Y Chromosome Loss Is a Frequent Event in Barrett’s Adenocarcinoma and Associated with Poor Outcome
Abstract
:1. Introduction
2. Results
2.1. Patient Samples and Correlation with Clinical Data
2.2. Y Chromosome Status in Cell Lines
2.3. Y Chromosome Status in the Patients’ Cohort
2.4. Heterogeneity of the Y Chromosome Status
2.5. Y Chromosome Status and Correlation with Immunohistochemical and Molecular Markers
2.6. LoY Correlation to Patients’ Outcome
3. Discussion
4. Materials and Methods
4.1. Patients and Tumor Samples
4.2. Cell Culture
4.3. Formalin-Fixation and Paraffin-Embedding of Cell Line Pellets
4.4. TMA Construction
4.5. Fluorescence In Situ Hybridization
4.6. Analysis of Heterogeneity of Y Chromosome Status
4.7. Immunohistochemistry
4.8. Data Analysis and Statistics
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Cliniopathological Parameter | Y Chromosome | |||||||
---|---|---|---|---|---|---|---|---|
Total | Loss | Presence | p Value | |||||
age group | <65 yrs | 210 | 52.8% | 117 | 56.0% | 93 | 44.0% | |
>65 yrs | 190 | 47.2% | 91 | 47.9% | 99 | 52.1% | 0.124 | |
tumor stage | pT1/2 | 109 | 27.4% | 52 | 48.6% | 56 | 51.4% | |
pT3/4 | 289 | 72.6% | 157 | 54.3% | 132 | 45.7% | 0.314 | |
lymph node metastasis | pN0 | 159 | 39.9% | 68 | 42.8% | 91 | 57.2% | |
pN+ | 239 | 60.1% | 142 | 59.4% | 97 | 40.6% | 0.001 | |
grading | G1 | 4 | 1.4% | 0 | 0.0% | 4 | 100.0% | |
G2 | 164 | 56.0% | 70 | 48.5% | 85 | 51.5% | ||
G3 | 123 | 42.3% | 73 | 59.3% | 50 | 40.7% | 0.031 | |
neoadjuvant treatment | no | 177 | 44.3% | 87 | 49.2% | 90 | 50.8% | |
yes | 223 | 55.7% | 123 | 55.2% | 100 | 44.8% | 0.268 | |
TP53 | wildtype | 122 | 41.5% | 53 | 43.4% | 69 | 56.6% | |
mutation | 172 | 58.5% | 106 | 61.6% | 66 | 38.4% | 0.003 | |
KRAS | negative | 318 | 81.3% | 159 | 50.0% | 159 | 50.0% | |
positive | 73 | 18.7% | 50 | 68.5% | 23 | 31.5% | 0.004 | |
HER2/neu | negative | 247 | 87.0% | 130 | 52.6% | 117 | 47.4% | |
positive | 37 | 13.0% | 22 | 59.5% | 15 | 40.5% | 0.483 | |
ARID1a | loss | 40 | 10.4% | 15 | 37.5% | 25 | 62.5% | |
presence | 343 | 89.6% | 188 | 54.8% | 155 | 45.2% | 0.045 | |
BRG1 | loss | 16 | 4.1% | 5 | 31.3% | 11 | 68.8% | |
presence | 371 | 95.9% | 202 | 54.4% | 169 | 45.6% | 0.078 | |
GATA6 | negative | 340 | 89.5% | 175 | 51.5% | 165 | 48.5% | |
positive | 40 | 10.5% | 23 | 57.5% | 17 | 42.5% | 0.507 | |
PIK3CA | negative | 335 | 94.1% | 181 | 54.0% | 154 | 46.0% | |
positive | 21 | 5.9% | 8 | 38.1% | 13 | 61.9% | 0.180 | |
CD3 infiltrating cells | low | 203 | 70.2% | 112 | 55.2% | 91 | 44.8% | 0.699 |
high | 86 | 29.8% | 45 | 52.3% | 41 | 47.7% | ||
LAG3 | negative | 290 | 93.9% | 159 | 54.8% | 131 | 45.2% | |
positive | 19 | 6.1% | 5 | 26.3% | 14 | 73.7% | 0.018 |
Clinicopathological Parameter | Hazard Ratio | 95% Confidence Interval | p Value | ||
---|---|---|---|---|---|
lower | upper | ||||
age group | <65 yrs. vs. >65 yrs | 1.435 | 0.978 | 2.105 | 0.065 |
tumor stage | pT1/2 vs. pT3/4 | 1.195 | 0.704 | 2.027 | 0.51 |
lymph node metastasis | pN0 vs. pN+ | 2.877 | 1.839 | 4.502 | <0.001 |
grading | G1 vs. G2/3 | 1.572 | 1.082 | 2.284 | 0018 |
TP53 | wildtype vs. mutation | 1.120 | 0.756 | 1.658 | 0.573 |
LoY | presence vs. loss | 1.835 | 2.725 | 1.233 | 0.003 |
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Loeser, H.; Wölwer, C.B.; Alakus, H.; Chon, S.-H.; Zander, T.; Buettner, R.; Hillmer, A.M.; Bruns, C.J.; Schroeder, W.; Gebauer, F.; et al. Y Chromosome Loss Is a Frequent Event in Barrett’s Adenocarcinoma and Associated with Poor Outcome. Cancers 2020, 12, 1743. https://doi.org/10.3390/cancers12071743
Loeser H, Wölwer CB, Alakus H, Chon S-H, Zander T, Buettner R, Hillmer AM, Bruns CJ, Schroeder W, Gebauer F, et al. Y Chromosome Loss Is a Frequent Event in Barrett’s Adenocarcinoma and Associated with Poor Outcome. Cancers. 2020; 12(7):1743. https://doi.org/10.3390/cancers12071743
Chicago/Turabian StyleLoeser, Heike, Christina B. Wölwer, Hakan Alakus, Seung-Hun Chon, Thomas Zander, Reinhard Buettner, Axel M. Hillmer, Christiane J. Bruns, Wolfgang Schroeder, Florian Gebauer, and et al. 2020. "Y Chromosome Loss Is a Frequent Event in Barrett’s Adenocarcinoma and Associated with Poor Outcome" Cancers 12, no. 7: 1743. https://doi.org/10.3390/cancers12071743