Matches in SemOpenAlex for { <https://semopenalex.org/work/W4246139430> ?p ?o ?g. }
- W4246139430 endingPage "27" @default.
- W4246139430 startingPage "1" @default.
- W4246139430 abstract "Conjunctival malignant melanoma is a rare disease associated with considerable mortality. Most published data have been based on case reports or series of referred patients. In addition, very little is known about the genetic and epigenetic profile of conjunctival melanoma and the resemblance to uveal, cutaneous and mucosal melanoma. The aim was to determine the incidence rate of conjunctival melanoma, and to relate clinicopathological features and treatment to prognosis. A further aim was to determine the prevalence of BRAF mutations in conjunctival melanoma, to determine whether BRAF mutations are early events in pathogenesis, and relate clinicopathological features and prognosis to BRAF-mutation status. Finally, we wanted to identify tumour-specific and prognostic microRNAs in conjunctival melanoma, and to compare these with the microRNA expression of other melanoma subtypes. In order to investigate these rare tumours, we studied all the conjunctival melanomas that had been surgically removed in Denmark over a period of 52 years (1960-2012). Tissue samples, clinical files, pathology reports and follow-up data were collected and re-evaluated. Using droplet digital polymerase chain reaction and immunohistochemistry, we investigated BRAF mutations; and using microRNA expression profiling, we investigated differentially expressed microRNAs. The overall incidence of conjunctival melanoma was 0.5/1 000 000/year, and it increased in Denmark over 52 years. The increase was mainly caused by an increase in older patients (>65 years) and bulbar lesions. Clinicopathological features significantly associated with a poor prognosis were extrabulbar location, involvement of adjacent tissue structures, tumour thickness exceeding 2 mm and local tumour recurrence. Patients undergoing incisional biopsy and/or treatment involving excision without adjuvant therapy fared worse than patients treated with excision and any type of adjuvant treatment. We found that 35% (39/110) of conjunctival melanomas were BRAF-mutated, and the incidence of BRAF mutations was constant over time. BRAF-mutation status corresponded in conjunctival melanoma and paired premalignant lesions. BRAF mutations were more frequent in males, in young patients, and in tumours with a sun-exposed tumour location (bulbar conjunctiva or caruncle), with a mixed or non-pigmented colour, with absence of primary acquired melanosis, and with origin in a nevus. Immunohistochemistry was able to accurately detect BRAF V600E mutations. In univariate analysis, distant metastatic disease was associated with BRAF mutations. No prognostic associations with BRAF mutations were identified in multivariate analyses. MicroRNA expression analysis revealed 25 tumour-specific microRNAs in conjunctival melanoma. Five possibly oncogenic miRNAs (miR-20b-5p, miR-146b-5p, miR-146a-5p, miR-506-3p and miR-509-3p) were up-regulated. Seven microRNAs (miR-30d-5p, miR-138-5p, miR-146a-5p, miR-500a-5p, miR-501-3p, miR-501-5p and miR-502-3p) were significantly and simultaneously up-regulated in both stage T1 and stage T2 tumours, and were associated with increased tumour thickness. The expression of the 25 tumour-specific microRNAs did not differ significantly between conjunctival melanoma and oral or nasal mucosal melanoma. In conclusion, the incidence of conjunctival melanoma increased in the Danish population from 1960 to 2012. From our findings of a distinct pattern of BRAF mutations and differentially expressed microRNAs, it is evident that conjunctival melanoma is closely related to cutaneous and other mucosal melanomas and bears less resemblance to uveal melanomas. This means that conjunctival melanoma patients may benefit from therapies that are effective for cutaneous and mucosal melanoma. Additionally, the identification of several up-regulated microRNAs may prove to be useful as prognostic or therapeutic targets in conjunctival melanoma." @default.
- W4246139430 created "2022-05-12" @default.
- W4246139430 creator A5023770398 @default.
- W4246139430 date "2016-05-01" @default.
- W4246139430 modified "2023-10-16" @default.
- W4246139430 title "Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile" @default.
- W4246139430 cites W1545177819 @default.
- W4246139430 cites W158671797 @default.
- W4246139430 cites W1591345781 @default.
- W4246139430 cites W1648301895 @default.
- W4246139430 cites W173252383 @default.
- W4246139430 cites W188457887 @default.
- W4246139430 cites W1953473874 @default.
- W4246139430 cites W1963812825 @default.
- W4246139430 cites W1964493174 @default.
- W4246139430 cites W1965171040 @default.
- W4246139430 cites W1965537221 @default.
- W4246139430 cites W1966990300 @default.
- W4246139430 cites W1968690480 @default.
- W4246139430 cites W1970332531 @default.
- W4246139430 cites W1970977508 @default.
- W4246139430 cites W1971174454 @default.
- W4246139430 cites W1972375868 @default.
- W4246139430 cites W1972972601 @default.
- W4246139430 cites W1976587524 @default.
- W4246139430 cites W1977995175 @default.
- W4246139430 cites W1979910583 @default.
- W4246139430 cites W1980691287 @default.
- W4246139430 cites W1984776107 @default.
- W4246139430 cites W1985309655 @default.
- W4246139430 cites W1986812000 @default.
- W4246139430 cites W1986949331 @default.
- W4246139430 cites W1988973245 @default.
- W4246139430 cites W1989677596 @default.
- W4246139430 cites W1992839523 @default.
- W4246139430 cites W1996429288 @default.
- W4246139430 cites W1997283765 @default.
- W4246139430 cites W1997527307 @default.
- W4246139430 cites W1998380666 @default.
- W4246139430 cites W1998946924 @default.
- W4246139430 cites W2001063465 @default.
- W4246139430 cites W2002420654 @default.
- W4246139430 cites W2003650710 @default.
- W4246139430 cites W2004456224 @default.
- W4246139430 cites W2004473768 @default.
- W4246139430 cites W2006985176 @default.
- W4246139430 cites W2013443950 @default.
- W4246139430 cites W2016356201 @default.
- W4246139430 cites W2017373068 @default.
- W4246139430 cites W2017403445 @default.
- W4246139430 cites W2021012420 @default.
- W4246139430 cites W2022143863 @default.
- W4246139430 cites W2022660749 @default.
- W4246139430 cites W2022763768 @default.
- W4246139430 cites W2025726731 @default.
- W4246139430 cites W2026145190 @default.
- W4246139430 cites W2027384688 @default.
- W4246139430 cites W2027482633 @default.
- W4246139430 cites W2029155466 @default.
- W4246139430 cites W2029761866 @default.
- W4246139430 cites W2030684277 @default.
- W4246139430 cites W2031045499 @default.
- W4246139430 cites W2033993004 @default.
- W4246139430 cites W2034375896 @default.
- W4246139430 cites W2035275245 @default.
- W4246139430 cites W2036576441 @default.
- W4246139430 cites W2036842896 @default.
- W4246139430 cites W2040584053 @default.
- W4246139430 cites W2042913575 @default.
- W4246139430 cites W2043632581 @default.
- W4246139430 cites W2046861616 @default.
- W4246139430 cites W2047539255 @default.
- W4246139430 cites W2047570552 @default.
- W4246139430 cites W2048618556 @default.
- W4246139430 cites W2050109467 @default.
- W4246139430 cites W2050794661 @default.
- W4246139430 cites W2051144764 @default.
- W4246139430 cites W2051221156 @default.
- W4246139430 cites W2051620527 @default.
- W4246139430 cites W2053102358 @default.
- W4246139430 cites W2053520756 @default.
- W4246139430 cites W2053757597 @default.
- W4246139430 cites W2058122994 @default.
- W4246139430 cites W2058321871 @default.
- W4246139430 cites W2060573548 @default.
- W4246139430 cites W2066868471 @default.
- W4246139430 cites W2068054722 @default.
- W4246139430 cites W2070443005 @default.
- W4246139430 cites W2070479805 @default.
- W4246139430 cites W2070871778 @default.
- W4246139430 cites W2073010687 @default.
- W4246139430 cites W2074283639 @default.
- W4246139430 cites W2077561068 @default.
- W4246139430 cites W2081062769 @default.
- W4246139430 cites W2081098333 @default.
- W4246139430 cites W2081936027 @default.
- W4246139430 cites W2083372198 @default.
- W4246139430 cites W2086529225 @default.