Table 2.
Integration of NGS Data for Discriminating MPLCs from Intrapulmonary Metastasis
| Author [year] | MLC, n |
Reference standard |
Inconclusivea, n (%) |
Diagnostic methods | Genes panel | MPLCs, n | Inconclusiveb, n (%) | NGS: referc (same, n) | Common gene mutations | Convergent evolution |
| Patel et al [2017]52 | 11 | AJCC | 3 (27) | NGS | 50 | 8 | 0 (0)d | 8: 10 (8) | EGFR/KRAS/TP53/BRAF |
KRAS: G12V+G12A/C, TP53: Q192X+N210fs*37 |
| Saab et al [2017]53 | 18 | clinicopathologic, radiologic feature |
6 (35) | Histology + NGS | 50 | 17 | 1 (8) | N/A | KRAS/EGFR/TP53/BRAF/KIT/PI3KCA |
KRAS: G12V+G12D/ Q61H EGFR: 19del+L858R |
| Roepman et al [2018]54 | 50 | IHC+AJCC | 0 (0) | NGS | 50 | 32 | 2 (4) | 32: 32 (23) | KRAS/TP53/EGFR/BRAF/STK11/CDKN2A | TP53, EGFR, KRAS |
| Takahashi et al [2018]55 | 37 | MM, histopathology |
0 (0) 17 (46) |
NGS | 20 | 17 | 0 (0)a | 17: 34 (15) 17: 17 (9) |
EGFR/TP53/KRAS/STK11 |
EGFR: L858R+19del /S768I HER-2: F547del+K1152fs |
| Chang et al [2019]56 | 60 (76pairs) | CHA | 23 (30) (pairs) | NGS | 341 ~468 | 41 (51 pairs) | 1 (1) (pairs) | 51: 56 (45) (pairs) | EGFR/KRAS/ALK/ROS1/MET |
KRAS: G12C/D/V+G12C/D/A/Q61L EGFR: L858R+L858R/19del /S768I |
| Donfrancesco et al [2020]57 | 24 | Pathological featurese | N/A | NGS | 22 | 15 | 3 (13) | 15: 14 (9) (subtype) | KRAS/TP53/STK11/HER-2/EGFR/MET/BRAF |
KRAS: G12V+G12C/D KRAS: G12D+G12A/C |
| Higuchi et al [2020]58 | 37 | histopathology, AJCC | N/A | NGS | 53 | 29 | N/A | 29: 31 (27) 29: 33 (26) |
TP53/KRAS/EGFR/BRAF/CDKN2A/STK11 |
EGFR: L858R+exon 21ins KRAS: G12C+G12C |
Notes: a,bInconclusive numbers based on reference diagnostic criteria and NGS, respectively; cNumbers of MPLC patients diagnosed using NGS or other reference standards, the parentheses indicate numbers of patients diagnosed with MPLCs by both standards; dNone was inconclusive when both tumors sharing at least one mutation were regarded as metastatic; Pathological featurese defined as predominant subtypes, lepidic component, nucleoli size, and TTF-1 expression.
Abbreviations: NGS, next-generation sequencing; MPLCs, multiple primary lung cancers; MLC, multifocal lung cancers; IHC, immunohistochemistry; AJCC, American joint Committee on cancer; MM, Martini Melamed criterion; CHA, comprehensive histologic assessment.