Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Case Selection
2.2. Immunohistochemistry (IHC)
2.3. HER2 Chromogenic In Situ Hybridization (CISH)
2.4. EBER In Situ Hybridization (ISH)
2.5. IHC Profiling for Molecular Classification
2.6. Construction of Virtual Biopsies
2.7. Statistical Analysis
3. Results
3.1. Clinical Characteristics
3.2. Histopathological Characteristics
3.3. CLDN18 Expression, Prevalence and Clinicopathological Associations
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patients’ Characteristics | Total 350 n. (%) | CLDN18 < 75% Tot 233 n. (% of the Total) | CLDN18 ≥ 75% Tot 117 n. (% of the Total) | p Value | |
---|---|---|---|---|---|
Sex | Male | 218 (62.3) | 138 (39.4) | 80 (22.9) | 0.1214 |
Female | 132 (37.7) | 95 (27.1) | 37 (10.6) | ||
Age | <70 | 209 (59.7) | 126 (36.0) | 83 (23.7) | 0.0035 |
>70 | 141 (40.3) | 107 (30.6) | 34 (9.7) | ||
ECOG PS | 0 | 176 (51.2) | 111 (32.3) | 65 (18.9) | 0.1571 |
≥1 | 168 (48.8) | 119 (34.6) | 49 (14.2) | ||
Primary resection | Yes | 185 (52.9) | 126 (36.0) | 59 (16.9) | 0.5949 |
No | 165 (47.1) | 107 (30.6) | 58 (16.6) | ||
pT | 1–2 | 18 (5.1) | 14 (4.0) | 4 (1.1) | 0.4325 |
3–4 | 136 (38.9) | 93 (26.6) | 43 (12.3) | ||
Missing | 196 (6) | 126 (36.0) | 70 (20.0) | ||
pN | 0–1 | 54 (15.4) | 44 (12.6) | 10 (2.9) | 0.0407 |
2–3 | 98 (28.0) | 62 (17.7) | 36 (10.3) | ||
Missing | 198 (56.57) | 127 (36.3) | 71 (20.3) | ||
Stage at first tumor diagnosis | I–II | 37 (10.6) | 33 (9.4) | 4 (1.1) | 0.0033 |
III–IV | 299 (85.4) | 192 (54.9) | 107 (30.6) | ||
Missing | 14 (4.0) | 8 (2.3) | 6 (1.7) | ||
Metastatic disease | Synchronous | 253 (72.3) | 163 (46.6) | 90 (25.7) | 0.2124 |
Metachronous | 97 (27.7) | 70 (20.0) | 27 (7.7) | ||
Sites of metastases at baseline | liver yes | 132 (37.7) | 99 (28.3) | 33 (9.4) | 0.0130 |
liver no | 218 (62.3) | 134 (38.3) | 84 (2) | ||
nodes yes | 141 (40.3) | 95 (27.1) | 46 (13.1) | 0.8835 | |
nodes no | 209 (59.7) | 138 (39.4) | 71 (20.3) | ||
lung yes | 35 (10.0) | 26 (7.4) | 9 (2.6) | 0.4060 | |
lung no | 315 (90.0) | 207 (59.1) | 108 (30.9) | ||
peritoneum yes | 146 (41.7) | 79 (22.6) | 67 (19.1) | <0.001 | |
peritoneum no | 204 (58.3) | 154 (44.0) | 50 (14.3) | ||
bone yes | 30 (8.6) | 17 (4.9) | 13 (3.7) | 0.3172 | |
bone no | 320 (91.4) | 216 (61.7) | 104 (29.7) | ||
brain yes | 5 (1.4) | 4 (1.1) | 1 (0.3) | 0.8700 | |
brain no | 345 (98.6) | 229 (65.4) | 116 (33.1) | ||
other yes | 33 (9.4) | 22 (6.3) | 11 (3.1) | 1.000 | |
other no | 317 (90.6) | 211 (60.3) | 106 (30.3) | ||
Location | G | 280 (80.0) | 190 (54.3) | 90 (25.7) | 0.3799 |
GEJ | 70 (20.0) | 43 (12.3) | 27 (7.7) | ||
Histology | Mixed YES | 39 (11.1) | 25 (7.1) | 14 (4.0) | 0.8676 |
Mixed NO | 311 (88.9) | 208 (59.4) | 103 (29.4) | ||
PCC YES | 65 (18.6) | 42 (1) | 23 (6.6) | 0.8222 | |
PCC NO | 285 (81.4) | 191 (54.6) | 94 (26.9) | ||
PCC–signet ring YES | 52 (14.9) | 28 (8.0) | 24 (6.9) | 0.051 | |
PCC–signet ring NO | 298 (85.1) | 205 (58.6) | 93 (26.6) | ||
Rare YES | 14 (4.0) | 9 (2.6) | 5 (1.4) | 1.000 | |
Rare NO | 336 (96.0) | 224 (6) | 112 (3) | ||
Tubular YES | 180 (51.4) | 129 (36.9) | 51 (14.6) | 0.0500 | |
Tubular NO | 170 (48.6) | 104 (29.7) | 66 (18.9) | ||
Grading | G1 | 13 (3.7) | 8 (2.3) | 5 (1.4) | 0.0834 |
G2-G3 | 167 (47.7) | 121 (34.6) | 46 (13.1) | ||
NE | 170 (48.6) | 104 (29.7) | 66 (18.9) | ||
Lauren | Diffuse YES | 117 (33.4) | 70 (20.0) | 47 (13.4) | 0.0760 |
No | 233 (66.6) | 163 (46.6) | 70 (20.0) | ||
Intestinal YES | 186 (53.1) | 132 (37.7) | 54 (15.4) | 0.0813 | |
NO | 164 (46.9) | 101 (28.9) | 63 (18.0) | ||
Mixed YES | 39 (11.1) | 25 (7.1) | 14 (4.0) | 0.8676 | |
NO | 311 (88.9) | 208 (59.4) | 103 (29.4) |
Patients’ Characteristics | Total 350 n. (%) | CLDN18 < 75% Tot 233 n. (% of the Total) | CLDN18 ≥ 75% Tot 117 n. (%of the Total) | p Value | |
---|---|---|---|---|---|
MMRd | Yes | 54 (15.4) | 39 (11.1) | 15 (4.3) | 0.2424 |
No | 296 (84.6) | 194 (55.4) | 102 (29.1) | ||
HER 2 status | Positive | 52 (14.9) | 35 (10.0) | 17 (4.9) | 1.000 |
Negative | 298 (85.1) | 198 (56.6) | 100 (28.6) | ||
PD-L1 CPS ≥ 1 | Yes | 98 (28) | 68 (19.4) | 30 (8.6) | 0.5685 |
No | 252 (72) | 165 (47.14) | 87 (24.86) | ||
PD-L1 CPS ≥ 5 | Yes | 71 (20.29) | 50 (14.29) | 21 (6) | 0.5290 |
No | 279 (79.71) | 183 (52.29) | 96 (27.43) | ||
EBER | Positive | 8 (2.3) | 1 (0.3) | 7 (20.0) | 0.0024 |
Negative | 342 (97.7) | 232 (66.3) | 110 (31.4) | ||
p53 status | Altered | 168 (48.0) | 111 (31.7) | 57 (16.3) | 0.9676 |
wild type | 181 (52.0) | 121 (34.6) | 60 (17.1) | ||
E-Cadheri n status | Positive | 268 (77.0) | 177 (50.9) | 91 (26.1) | 0.9148 |
Negative | 80 (23.0) | 54 (15.5) | 26 (7.5) |
Patients’ Characteristics | Total 350 n. (%) | CLDN18 < 75% Tot 233 n. (%) | CLDN18 ≥ 75% Tot 117 n. (%) | p Value | |
---|---|---|---|---|---|
TCGA | CIN NO | 128 (36.8) | 85 (24.4) | 43 (12.4) | 1.000 |
YES | 220 (63.2) | 146 (42.0) | 74 (21.3) | ||
EBV NO | 339 (97.4) | 229 (65.8) | 110 (31.6) | 0.0080 | |
YES | 9 (2.6) | 2 (0.6) | 7 (2.0) | ||
GS NO | 283 (81.3) | 187 (53.7) | 96 (27.6) | 0.9180 | |
YES | 65 (18.7) | 44 (12.6) | 21 (6.0) | ||
MSI NO | 294 (84.5) | 192 (55.2) | 102 (29.3) | 0.4053 | |
YES | 54 (15.5) | 39 (11.2) | 15 (4.3) | ||
ACRG | MSI NO | 294 (84.5) | 192 (55.2) | 102 (29.3) | 0.4053 |
YES | 54 (15.5) | 39 (11.2) | 15 (4.3) | ||
MSS/EMT NO | 280 (80.5) | 187 (53.7) | 93 (26.7) | 0.8551 | |
YES | 68 (19.5) | 44 (12.6) | 24 (6.9) | ||
MSS/P53+ NO | 227 (65.2) | 145 (41.7) | 82 (23.6) | 0.2170 | |
YES | 121 (34.8) | 86 (24.7) | 35 (10.1) | ||
MSS/P53- NO | 243 (69.8) | 169 (48.6) | 74 (21.3) | 0.0752 | |
YES | 105 (30.2) | 62 (17.8) | 43 (12.4) | ||
Birkman | EBV NO | 340 (97.4) | 230 (65.9) | 110 (31.5) | 0.0078 |
YES | 9 (2.6) | 2 (0.6) | 7 (2.0) | ||
EBV NEG, MSS, P53 WT YES | 215 (61.6) | 145 (41.6) | 70 (2.0) | 0.7131 | |
NO | 134 (38.4) | 87 (24.9) | 47 (13.5) | ||
MSI NO | 295 (84.5) | 193 (55.3) | 102 (29.2) | 0.4144 | |
YES | 54 (15.5) | 39 (11.2) | 15 (4.3) | ||
P53 ABERRANT NO | 197 (56.5) | 128 (36.7) | 69 (19.8) | 0.5742 | |
YES | 152 (43.6) | 104 (29.8) | 48 (13.8) | ||
Ahn | C1 NO | 339 (97.4) | 229 (65.8) | 110 (31.6) | 0.0080 |
YES | 9 (2.6) | 2 (0.6) | 7 (2.0) | ||
C2 NO | 294 (84.5) | 192 (55.2) | 102 (29.3) | 0.4053 | |
YES | 54 (15.5) | 39 (11.2) | 15 (4.3) | ||
C3 NO | 283 (81.3) | 187 (53.7) | 96 (27.6) | 0.9180 | |
YES | 65 (18.7) | 44 (12.6) | 21 (6.0) | ||
C4 NO | 230 (66.1) | 146 (42.0) | 84 (24.1) | 0.1390 | |
YES | 118 (33.9) | 85 (24.4) | 33 (9.5) | ||
C5 NO | 246 (70.7) | 170 (48.9) | 76 (21.8) | 0.1218 | |
YES | 102 (29.3) | 61 (17.5) | 41 (11.8) |
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Pellino, A.; Brignola, S.; Riello, E.; Niero, M.; Murgioni, S.; Guido, M.; Nappo, F.; Businello, G.; Sbaraglia, M.; Bergamo, F.; et al. Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas. J. Pers. Med. 2021, 11, 1095. https://doi.org/10.3390/jpm11111095
Pellino A, Brignola S, Riello E, Niero M, Murgioni S, Guido M, Nappo F, Businello G, Sbaraglia M, Bergamo F, et al. Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas. Journal of Personalized Medicine. 2021; 11(11):1095. https://doi.org/10.3390/jpm11111095
Chicago/Turabian StylePellino, Antonio, Stefano Brignola, Erika Riello, Monia Niero, Sabina Murgioni, Maria Guido, Floriana Nappo, Gianluca Businello, Marta Sbaraglia, Francesca Bergamo, and et al. 2021. "Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas" Journal of Personalized Medicine 11, no. 11: 1095. https://doi.org/10.3390/jpm11111095
APA StylePellino, A., Brignola, S., Riello, E., Niero, M., Murgioni, S., Guido, M., Nappo, F., Businello, G., Sbaraglia, M., Bergamo, F., Spolverato, G., Pucciarelli, S., Merigliano, S., Pilati, P., Cavallin, F., Realdon, S., Farinati, F., Dei Tos, A. P., Zagonel, V., ... Fassan, M. (2021). Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas. Journal of Personalized Medicine, 11(11), 1095. https://doi.org/10.3390/jpm11111095