Potential prognostic value of PD-L1 and NKG2A expression in Indonesian patients with skin nodular melanoma.

OBJECTIVE: Biomarker mRNA levels have been suggested to be predictors of patient survival and therapy response in melanoma cases. This study aimed to investigate the correlations between the mRNA expression levels of PD-L1 and NKG2A in melanoma tissue with clinicopathologic characteristics and survival in Indonesian primary nodular melanoma patients. RESULTS: Thirty-one tissue samples were obtained; two were excluded from survival analysis due to Breslow depth of less than 4 mm. The median survival of upregulated and normoregulated PD-L1-patients were 15.800 ± 2.345 and 28.945 ± 4.126 months, respectively. However, this difference was not significant statistically (p = 0.086). Upregulated and normoregulated NKG2A patients differed very little in median survival time (25.943 ± 7.415 vs 26.470 ± 3.854 months; p = 0.981). Expression of PD-L1 and NKG2A were strongly correlated (rs: 0.787, p < 0.001). No clinicopathologic associations with PD-L1 and NKG2A mRNA levels were observed. These results suggest that PD-L1 may have potential as a prognostic factor. Although an unlikely prognostic factor, NKG2A may become an adjunct target for therapy. The strong correlation between PD-L1 and NKG2A suggests that anti-PD-1 and anti-NKG2A agents could be effective in patients with PD-L1 upregulation. The mRNA levels of these two genes may help direct choice of immunotherapy and predict patient outcomes.

BRAF V600 mutation profiling in primary skin nodular melanoma in Indonesia: an analysis using high resolution pyrosequencing.

OBJECTIVE: We aimed to investigate the prevalence and type of BRAF V600 mutations and the associations with clinicopathological variables in primary skin nodular melanoma cases in Yogyakarta and Central Java, Indonesia using pyrosequencing. RESULTS: BRAF V600 mutations of the V600E type were found in 21 (53.85%) specimens. The variant allele frequencies (VAFs) ranged from 5.07 to 94.70%, averaging 29.05%. However, most cases had low VAFs, with 13 (61.9%) specimens below 20% and 4 (19.05%) below 10%.

Low BRAF V600 mutation prevalence in primary skin nodular melanoma in Indonesia: a real-time PCR detection among Javanese patients.

BACKGROUND: Cutaneous melanoma is a rare, aggressive skin malignancy with a high mortality rate. Although only contributing 7.6% of the cases worldwide, Asia is responsible for 18.6% of deaths from cutaneous melanoma. BRAF V600 mutation presents a potential prognostic predictor in melanoma. Unfortunately, studies on that mutation in melanoma, particularly nodular subtype, in Indonesia are still scarce. This research aimed to investigate the prevalence of BRAF V600 mutation in primary skin nodular melanoma in Yogyakarta and Central Java, Indonesia. Its association with clinicopathological parameters was also analyzed. METHODS: Forty paraffin-embedded tissue samples from primary skin nodular melanoma cases in 2011-2018 were collected from the two biggest referral hospitals in Yogyakarta and Central Java, Indonesia. The BRAF V600 mutation status was assessed using qualitative real-time PCR and its associations with age, sex, anatomic location, lymph node metastasis, tumor thickness, ulceration, mitotic index, necrosis, lymphovascular invasion, and tumor-infiltrating lymphocytes were analyzed. RESULTS: BRAF V600 mutations were found in 4 (10%) samples. These mutations were significantly associated with the central (non-extremity) region (p = 0.013) and presence of lymphovascular invasion (p = 0.005). However, it was not associated with any other variables analyzed in this study. CONCLUSION: The prevalence of BRAF V600 mutation in Indonesian primary skin nodular melanoma cases is low and significantly associated with anatomic location and lymphovascular invasion. It is lower than prevalences in other Asian populations as well as in Caucasian populations and suggests that melanoma cases in Javanese people may have distinct clinicopathological characteristics from other Asian ethnicities.