PTEN Protein Loss and Loss-of-Function Mutations in Gastric Cancers: The Relationship with Microsatellite Instability, EBV, HER2, and PD-L1 Expression
Abstract
:1. Introduction
2. Results
2.1. Clinicopathological Characteristics of Patients with PTEN-Mutated GC
2.2. Clinicopathologic Characteristics of PTEN Wild-Type GC
2.3. PTEN Mutations in Relationship with PTEN Protein Loss, MSI, EBV, and PD-L1 Expression
2.4. Co-Occurring Genetic Alterations Associated with PTEN Mutation
3. Discussion
4. Materials and Methods
4.1. Patients and Data Collection
4.2. Cancer Panel Test with NGS
4.3. Immunohistochemistry
4.4. MSI Test
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Case | Age | Sex | Specimen | Histology | HER2 | EBV | MSI | PD-L1 CPS (≥1) |
---|---|---|---|---|---|---|---|---|
1 | 70 | M | Stomach, biopsy | TADC, WD | - | - | MSS | - |
2 | 58 | M | Stomach, biopsy | TADC, MD | - | - | MSI | - |
3 | 47 | F | Stomach, biopsy | TADC, PD | - | - | MSS | + |
4 | 65 | M | Stomach, resection | TADC, PD | - | + | MSS | + |
5 | 50 | F | Stomach, resection | TADC, MD | - | - | MSS | - |
6 | 53 | F | Stomach, biopsy | TADC, PD | - | - | MSS | + |
7 | 69 | M | Stomach, biopsy | TADC, MD | - | - | MSS | - |
8 | 61 | M | Stomach, resection | TADC, PD | - | - | MSS | - |
9 | 85 | M | Stomach, biopsy | TADC, PD | - | - | MSS | + |
10 | 69 | M | Stomach, resection | TADC, MD | + | - | MSS | + |
11 | 66 | F | Stomach, resection | TADC, MD | + | - | MSS | - |
12 | 41 | M | Stomach, resection | TADC, PD | - | - | MSS | - |
13 | 64 | F | Stomach, resection | TADC, PD | - | - | MSS | - |
14 | 64 | M | Stomach, biopsy | TADC, PD | - | - | MSS | + |
15 | 47 | M | Stomach, biopsy | TADC, PD | - | NA | NA | NA |
16 | 51 | M | Stomach, biopsy | TADC, PD | - | - | MSS | - |
17 | 56 | F | Stomach, biopsy | TADC, PD | - | - | MSS | + |
18 | 79 | F | Stomach, resection | TADC, MD | - | - | MSI | + |
19 | 77 | M | Stomach, biopsy | TADC, PD | - | - | MSS | + |
20 | 59 | M | Stomach, biopsy | TADC, MD | - | - | MSS | + |
21 | 66 | F | Stomach, biopsy | TADC, PD | - | - | MSS | + |
22 | 40 | F | Stomach, biopsy | SRC | - | - | MSS | + |
23 | 61 | F | Stomach, resection | PADC, MD | + | - | MSI | + |
24 | 78 | M | Stomach, resection | TADC, PD | - | - | MSI | + |
25 | 53 | M | Stomach, resection | TADC, MD | + | - | MSS | + |
26 | 76 | F | Stomach, resection | TADC, MD | - | - | MSI | + |
27 | 54 | M | Stomach, resection | PADC, MD | - | - | MSS | + |
28 | 79 | M | Stomach, resection | TADC, MD | - | - | MSI | + |
29 | 70 | M | Stomach, resection | TADC, MD | - | - | MSS | + |
30 | 60 | M | Stomach, resection | TADC, PD | - | + | MSS | + |
31 | 56 | F | Stomach, resection | TADC, MD | - | - | MSI | + |
32 | 76 | M | Stomach, resection | TADC, MD | + | - | MSS | + |
33 | 74 | M | Stomach, resection | TADC, MD | - | - | MSS | + |
34 | 76 | M | Stomach, resection | TADC, MD | - | - | MSI | + |
PTEN-Mutated (n = 34) | PTEN WT (n = 288) | p-Value | |
---|---|---|---|
Sex | 0.9805 | ||
Male | 22 (64.7%) | 181 (62.8%) | |
Female | 12 (35.3%) | 107 (37.2%) | |
Age (median, range) | 64 (40–85) | 61 (29–85) | 0.175 |
PTEN IHC | 5.232 × 10−10 | ||
Intact | 15 (44.1%) | 253 (87.8%) | |
loss | 19 (55.9%) | 35 (12.2%) | |
MSI status | 3.936 × 10−8 | ||
MSI | 8 (23.5%) | 9 (3.1%) | |
MSS | 25 (73.5%) | 279 (96.9%) | |
NA | 1 (3.0%) | 0 (0%) | |
EBV | 0.0071 | ||
positive | 2 (5.9%) | 7 (2.4%) | |
negative | 31 (91.2%) | 281 (97.6%) | |
NA | 1 (2.9%) | 0 (0%) | |
HER2 | 0.7945 | ||
positive | 5 (14.7%) | 39 (13.5%) | |
negative | 29 (85.3%) | 249 (86.5%) | |
PD-L1 CPS | 0.111 | ||
≥1 | 24 (70.6%) | 182 (63.2%) | |
0 | 9 (26.5%) | 105 (36.5%) | |
NA | 1 (2.9%) | 1 (0.3%) |
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Kim, B.; Kang, S.Y.; Kim, D.; Heo, Y.J.; Kim, K.-M. PTEN Protein Loss and Loss-of-Function Mutations in Gastric Cancers: The Relationship with Microsatellite Instability, EBV, HER2, and PD-L1 Expression. Cancers 2020, 12, 1724. https://doi.org/10.3390/cancers12071724
Kim B, Kang SY, Kim D, Heo YJ, Kim K-M. PTEN Protein Loss and Loss-of-Function Mutations in Gastric Cancers: The Relationship with Microsatellite Instability, EBV, HER2, and PD-L1 Expression. Cancers. 2020; 12(7):1724. https://doi.org/10.3390/cancers12071724
Chicago/Turabian StyleKim, Binnari, So Young Kang, Deokgeun Kim, You Jeong Heo, and Kyoung-Mee Kim. 2020. "PTEN Protein Loss and Loss-of-Function Mutations in Gastric Cancers: The Relationship with Microsatellite Instability, EBV, HER2, and PD-L1 Expression" Cancers 12, no. 7: 1724. https://doi.org/10.3390/cancers12071724