Combined BRCA2 and MAGEC3 Expression Predict Outcome in Advanced Ovarian Cancers
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Ovarian Cancer Patients
2.2. Whole Tissue Sections
2.3. Tissue Microarray (TMA) Construction
2.4. Antibody Validation
2.5. Immunohistochemistry
2.6. Digital Image Analysis
2.7. Statistical Methods
3. Results
3.1. Validation of IHC Measurements of BRCA2 Protein Expression in Cancer Tissue
3.2. Clinical Characteristics of Ovarian Cancer Microarray Patient Population
3.3. BRCA2 Protein Shows a Weak Negative Correlation with MAGEC3 Expression in Ovarian Cancer Tumor Samples
3.4. MAGEC3 and BRCA2 Association with Prognosis in Epithelial Ovarian Cancer
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | MAGEloss | MAGEnormal | ||||
---|---|---|---|---|---|---|
All Ovary Patients | BRCA2exp(−) | BRCA2exp(+) | BRCA2exp(−) | BRCA2exp(+) | p-Value | |
n = 357 | n = 34 | n = 139 | n = 24 | n = 160 | ||
Age of Diagnosis (years) | 0.1 † | |||||
Mean (Range) | 63 (21–93) | 61 (21–85) | 63 (31–93) | 69 (47–89) | 63 (21–89) | |
Missing | 0 | 0 | 0 | 0 | 0 | |
Year of Diagnosis (n (%)) | <0.001 ‡ | |||||
Before 2006 | 177 (52.1) | 14 (43.8) | 104 (81.9) | 5 (21.7) | 54 (34.2) | |
After 2006 | 163 (47.9) | 18 (56.3) | 23 (18.1) | 18 (78.3) | 104 (65.8) | |
Missing | 17 | 2 | 12 | 1 | 2 | |
Race (n (%)) | ||||||
White | 334 (94.9) | 31 (94) | 130 (96.3) | 24 (100) | 149 (93.1) | 0.2 § |
Black or African American | 8 (2.3) | 1 (3) | 0 (0) | 0 (0) | 7 (4.4) | |
Other | 10 (2.8) | 1 (3) | 5 (3.7) | 0 (0) | 4 (2.5) | |
Missing | 5 | 1 | 4 | 0 | 0 | |
Hispanic (n (%)) | ||||||
No | 350 (99.4) | 34 (100) | 133 (99.3) | 24 (100) | 159 (99.4) | 0.9 § |
Yes | 2 (0.6) | 0 (0) | 1 (0.7) | 0 (0) | 1 (0.6) | |
Missing | 5 | 0 | 5 | 0 | 0 | |
Primary (n (%)) | ||||||
Ovary | 310 (88.1) | 27 (81.8) | 131 (94.9) | 16 (66.7) | 136 (86.6) | <0.001 ‡ |
Primary Peritoneal | 42 (11.9) | 6 (18.2) | 7 (5.1) | 8 (33.3) | 21 (13.4) | |
Missing | 5 | 1 | 1 | 0 | 3 | |
FIGO Stage (n (%)) | 0.6 ‡ | |||||
I/II/IIIA/B | 65 (18.5) | 8 (24.2) | 28 (20.6) | 4 (17.4) | 25 (15.7) | |
IIIC/IV | 286 (81.5) | 25 (75.8) | 108 (79.4) | 19 (82.6) | 134 (84.3) | |
Missing | 6 | 1 | 3 | 1 | 1 | |
Grade (n (%)) | 0.03 ‡ | |||||
Well/Moderately differentiated | 93 (26.5) | 5 (14.7) | 44 (32.6) | 2 (8.3) | 42 (26.6) | |
Poorly/Undifferentiated | 258 (73.5) | 29 (85.3) | 91 (67.4) | 22 (91.7) | 116 (73.4) | |
Missing | 6 | 0 | 4 | 0 | 2 | |
Histology (n (%)) | ||||||
Serous | 284 (79.6) | 17 (50) | 114 (82) | 20 (83.3) | 133 (83.1) | <0.001 ‡ |
Other Epithelial | 73 (20.4) | 17 (50) | 25 (18) | 4 (16.7) | 27 (16.9) | |
Missing | 0 | 0 | 0 | 0 | 0 | |
Cytoreduction (n (%)) | 0.09 ‡ | |||||
R0 | 98 (27.8) | 9 (28.1) | 41 (29.9) | 5 (20.8) | 43 (26.9) | |
Not R0 | 255 (72.2) | 23 (71.9) | 96 (70.1) | 19 (79.2) | 117 (73.1) | |
Missing | 4 | 2 | 2 | 0 | 0 | |
Platinum sensitivity (n (%)) | ||||||
Sensitive | 156 (55.5) | 9 (37.5) | 65 (55.1) | 11 (68.8) | 71 (57.7) | 0.8 ‡ |
Resistant | 125 (44.5) | 15 (62.5) | 53 (44.9) | 5 (31.3) | 52 (42.3) | |
Missing | 76 | 10 | 21 | 8 | 37 | |
Treatment Outcome (n (%)) | ||||||
Complete Response | 169 (57.5) | 9 (37.5) | 65 (55.1) | 9 (52.9) | 86 (63.7) | 0.2 ‡ |
Not Complete Response | 125 (42.5) | 15 (62.5) | 53 (44.9) | 8 (47.1) | 49 (36.3) | |
Missing | 63 | 10 | 21 | 7 | 25 |
Ovarian Cancer | Univariate Analysis (n = 357) † | Multivariate Analysis (n = 342) | |||||
---|---|---|---|---|---|---|---|
Covariate | Risk Level | Hazard Ratio | 95% CI | p-Value ‡ | Hazard Ratio | 95% CI | p-Value ‡ |
Age | +10 years | 1.3 | (1.18–1.42) | <0.001 | 1.32 | (1.19–1.46) | <0.001 |
Stage | I/II/IIIA/B | Reference | Reference | ||||
IIIC/IV | 3.45 | (2.4–4.96) | <0.001 | 3.28 | (2.05–5.26) | <0.001 | |
Grade | Well/Moderately differentiated | Reference | Reference | ||||
Poorly/Undifferentiated | 1.15 | (0.89–1.49) | 0.3 | 1.34 | (1.02–1.76) | 0.04 | |
Histology | Other Epithelial | Reference | Stratifier § | ||||
Serous | 1.17 | (0.87–1.57) | 0.3 | ||||
Cytoreduction | R0 | Reference | Stratifier § | ||||
Not R0 | 2.43 | (1.84–3.15) | <0.001 | ||||
MAGEC3 and | Loss~Exp(−) | Reference | Reference | ||||
BRCA2 | Normal~Exp(−) | 1.29 | (0.85–1.95) | 0.2 | 1.14 | (0.73–1.79) | 0.6 |
Loss~Exp(+) | 1.17 | (0.72–1.89) | 0.5 | 1 | (0.61–1.63) | 1 | |
Normal~Exp(+) | 1.16 | (0.91–1.49) | 0.2 | 1.14 | (0.88–1.48) | 0.3 |
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Omole, E.B.; Aijaz, I.; Ellegate, J., Jr.; Isenhart, E.; Desouki, M.M.; Mastri, M.; Humphrey, K.; Dougherty, E.M.; Rosario, S.R.; Nastiuk, K.L.; et al. Combined BRCA2 and MAGEC3 Expression Predict Outcome in Advanced Ovarian Cancers. Cancers 2022, 14, 4724. https://doi.org/10.3390/cancers14194724
Omole EB, Aijaz I, Ellegate J Jr., Isenhart E, Desouki MM, Mastri M, Humphrey K, Dougherty EM, Rosario SR, Nastiuk KL, et al. Combined BRCA2 and MAGEC3 Expression Predict Outcome in Advanced Ovarian Cancers. Cancers. 2022; 14(19):4724. https://doi.org/10.3390/cancers14194724
Chicago/Turabian StyleOmole, Emmanuel B., Iqbal Aijaz, James Ellegate, Jr., Emily Isenhart, Mohamed M. Desouki, Michalis Mastri, Kristen Humphrey, Emily M. Dougherty, Spencer R. Rosario, Kent L. Nastiuk, and et al. 2022. "Combined BRCA2 and MAGEC3 Expression Predict Outcome in Advanced Ovarian Cancers" Cancers 14, no. 19: 4724. https://doi.org/10.3390/cancers14194724