Abstract
BackgroundMenacalc is an immunofluorescence-based, quantitative method in which expression of the non-invasive Mena protein isoform (Mena11a) is subtracted from total Mena protein expression. Previous work has found a significant positive association between Menacalc and risk of death from breast cancer. Our goal was to determine if Menacalc could be used as an independent prognostic marker for axillary node-negative (ANN) breast cancer.MethodsAnalysis of the association of Menacalc with overall survival (death from any cause) was performed for 403 ANN tumors using Kaplan Meier survival curves and the univariate Cox proportional hazards (PH) model with the log-rank or the likelihood ratio test. Cox PH models were used to estimate hazard ratios (HRs) for the association of Menacalc with risk of death after adjustment for HER2 status and clinicopathological tumor features.ResultsHigh Menacalc was associated with increased risk of death from any cause (P = 0.0199, HR (CI) = 2.18 (1.19, 4.00)). A similarly elevated risk of death was found in the subset of the Menacalc cohort which did not receive hormone or chemotherapy (n = 142) (P = 0.0052, HR (CI) = 3.80 (1.58, 9.97)). There was a trend toward increased risk of death with relatively high Menacalc in the HER2, basal and luminal molecular subtypes.ConclusionsMenacalc may serve as an independent prognostic biomarker for the ANN breast cancer patient population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1468-6) contains supplementary material, which is available to authorized users.
Highlights
Menacalc is an immunofluorescence-based, quantitative method in which expression of the noninvasive Mena protein isoform (Mena11a) is subtracted from total Mena protein expression
Patients were excluded from recruitment into this axillary node-negative (ANN) cohort if (1) No tumor specimen was provided for analysis, (2) no axillary dissection was performed as part of surgical management, (3) less than four lymph nodes were biopsied and analyzed, (4) pathology revealed that the patient was diagnosed with carcinoma-in-situ disease, (5) the patient had distant metastases at the time of diagnosis, (6) the patient had synchronous primary breast tumors, (7) the patient had a previous breast malignancy, and (8) the patient had a secondary malignancy other than non-melanoma of the skin and carcinoma-insitu of the cervix
Of the 54 recurrences observed, 15 patients presented with bone metastases alone, 14 patients presented with chest wall or regional lymph node involvement, 8 patients presented with lung metastases alone, 2 patients presented with liver metastases alone, 1 patient presented with skin metastases alone and 1 patient presented with a solitary neck muscle deposit. 8 patients presented with bone and liver metastases and 3 patients presented with bone and lung metastases. 2 patients presented with widespread multi-organ involvement
Summary
Menacalc is an immunofluorescence-based, quantitative method in which expression of the noninvasive Mena protein isoform (Mena11a) is subtracted from total Mena protein expression. Mena is a pro-motility protein that is a member of the Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) family of actin polymerization regulators [7] It controls the geometry of assembling F-actin networks by antagonizing the activity of capping proteins at elongating actin filaments [8]. Forse et al BMC Cancer (2015) 15:483 shown to have an important role in breast cancer metastasis in both in vitro and in vivo experimental models [12]. It is an essential member of the Invasion Signature, a collection of transiently expressed proteins that control chemotactic and migratory behavior in primary rat, mouse and human mammary tumors [13,14,15,16]. In mouse models of breast cancer, forced overexpression of Mena increased lung metastases [17,18,19,20], while Mena deficiency decreased tumor burden by delaying tumor invasion, intravasation and dissemination to the lungs [20]
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