Cytoplasmic BRMS1 expression in malignant melanoma is associated with increased disease-free survival
AuthorSlipicevic, Ana; Holm, Ruth; Emilsen, Elisabeth; Rosnes, Anne Katrine Ree; Welch, Danny R.; Mælandsmo, Gunhild; Flørenes, Vivi Ann
Breast cancer metastasis suppressor 1 (BRMS1) blocks metastasis in melanoma xenografts; however, its usefulness as a biomarker in human melanomas has not been widely studied. The goal was to measure BRMS1 expression in benign nevi, primary and metastatic melanomas and evaluate its impact on disease progression and prognosis. Paraffin-embedded tissue from 155 primary melanomas, 69 metastases and 15 nevi was examined for BRMS1 expression using immunohistochemistry. siRNA mediated BRMS1 down-regulation was used to study impact on invasion and migration in melanoma cell lines. A significantly higher percentage of nevi (87%), compared to primary melanomas (20%) and metastases (48%), expressed BRMS1 in the nucelus (p < 0.0001). Strong nuclear staining intensity was observed in 67% of nevi, and in 9% and 24% of the primary and metastatic melanomas, respectively (p < 0.0001). Comparable cytoplasmic expression was observed (nevi; 87%, primaries; 86%, metastases; 72%). However, a decline in cytoplasmic staining intensity was observed in metastases compared to nevi and primary tumors (26%, 47%, and 58%, respectively, p < 0.0001). Score index (percentage immunopositive celles multiplied with staining intensity) revealed that high cytoplasmic score index (≥ 4) was associated with thinner tumors (p = 0.04), lack of ulceration (p = 0.02) and increased disease-free survival (p = 0.036). When intensity and percentage BRMS1 positive cells were analyzed separately, intensity remained associated with tumor thickness (p = 0.024) and ulceration (p = 0.004) but was inversely associated with expression of proliferation markers (cyclin D3 (p = 0.008), cyclin A (p = 0.007), and p21Waf1/Cip1 (p = 0.009)). Cytoplasmic score index was inversely associated with nuclear p-Akt (p = 0.013) and positively associated with cytoplasmic p-ERK1/2 expression (p = 0.033). Nuclear BRMS1 expression in ≥ 10% of primary melanoma cells was associated with thicker tumors (p = 0.016) and decreased relapse-free period (p = 0.043). Nuclear BRMS1 was associated with expression of fatty acid binding protein 7 (FABP7; p = 0.011), a marker of invasion in melanomas. In line with this, repression of BRMS1 expression reduced the ability of melanoma cells to migrate and invade in vitro. Our data suggest that BRMS1 is localized in cytoplasm and nucleus of melanocytic cells and that cellular localization determines its in vivo effect. We hypothesize that cytoplasmic BRMS1 restricts melanoma progression while nuclear BRMS1 possibly promotes melanoma cell invasion.
CitationBMC Cancer (2012) 12:73
The following license file are associated with this item:
Showing items related by title, author, creator and subject.
Prognostic Impacts of Angiopoietins in NSCLC Tumor Cells and Stroma : VEGF-A Impact Is Strongly Associated with Ang-2 Andersen, Sigve; Dønnem, Tom; Al-Shibli, Khalid Ibrahim; Al-Saad, Samer; Stenvold, Helge; Busund, Lill-Tove; Bremnes, Roy M. (Journal article; Tidsskriftartikkel; Peer reviewed, 2011)Angiopoietins and their receptor Tie-2 are, in concert with VEGF-A, key mediators in angiogenesis. This study evaluates the prognostic impact of all known human angiopoietins (Ang-1, Ang-2 and Ang-4) and their receptor Tie-2, as well as their relation to the prognostic expression of VEGF-A. 335 unselected stage I-IIIA NSCLC-patients were included and tissue samples of respective tumor cells and ...
Humant papillomavirus : en litteraturstudie om HPV, dets relasjon til cancer og tiltak mot videre spredning av virus Gabrielsen, Endre (Master thesis; Mastergradsoppgave, 2012-06-01)I 1983 oppdaget zur Hausen sammenhengen mellom Humant Papillomavirus (HPV) og livmorhalskreft. På denne tiden visste man ikke at det var HPV som var årsaken til at Helaceller kunne leve in vitro. Ny forskning relaterer HPV til en rekke andre cancertyper. En stor andel anal-, oropharyngeal-, penis-, vaginal-, og vulvacancer skyldes HPV. Det er også påvist HPV i tumorvev fra øsofagus, larynx, lunge, ...
Hoem, Gry (Master thesis; Mastergradsoppgave, 2012-06)Fragile X syndrome (FXS) is caused by an expanded CGG repeat (>200 repeats) in the 5’ un-translated portion of the fragile mental retardation 1 gene (FMR1) leading to deficiency or absence of the FMR1 protein (FMRP). FMRP is an RNA carrier protein that controls the translation of a number of other genes that regulate synaptic development and plasticity. Autism occurs in approximately 30% of FXS ...