A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability
Abstract
:1. Introduction
2. Results
2.1. A Molecular Subtype Classification for GC Based on CISH/IHC
2.2. NGS Analysis by Subtype
2.3. Differences between GC Subtypes and Patient Prognosis
2.4. Response to Chemotherapy in GC Subtypes
2.5. A Low-Cost Stratification System for GC Patients
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Hematoxylin and Eosin and Immunohistochemistry (IHC) Assays
4.3. IHC for HER2 and PDL1
4.4. Epstein–Barr Virus (EBV) and Mismatch Repair (MMR) Status Determination
4.5. E-Cadherin and p53 Status Determination
4.6. Genomic Analysis
4.7. Outcomes and Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Characteristic | Units (IQR or %) |
---|---|
Median OS; months | 30 (16–61) |
Males | 60 (66) |
Females | 31 (34) |
Median age; years | 63 (55–73) |
Stage | |
I/II | 33 (36) |
III | 46 (51) |
IV | 12 (13) |
Lauren histotype | |
Intestinal | 27 (37) |
Diffuse | 31 (42) |
Mixed | 15 (21) |
WHO classification | |
Adenocarcinoma | 77 (88) |
Undifferentiated carcinoma | 8 (9) |
Adeno-squamous carcinoma | 3 (3) |
Primary tumor location | |
Proximal | 26 (30) |
Medial | 30 (34) |
Distal | 27 (31) |
Multiple | 4 (5) |
Signet ring cells | |
None | 58 (64) |
<50% | 27 (30) |
≥50% | 6 (6) |
HER2+ status | 12 (13) |
PDL1+ status | 26 (29) |
EBV+ status | 12 (13) |
MMR-deficient | 13 (14) |
p53+ status | 39 (43) |
E-cadherin loss | 15 (17) |
Comorbidities | |
None | 46 (51) |
1 | 20 (22) |
2 | 18 (20) |
≥3 | 7 (8) |
Characteristic | MMR-D n = 11 | EBV+ n = 12 | p53+ n = 18 | p53– n = 35 | EMT-Like n = 15 | Total n = 91 | p-Value |
---|---|---|---|---|---|---|---|
Median OS; Months (range) | 64 (17–98) | 38 (20.5–57) | 28 (13–40) | 39.5 (18–62) | 16 (12–29) | 30 (16–61) | 0.01 |
Males; n (%) | 6 (55) | 11 (92) | 11 (61) | 22 (63) | 10 (67) | 60 (66) | 0.31 |
Median age; years (IQR 1) | 66 (64–70) | 57 (52–69) | 63.5 (56–71) | 64.5 (55–76) | 57 (50–75) | 63.5 (55–73) | 0.22 |
Stage; n (%) | |||||||
I/II | 7 (64) | 6 (50) | 9 (50) | 10 (29) | 1 (7) | 33 (36) | 0.058 |
III | 4 (36) | 4 (33) | 7 (39) | 20 (57) | 11 (73) | 46 (51) | |
IV | 0 | 2 (17) | 2 (11) | 5 (14) | 3 (20) | 12 (13) | |
Primary tumor; n (%) | |||||||
Proximal | 1 (9) | 9 (75) | 5 (29) | 8 (25) | 3 (20) | 26 (30) | 0.081 |
Medial | 3 (27) | 2 (17) | 5 (29) | 14 (44) | 6 (40) | 30 (34) | |
Distal | 7 (64) | 1 (8) | 6 (35) | 8 (25) | 5 (33) | 27 (31) | |
Multiple | 0 | 0 | 1 (6) | 2 (6) | 1 (7) | 4 (5) | |
IHC 2; n (%) | |||||||
HER2+ | 1 (9) | 0 | 6 (33) | 5 (14) | 0 | 12 (13) | 0.037 |
PDL1+ | 3 (27) | 11 (92) | 5 (28) | 5 (14) | 2 (13) | 26 (29) | <0.001 |
Signet ring cells; n (%) | |||||||
No | 7 (64) | 12 (100) | 14 (78) | 18 (51) | 7 (47) | 58 (64) | 0.017 |
<50% | 4 (36) | 0 | 3 (17) | 12 (34) | 8 (53) | 27 (30) | |
≥50% | 0 | 0 | 1 (6) | 5 (14) | 0 | 6 (7) | |
Lauren histotype; n (%) | |||||||
Diffuse | 5 (56) | 2 (29) | 3 (20) | 14 (50) | 7 (50) | 31 (42) | 0.038 |
Intestinal | 2 (22) | 4 (57) | 10 (67) | 10 (36) | 1 (7) | 29 (40) | |
Mixed | 2 (22) | 1 (14) | 2 (13) | 4 (14) | 6 (43) | 13 (18) |
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Pinto, M.P.; Córdova-Delgado, M.; Retamal, I.N.; Muñoz-Medel, M.; Bravo, M.L.; Durán, D.; Villanueva, F.; Sanchez, C.; Acevedo, F.; Mondaca, S.; et al. A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability. Cancers 2020, 12, 1863. https://doi.org/10.3390/cancers12071863
Pinto MP, Córdova-Delgado M, Retamal IN, Muñoz-Medel M, Bravo ML, Durán D, Villanueva F, Sanchez C, Acevedo F, Mondaca S, et al. A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability. Cancers. 2020; 12(7):1863. https://doi.org/10.3390/cancers12071863
Chicago/Turabian StylePinto, Mauricio P., Miguel Córdova-Delgado, Ignacio N. Retamal, Matías Muñoz-Medel, M. Loreto Bravo, Doris Durán, Francisco Villanueva, César Sanchez, Francisco Acevedo, Sebastián Mondaca, and et al. 2020. "A Molecular Stratification of Chilean Gastric Cancer Patients with Potential Clinical Applicability" Cancers 12, no. 7: 1863. https://doi.org/10.3390/cancers12071863