West Cancer Center, U Tennessee, Memphis, TN
Matthew K Stein , Joanne Xiu , Michael Gary Martin , Axel Grothey , Philippe Prouet , Jeffrey Owsley , Forrest W Williard , Evan Scott Glazer , Paxton Vandiver Dickson , David Shibata , Danny Yakoub , Richard M. Goldberg , W. Michael Korn , Anthony Frank Shields , Jimmy J. Hwang , Heinz-Josef Lenz , Jeremiah Lee Deneve
Background: PM from GC or GEJ portend a poor prognosis and molecular differences are ill defined. Methods: We compared genomic profiles of primary (P) GC and GEJ with PM patients (pts) and other metastases (OM) sent to Caris Life Sciences. Testing comprised immunohistochemistry (IHC) including programmed death ligand 1 (PD-L1) combined positive score (CPS), copy number alterations (CNA), 592-gene next-generation sequencing (NGS), microsatellite instability (MSI) and tumor mutational burden (TMB). Results: 1366 cases were identified: 1041 GC (707 P, 98 PM, 236 OM) and 325 GEJ (248 P, 5 PM, 72 OM). PM were increased in GC versus GEJ (9% v. 2%, p < 0.0001). 91% GC and 93% GEJ were adenocarcinoma (AD); GC were more likely signet ring (SR) histology versus GEJ (11% v. 3%, p < 0.0001) and GC PM were more likely SR versus other OM or P (13% v. 12% v. 7%, p = 0.067). The mean age of PM pts (57 years) was younger than primary GC (63, p = 0.002) and OM (61; p = 0.044). More PM GC pts were female than P or OM (48% v. 35% v. 34%, p = 0.03). No molecular profiling differences were seen between GEJ and GC pts and they were combined for analysis; findings from 1246 AD pts are shown below (see Table). OM (9%, p = 0.041) had more CNA in CCNE1 than PM (2%, p = 0.041) or P (5%, p = 0.002). Conclusions: Compared to P and OM GC, PM pts were younger, more likely female and had a higher incidence of SR histology. PD-L1, HER2 IHC and ERBB2 CNA were reduced in PM versus P, suggesting novel therapeutic targets are needed.
Characteristic | PM (N = 87) | P (N = 893) | p-value (PM v. P) | OM (N = 266) | p-value (OM v. P) |
---|---|---|---|---|---|
TMB ≥10 mutations/Mb (%) | 18/87 (21) | 220/885 (25) | 0.388 | 65/261 (25) | 0.988 |
PD-L1 CPS 1+ (%) | 26/83 (31) | 412/855 (48) | 0.003 | 98/256 (38) | 0.005 |
PD-L1 CPS ≥10 (%) | 10/83 (12) | 120/855 (14) | 0.617 | 35/256 (14) | 0.883 |
MSI-high (%) | 3/86 (3) | 72/889 (8) | 0.125 | 10/266 (4) | 0.016 |
No. genes mutated ≥1% (%) | 46/592 (8) | 43/592 (7) | 0.635 | 42/592 (7) | 0.874 |
CDH1-mutated (%) | 11/86 (13) | 53/883 (6) | 0.016 | 18/265 (7) | 0.640 |
MUTYH-mutated (%) | 3/87 (3) | 4/891 (0) | 0.002 | 5/266 (2) | 0.020 |
ERBB2-mutated (%) | 2/87 (2) | 28/893 (3) | 0.665 | 2/266 (1) | 0.032 |
HER2-positive IHC (%) | 2/81 (2) | 70/796 (9) | 0.048 | 15/236 (6) | 0.232 |
ERBB2 CNA (%) | 1/85 (1) | 69/837 (8) | 0.019 | 19/255 (7) | 0.684 |
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