Analysis of PRAME immunocytochemistry in 109 acral malignant melanoma in situ.

AIMS: Preferentially expressed antigen in melanoma (PRAME) recently is a reliable immunohistochemistry (IHC) marker for distinguishing melanoma from other lesions. However, there are few articles focused on PRAME use in acral malignant melanoma, the most common type in Asians. This study investigated PRAME IHC expression in a large series of acral malignant melanoma in situ to add to the body of clinical knowledge. METHODS: PRAME IHC was performed in unequivocal cases of primary acral lentiginous melanoma in situ (ALMIS), subungual melanoma in situ (SMIS) and acral recurrent nevi as the control. PRAME tumour cell percentage positivity and intensity were expressed as categorised in a cumulative score by adding the quartile of positive tumour cells to intensity labelling. The final IHC expression was interpreted as negative (0-1), weak (2-3), moderate (4-5) or strong (6-7). RESULTS: In 91 ALMIS patients, 32 cases (35.16%) were strong, 37 (40.66%) were moderate and 22 (24.18%) were weak. In 18 SMIS patients, strong positivity of PRAME was observed in 4 (22.22%) cases, moderate in 10 (55.56%) and weak in the remaining 4 (22.22%). No melanoma sample was negative for PRAME. By comparison, only 2 of the 40 acral recurrent nevi cases were positive. CONCLUSIONS: Our study supports the ancillary value of PRAME for diagnosing ALMIS and SMIS with high sensitivity and specificity.

Ovostatin 2 knockdown significantly inhibits the growth, migration, and tumorigenicity of cutaneous malignant melanoma cells.

BACKGROUND: We previously identified ovostatin 2 (OVOS2) as a new candidate gene for cutaneous malignant melanoma (CMM) in a Chinese population. In this study, we aimed to investigate the exact role of OVOS2 in cell proliferation, invasion, and tumorigenesis of melanoma A375 cells. METHODS: The downregulation of OVOS2 expression was performed using lentiviral vectors with specific shRNA. The effects of OVOS2 expression on cell proliferation, cell cycle, cell migration, cell invasion, and potential of tumorigenesis were further investigated. RESULTS: The downregulation of OVOS2 significantly suppressed the proliferation of A375 cells and led to a G2/M phase block. The transwell cell migration assay showed that the reduced expression of OVOS2 also significantly inhibited the transmigration of A375 cells. The western blot results showed downregulated expression of p-FAK, p-AKT, and p-ERK. This was accompanied by the upregulated epithelial phenotypes E-cadherin and ß-catenin, and downregulated expression of mesenchymal phenotype N-cadherin after OVOS2 knockdown. The transplantation tumor experiment in BALB/C nude mouse showed that after an observation period of 32 days, the growth speed and weight of the transplanted tumors were significantly suppressed in the BALB/c nude mice subcutaneously injected with OVOS2 knocked-down A375 cells. CONCLUSION: The inhibition of OVOS2 had significant suppressive effects on the proliferation, motility, and migration capabilities of A375 cells, suggesting a crucial promotive role of OVOS2 in the pathogenesis and progression of CMM. The involved mechanisms are at least partly associated with the overactivation of FAK/MAPK/ERK and FAK/PI3K/AKT signals.

Expression analysis of ovostatin 2 reveals its involvement in proliferation, invasion and angiogenesis of cutaneous malignant melanoma.

The relationship of ovostatin 2 (OVOS2) expression with the clinicopathological features of cutaneous malignant melanoma (CMM) was investigated to identify OVOS2 expression in cutaneous melanocytic lesions, and to reveal whether OVOS2 has a function in melanoma progression. Eight specimens of CMM and paracancerous tissue were analyzed using real-time polymerase chain reaction (PCR) and western blot for the mRNA and protein expression of OVOS2, respectively. Immunohistochemical staining was performed on 52 CMM and 62 nevi, followed by clinicopathological significance analysis. The proliferative cells were visualized by staining with Ki-67 antibody. The intensity of angiogenesis was assessed by staining with vascular endothelial growth factor (VEGF). Real-time PCR and western blot analyses showed that OVOS2 was significantly upregulated in cutaneous melanoma than in paired normal skins. Immunohistochemistry showed that 86.5% (45/52) of malignant cases showed OVOS2 cytoplasmic expression compared with 29% (18/62) in benign nevi. OVOS2 expression was significantly higher in invasive and metastatic melanoma than in in situ melanoma (P < 0.01). Furthermore, OVOS2 expression was positively correlated with the known prognostic variables of melanoma including clinical stage, Clark level and Breslow depth. It was also significantly associated with ulcer status, Ki-67 labeling index and VEGF expression in primary melanoma. OVOS2 expression was significantly increased in CMM, which increased incrementally from benign nevi to melanoma and appeared to be involved in the progression of melanoma.