title: The prognostic value of MARCKS-like 1 in lymph node-negative breast cancer.
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.
authors: Department of Pathology, Stavanger University Hospital, PO Box 8100, 4068 Stavanger, Norway.
authors: Kristin
authors: K
authors: Jonsdottir
authors: Hui
authors: H
authors: Zhang
authors: Darshni
authors: D
authors: Jhagroe
authors: Ivar
authors: I
authors: Skaland
authors: Aida
authors: A
authors: Slewa
authors: Benny
authors: B
authors: Björkblom
authors: Eleanor T
authors: ET
authors: Coffey
authors: Einar
authors: E
authors: Gudlaugsson
authors: Rune
authors: R
authors: Smaaland
authors: Emiel A M
authors: EA
authors: Janssen
authors: Jan P A
authors: JP
authors: Baak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002148:Calmodulin-Binding Proteins; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D006657:Histones / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D053531:Keratins, Type II / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D002148:Calmodulin-Binding Proteins; D006657:Histones; D053531:Keratins, Type II; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D008840:Microfilament Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C070177:MARCKSL1 protein, human; C508053:ERBB2 protein, human