norway. |
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Abstract: | 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 T(1,2)N(0)M(0) 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?≤?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 (≥13) of PPH3 and high MARCKSL1 protein had 45?% survival versus 78?% survival for patients with low MARCKSL1 protein expression and high expression (≥13) of PPH3. In conclusion, MARCKSL1 has strong prognostic value in lymph node-negative breast cancer patients, especially in those with high proliferation. |
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