The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer
Abstract
:1. Introduction
2. Results
2.1. Expression Status of p53 in CRCs
2.2. p53 Immunoreactivity Correlated with PHH3 Expression
2.3. Survival Analyses of Patients with CRC According to p53 Immunoreactivity
2.4. Survival Analyses of Patients with CRC According to CDX2 and ALCAM Expression
3. Discussion
4. Materials and Methods
4.1. Tissue Samples
4.2. Immunohistochemistry
4.3. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Total No. | p53 Immunoreactivity | |||||||
---|---|---|---|---|---|---|---|---|
262 | (100%) | Wild-Type 59 (23%) | Overexpression 143 (55%) | Cytoplasmic Expression 10 (4%) | Complete Loss 50 (19%) | p-Value | ||
Sex | 0.49 | a | ||||||
Male | 139 | [53%] | 36 [61%] | 73 [51%] | 4 [40%] | 26 [52%] | ||
Female | 123 | [47%] | 23 [39%] | 70 [49%] | 6 [60%] | 24 [48%] | ||
Age, years (Mean ± S.D.) | 68.6 ± 12.6 | 68.5 ± 14.1 | 68.5 ± 12.0 | 70.8 ± 7.7 | 69.0 ± 12.9 | 0.79 | b | |
Size, cm (Mean ± S.D.) | 5.0 ± 2.6 | 5.9 ± 2.6 † | 4.9 ± 2.7 | 4.5 ± 1.9 | 4.3 ± 1.8 | 0.0056 | b | |
Tumor location | 0.10 | c | ||||||
Right-sided colon | 120 | [46%] | 35 [59%] | 58 [40%] | 2 [20%] | 25 [50%] | ||
Left-sided colon | 84 | [32%] | 16 [27%] | 51 [36%] | 5 [50%] | 12 [24%] | ||
Rectum | 58 | [22%] | 8 [14%] | 34 [24%] | 3 [30%] | 13 [26%] | ||
pT stage | 0.31 | a | ||||||
pT2 | 36 | [13%] | 8 [14%] | 18 [13%] | 1 [10%] | 9 [18%] | ||
pT3 | 182 | [70%] | 42 [71%] | 103 [72%] | 9 [90%] | 28 [56%] | ||
pT4 | 44 | [16%] | 9 [15%] | 22 [15%] | 0 [0%] | 13 [26%] | ||
Histological differentiation | 0.73 | a | ||||||
Well to moderately | 235 | [90%] | 51 [86%] | 129 [90%] | 10 [100%] | 45 [90%] | ||
Poorly | 27 | [10%] | 8 [14%] | 14 [10%] | 0 [0%] | 5 [10%] | ||
Mucus production | 0.0015 | a | ||||||
Positive | 14 | [5%] | 9 [15%] †† | 2 [1%] | 0 [0%] | 3 [6%] | ||
Negative | 248 | [95%] | 50 [85%] | 141 [99%] | 10 [100%] | 47 [94%] | ||
Lymph node metastasis | 0.19 | a | ||||||
Positive | 122 | [49%] | 21 [38%] | 67 [51%] | 5 [50%] | 29 [59%] | ||
Negative | 124 | [51%] | 34 [62%] | 65 [49%] | 5 [50%] | 20 [41%] | ||
Peritoneal metastasis | a | |||||||
Positive | 49 | [19%] | 7 [12%] | 32 [22%] | 0 [0%] | 10 [20%] | 0.15 | |
Negative | 213 | [81%] | 52 [88%] | 111 [78%] | 10 [100%] | 40 [80%] | ||
Distant organ metastasis | a | |||||||
Positive | 43 | [16%] | 5 [8%] | 28 [20%] | 0 [0%] | 10 [20%] | 0.11 | |
Negative | 219 | [84%] | 54 [92%] | 115 [80%] | 10 [100%] | 40 [80%] | ||
Operation status | 0.23 | a | ||||||
Complete resection | 230 | [88%] | 56 [95%] | 122 [85%] | 9 [90%] | 43 [86%] | ||
Incomplete resection | 32 | [12%] | 3 [5%] | 21 [15%] | 1 [10%] | 7 [14%] | ||
MMR system status | a | |||||||
Deficient | 30 | [12%] | 19 [32%] ††† | 8 [6%] | 1 [10%] | 2 [4%] | <0.0001 | |
Preserved | 232 | [88%] | 40 [68%] | 135 [94%] | 9 [90%] | 48 [96%] |
Total No. | p53 Immunoreactivity | ||||||
---|---|---|---|---|---|---|---|
262 | (100%) | Wild-Type 59 (23%) | Overexpression 143 (55%) | Cytoplasmic Expression 10 (4%) | Complete Loss 50 (19%) | p-Value | |
CDX2 | 0.0031 | ||||||
Positive | 233 | [89%] | 44 [75%] † | 132 [92%] | 10 [100%] | 47 [94%] | |
Decreased or lost | 29 | [11%] | 15 [25%] | 11 [8%] | 0 [0%] | 3 [6%] | |
ALCAM | 0.0016 | ||||||
Positive | 76 | [29%] | 26 [44%] | 28 [21%] †† | 3 [30%] | 19 [38%] | |
Negative | 186 | [71%] | 33 [56%] | 115 [79%] | 7 [70%] | 31 [62%] | |
Stem-like immunophenotype | 0.19 | ||||||
Positive | 10 | [4%] | 5 [8%] | 3 [2%] | 0 [0%] | 2 [4%] | |
Negative | 252 | [96%] | 54 [92%] | 140 [98%] | 10 [100%] | 48 [96%] |
Total No. | p53 Immunoreactivity | |||||
---|---|---|---|---|---|---|
262 (100%) | Wild-Type 59 (23%) | Overexpression 143 (55%) | Cytoplasmic Expression 10 (4%) | Complete Loss 50 (19%) | p-Value | |
PHH3 (/HPF) | 7.0 (3, 12) | 5.0 (2.0, 9.0) † | 7.0 (4.0, 13.0) | 6.5 (2.3, 14.0) | 6.0 (3.3, 11.0) | 0.046 |
CCNA (%) | 36.4 (28.3, 44.7) | 34.3 (26.8, 40.9) | 37.3 (28.0, 45.2) | 42.8 (35.7, 46.0) | 37.0 (29.6, 45.4) | 0.18 |
GMNN (%) | 37.1 (28.4, 43.7) | 34.4 (27.7, 43.4) | 37.2 (27.3, 44.3) | 40.9 (38.7, 54.9) | 38.2 (30.0, 43.6) | 0.21 |
Ki-67 (%) | 49.2 (34.2, 62.0) | 48.3 (34.9, 65.5) | 46.0 (31.6, 61.5) | 58.5 (47.6, 62.6) | 50.9 (36.5, 61.7) | 0.65 |
Hazard | 95% CI | |||
---|---|---|---|---|
Ratio | Min | Max | p-Value | |
Well to moderately differentiated histology | 0.17 | 0.09 | 0.33 | <0.0001 |
Age (<70) | 0.52 | 0.30 | 0.91 | 0.021 |
Sex (female) | 0.55 | 0.31 | 0.99 | 0.046 |
p53 complete loss | 2.16 | 1.21 | 3.86 | 0.0087 |
Incomplete resection | 2.65 | 1.31 | 5.35 | 0.0068 |
Peritoneal metastasis | 5.32 | 2.97 | 9.54 | <0.0001 |
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Nagao, K.; Koshino, A.; Sugimura-Nagata, A.; Nagano, A.; Komura, M.; Ueki, A.; Ebi, M.; Ogasawara, N.; Tsuzuki, T.; Kasai, K.; et al. The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer. Int. J. Mol. Sci. 2022, 23, 3252. https://doi.org/10.3390/ijms23063252
Nagao K, Koshino A, Sugimura-Nagata A, Nagano A, Komura M, Ueki A, Ebi M, Ogasawara N, Tsuzuki T, Kasai K, et al. The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer. International Journal of Molecular Sciences. 2022; 23(6):3252. https://doi.org/10.3390/ijms23063252
Chicago/Turabian StyleNagao, Kazuhiro, Akira Koshino, Akane Sugimura-Nagata, Aya Nagano, Masayuki Komura, Akane Ueki, Masahide Ebi, Naotaka Ogasawara, Toyonori Tsuzuki, Kenji Kasai, and et al. 2022. "The Complete Loss of p53 Expression Uniquely Predicts Worse Prognosis in Colorectal Cancer" International Journal of Molecular Sciences 23, no. 6: 3252. https://doi.org/10.3390/ijms23063252