Table 2 Summary of published cohorts of LCH patients bearing BRAF V600E mutations in tissue
References | Race | BRAF V600E, (n%) | BRAF V600E in patients < 18 years, (n%) | Median age, range (year) | Gender ratio (M:F, ratio) | Sample type(s)—Method(s) | Features assessed with BRAF V600E | Feature(s) with significance |
|---|---|---|---|---|---|---|---|---|
Present cohort | Chinese | 45/84 (54%) | 45/84 (54%) | 2 years, 0–16 years | 88:60, 1.47 | FFPE tissue—NGS, 44/84 (52%); NGS and ddPCR, 45/84 (54%) Circulating DNA—NGS, 11/78 (14%); NGS and ddPCR, 18/78 (23%) | Onset age, gender, stage, involved organ, sample type, masses close to the lesion, TP53 mutation, recurrence | Sample type |
Tong [21] | Chinese | 0/18 (0%) | 0 | 28.5 years, 18–78 years | 14:4, 3.50 | FFPE tissue—Direct sequencing | NA | NA |
Zeng [22] | Chinese | 36/97 (37%) | 26/65 (40%) | 10 years, 1–63 years | 63:34, 1.85 | FFPE or PE tissue—Sanger sequencing, 31/97 (32%) FFPE or PE tissue—IHC, 36/97 (37%) | Disease-free survival, PDL1, FOXP3 + Tregs, GATA3 + /T-bet + ratio | Disease-free survival, PDL1, FOXP3 + Tregs |
Zeng [13] | Chinese | Same as group (22) | Â | Â | Â | Â | Age, gender, anatomic sites, stage, survival, recurrence | Age, recurrence |
Liu [43] | Chinese | 27/36 (75%) | 19/23 (83%) | 6 years, 1–56 years | 23:13, 1.77 | PE tissue—Sanger sequencing, 26/36 (72.2%) PE tissue—IHC, 25/31 (80.6%) | Age, sex, anatomic sites, stage, outcome | None |
Sasaki [44] | Japanese | 4/19 (21%) | 4/16 (25%) | 2 years, 0–71 years | 9:10, 0.90 | FFPE tissue—IHC and direct sequencing | NA | NA |
Hayase [45] | Japanese | 27/59 (46%) | 24/50 (49%) | 2.9 years, 0.3–17 years (children) 40.8 years, 19–67.1 years (adults) | 34:25, 1.36 | Fresh frozen and FFPE tissue—AS-qPCR and NGS | Sex, age at diagnosis, disease extent, response to first-line therapy, relapse, or CNS-related sequelae | MAP2K1 exon 2 in-frame deletion was related to the risk organ involvement |
Kobayashi [23] | Japanese | 9/23 (39%) | NA | 42 years, 1–79 years | 23:30, 0.77 | Frozen or FFPE tissue—IHC Cell-free DNA—AS-qPCR and ddPCR, 6/33 (18%) | NA | NA |
Go [46] | Korean | 6/27 (22%) | NA | NA, 0–50 years | NA | FFPE tissue—Sanger sequencing and AS-qPCR | Age, gender, anatomic sites, stage, outcome, clinicopathological features | None |
| Â | East Asian population | 154/363 (42%) | 118/238 (50%) | Â | 254:176, 1.44 | Â | Â | Â |
Alayed [47] | American | 8/50 (16%) | NA | 36.5 years, 1–78 years | 28:22, 1.27 | FFPE tissue—Pyrosequencing | Age, gender, anatomic sites, stage, overall survival | Age |
Badalian-Very [16] | American | 35/61 (57%) | 22/31 (71%) | 12 years, 0.9–61 years | 39:22, 1.77 | FFPE tissue—Pyrosequencing and/or OncoMap mass spectrometric genotyping | Age, gender, anatomic sites, stage | Age |
Ballester [32] | American | 15/26 (58%) | 15/26 (58%) | NA, 0.6–17 years | 14:12, 1.17 | FFPE tissue—AS-qPCR | NA | NA |
Berres [12] | American | 64/100 (64%) | 64/100 (64%) | NA, 2–8 years | 60:40, 1.50 | FFPE tissue—AS-qPCR and/or langerin + cell—Sanger sequencing Circulating DNA—AS-qPCR, 17/77 (22%) | Age, gender, stage, CNS risk lesions, Diabetes insipidus | None |
Brown [48] | American | 18/40 (45%) | 11/27 (41%) | 11.5 years, 0–84 years | 21:19, 1.11 | FFPE tissue—AS-PCR and NGS | Age, gender, anatomic sites | None |
Pina-Oviedo [49] | American | 0/7 (0%) | 0 | 54 years, 28–84 years | 4:3, 1.33 | FFPE tissue—Pyrosequencing, IHC and NGS | NA | NA |
Roden [50] | American | 19/54 (35%) | NA | 27.6 ± 21.8 years (mean ± SD) | 37:17, 2.18 | FFPE tissue—IHC and validated by AS-PCR and Sanger sequencing | Cumulative tobacco exposure | Cumulative tobacco exposure in PLCH |
| Â | American population | 159/338 (47%) | 112/184 (61%) | Â | 203:135, 1.50 | Â | Â | Â |
Haroche [51] | French | 11/29 (38%) | NA | NA, NA | NA | FFPE tissue—Pyrosequencing and IHC | NA | NA |
Heritier [19] | French | 173/315 (55%) | 173/315 (55%) | 3.2 years, 0–17.9 years | 167:148, 1.13 | FFPE tissue—Pyrosequencing or AS-qPCR or ddPCR or IHC | Age, gender, stage, involvement, follow-up years, 5-year relapse, death, permanent consequence, therapy | Median follow-up years, skin, risk organ, second-line therapy and/or rescue therapy requirement |
Satoh [24] | French | 9/16 (56%) | 8/15 (53%) | 7.595 years, 0–19 years | 8:8, 1.00 | Tissue—Pyrosequencing Whole blood—Pyrosequencing, 0/23 (0%) | Age of diagnosis, stage | None |
Bubolz [18] | German | 22/42 (52%) | NA | NA, (0.6–65 years) | 22:20, 1.10 | FFPE tissue—Pyrosequencing or BRAF 600/601 StripAssay and validated by Sanger sequencing | Age, gender, stage, anatomic sites, overall survival | CD1a |
Sahm [52] | German and Austrian | 34/89 (38%) | 16/47 (34%) | 22.5 years, 1–80 years | NA | FFPE tissue—IHC and direct sequencing | Age, proliferation rate (Ki-67), the activation of RAS pathway, strong expression of p53 | None |
Mehes [53] | Hungarian | 8/15 (53%) | 8/15 (53%) | 4 years, 0–18 years | 7:8, 0.875 | FFPE tissue—AS-qPCR/direct sequencing and IHC | Original sites, time point, clinical and histologic features, overall survival | Overall survival |
| Â | European population | 257/506 (51%) | 205/392 (52%) | Â | 204:184, 1.11 | Â | Â | Â |
Overall | Â | 570/1207 (47%) | 435/814 (53%) | Â | 661:495, 1.34 | Â | Â | Â |