Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients and Clinical Variables
2.2. MultiGene Next Generation Sequencing Test
2.3. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | n (%) |
---|---|
Age (years), median (range) | 52 (23–84) |
Histology | |
Endometrioid | 161 (78.9%) |
Serous | 17 (8.3%) |
Clear cell | 3 (1.5%) |
Mixed | 6 (2.9%) |
Neuroendocrine | 2 (1.0%) |
Mesonephric | 1 (0.5%) |
Dedifferentiated | 5 (2.5%) |
Carcinosarcoma | 5 (2.5%) |
Sarcoma | 4 (2.0%) |
Tumor location | |
Uterine corpus | 172 (84.3%) |
Lower uterine segment | 32 (15.7%) |
FIGO stage | |
I | 140 (68.6%) |
II | 14 (6.9%) |
III | 39 (19.1%) |
IV | 11 (5.4%) |
Other LS-associated cancers * | |
Yes | 84 (41.2%) |
No | 120 (58.8%) |
Family history ** of LS-associated cancers | |
Yes | 114 (55.9%) |
No | 90 (44.1%) |
Met the Amsterdam II criteria | |
Yes | 26 (12.7%) |
No | 178 (87.3%) |
Immunohistochemistry of MLH1/MSH2/MSH6/PMS2 | |
Tested | 133 |
Loss of expression of at least one | 57 (42.9%) |
Intact expression of all four | 76 (57.1%) |
Microsatellite instability test | |
Tested | 96 |
Microsatellite instability-high | 22 (22.9%) |
Microsatellite stable or microsatellite instability-low | 74 (77.1%) |
Case | Age | Gene | Mutation | Histology | Tumor Location | Family History of Cancers | Amsterdam II Criteria |
---|---|---|---|---|---|---|---|
YMCLynch009 | 46 | MLH1 | c.1489dup | Endometrioid | UC | C (mother, sister) | Yes |
YMCLynch006 * | 39 | MLH1 | c.1758dup | Endometrioid | LUS | EM (sister), C (uncle, nephew), S (mother, uncle) | Yes |
YMCLynch011 * | 41 | MLH1 | c.1758dup | Endometrioid | UC | EM (sister), C (uncle, nephew), S (mother, uncle) | Yes |
YMCLynch021 | 56 | MLH1 | c.1758dup | Endometrioid | UC | C (mother), GB (brother) | Yes |
YMCLynch104 | 53 | MLH1 | c.1758dup | Endometrioid | UC | P (mother), C (brother, aunt) | Yes |
CHALynch002 | 53 | MLH1 | c.1878_1881del | Endometrioid | UC | EM (sister), GB (sister) | No |
YMCLynch008 | 33 | MLH1 | c.2206G > T | Endometrioid | UC | C (father, brother) | Yes |
YMCLynch016 | 53 | MLH1 | c.306 + 1G > A | Endometrioid | UC | S (mother), Sm (brother) | Yes |
YMCLynch005 | 44 | MLH1 | c.440_441insT | Serous | UC | C (sister), GB (mother), S (father) | Yes |
YMCLynch028 | 40 | MLH1 | c.493del | Endometrioid | UC | C (father, grandfather) | Yes |
YMCLynch020 | 38 | MLH1 | c.1036C > T | Endometrioid | UC | None | No |
YMCLynch034 | 34 | MLH1 | c.790 + 1G > A | Endometrioid | LUS | C (father, aunt) | Yes |
YMCLynch022 | 65 | MSH2 | c.1276 + 1G > A | Endometrioid | UC | C (brother) | No |
SSCHLynch031 | 53 | MSH2 | c.187delG | Endometrioid | UC | None | No |
YMCLynch024 | 48 | MSH2 | c.792 + 1del | Endometrioid | UC | Es (father) | No |
YMCLynch017 | 49 | MSH2 | c.942 + 3A > T | Endometrioid | LUS | C (father, brother), S (uncle) | Yes |
YMCLynch003 | 43 | MSH2 | c.942 + 3A > T | Endometrioid | UC | C (father) | No |
CHALynch006 | 48 | MSH2 | c.1705_1706delGA | Endometrioid | UC | S (brother1, brother 2), H (father) | Yes |
CHALynch008 | 38 | MSH6 | c.3261dupC | Endometrioid | UC | None | No |
YMCLynch018 | 71 | MSH6 | c.3226C > T | Endometrioid | UC | C (brother), RC (brother) | No |
CHALynch011 # | 53 | MSH6 | c.3261dupC | Neuroendocrine | UC | C (sister, brother, sister 2), S (brother 1, brother 2, sister) | Yes |
CHALynch003 # | 61 | MSH6 | c.3261dupC | Serous | UC | C (sister, brother, sister 2), S (brother 1, brother 2, sister) | Yes |
CHALynch012 ** | 56 | MSH6 | c.3539C > G | Dedifferentiated | UC | C (father), EM (daughter) | Yes |
YMCLynch027 ## | 37 | MSH6 | c.1295T > C | Endometrioid | UC | Ov (mother), EM (sister) | Yes |
YMCLynch012 ## | 45 | MSH6 | c.1295T > C | Endometrioid | UC | Ov (mother), EM (sister) | Yes |
YMCLynch015 | 70 | MSH6 | c.3489dup | Endometrioid | LUS | EM (sister), C (brother), Th (son) | No |
YMCLynch030 | 48 | MSH6 | c.3844del | Endometrioid | LUS | C (mother), Es (father), S (uncle 1), L (uncle 2) | Yes |
CHALynch013 ** | 30 | MSH6 | c.3539C > G | Mixed | UC | C (grandfather), EM (mother) | Yes |
CHALynch015 | 54 | PMS2 | c.1738A > T | Endometrioid | UC | None | No |
YMCLynch031 | 38 | PMS2 | c.2444C > T | Mixed | UC | C (uncle), H (father) | Yes |
Variables | Sporadic Cancer (n = 174) | Lynch Syndrome | p-Value |
---|---|---|---|
Age, median (range) | 53 (23–84) | 48 (30–71) | 0.045 |
Histology | 0.771 | ||
Endometrioid | 137 (78.7%) | 24 (80.0%) | |
Serous | 15 (8.6%) | 2 (6.7%) | |
Clear cell | 3 (1.7%) | 0 | |
Mixed | 4 (2.3%) | 2 (6.7%) | |
Neuroendocrine | 1 (0.6%) | 1 (3.3%) | |
Mesonephric | 1 (0.6%) | 0 | |
Dedifferentiated | 4 (2.3%) | 1 (3.3%) | |
Carcinosarcoma | 5 (2.9%) | 0 | |
Sarcoma | 4 (2.3%) | 0 | |
Tumor location | 0.586 | ||
Uterine corpus | 148 (85.1%) | 25 (83.3%) | |
Lower uterine segment | 26 (14.9%) | 5 (16.7%) | |
FIGO stage | 0.357 | ||
I | 121 (69.5%) | 19 (63.3%) | |
II | 13 (7.5%) | 1 (3.3%) | |
III | 30 (17.2%) | 9 (30.0%) | |
IV | 10 (5.7%) | 1 (3.3%) | |
Other LS-associated cancers * | 0.389 | ||
Yes | 69 (39.7%) | 15 (50%) | |
No | 105 (60.3%) | 15 (50.0%) | |
Family history ** of LS-associated cancers | 0.001 | ||
Yes | 88 (49.4%) | 26 (86.7%) | |
No | 86 (50.6%) | 4 (13.3%) | |
Met the Amsterdam II criteria | <0.001 | ||
Yes | 6 (3.5%) | 20 (66.7%) | |
No | 168 (96.5%) | 10 (33.3%) |
Variables | High-Penetrance Genes (MLH1/MSH2, n = 18) | Low-Penetrance Genes (MSH6/PMS2, n = 12) | p-Value |
---|---|---|---|
Age (median, range) | 47 (33–65) | 40 (30–71) | 0.407 |
Histology | 0.026 | ||
Endometrioid | 17 (94.4%) | 7 (58.3%) | |
Non-endometrioid | 1 (5.6%) | 5 (41.7%) | |
Tumor location | 0.660 | ||
Uterine corpus | 15 (83.3%) | 10 (83.3%) | |
Lower uterine segment | 3 (16.7%) | 2 (16.7%) | |
FIGO stage | 0.694 | ||
I/II | 11 (61.1%) | 9 (75.0%) | |
III/IV | 7 (38.9%) | 3 (25.0%) | |
Other LS-associated cancers | 0.264 | ||
Yes | 11 (61.1%) | 4 (33.3%) | |
No | 7 (38.9%) | 8 (66.7%) | |
Family history of LS-associated cancers | 1 | ||
Yes | 16 (88.9%) | 10 (83.3%) | |
No | 2 (11.1%) | 2 (16.7%) | |
Amsterdam II criteria | 1 | ||
Yes | 12 (66.7%) | 8 (66.7%) | |
No | 6 (33.3%) | 4 (33.3%) |
Ring et al. [26] | Levine et al. [27] | Karpel et al. [17] | Present Study | |
---|---|---|---|---|
N | 381 | 961 | 224 | 200 # |
Country | USA | USA | USA | Korea |
Year of publication | 2016 | 2021 | 2022 | 2022 |
Number of genes tested | 25 | 47 | N/A | 22 |
Age, median | 61 * | 62 | 57 | 52 |
Asian ethnicity | 14 (3.7%) | 9 (0.9%) | 25 (11.2%) | 200 (100%) |
Endometrioid histology | 289 (75.9%) | 819 (85.2%) | 148 (66.1%) | 161 (80.5%) |
Lynch syndrome genes | 22 (5.8%) | 29 (3.0)% | 21 (9.4%) | 26 (13.0%) |
MLH1 | 3 (13.6%) | 2 (6.9%) | 4 (19.0%) | 11 (42.3%) |
MSH2 | 5 (22.7%) | 6 (20.7%) | 5 (23.8%) | 6 (23.1%) |
MSH6 | 6 (27.3%) | 10 (34.5%) | 7 (33.3%) | 7 (26.9%) |
PMS2 | 6 (27.3%) | 11 (37.9%) | 4 (19.0%) | 2 (7.7%) |
EPCAM | 2 (9.1%) | 29 (3.0)% | 1 (4.8%) | |
Non-Lynch syndrome genes | 13 (3.4%) | 68 (7.1%) ** | 13 (5.8%) | 4 (2.0%) |
APC | 1 (7.7%) | 2 (15.4%) | ||
ATM | 1 (7.3%) | 2 (2.9%) | 2 (15.4%) | |
BARD1 | 1 (7.3%) | |||
BRCA1 | 1 (7.3%) | 4 (5.9%) | 1 (7.7%) | |
BRCA2 | 1 (7.3%) | 6 (8.8%) | 2 (15.4%) | 1 (25.0%) |
BRIP1 | 1 (7.3%) | 6 (8.8%) | 1 (25.0%) | |
CHEK2 | 4 (30.8%) | 17 (25.0%) | 6 (46.2%) | |
MUTYH | 15 (22.1%) | 1 (25.0%) | ||
NBN | 1 (7.3%) | 4 (5.9%) | ||
PTEN | 1 (7.3%) | |||
RAD50 | 1 (25.0%) | |||
RAD51C | 1 (7.3%) | 1 (1.5%) | 1 (7.7%) |
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Kim, Y.-N.; Kim, M.K.; Lee, Y.J.; Lee, Y.; Sohn, J.Y.; Lee, J.-Y.; Choi, M.C.; Kim, M.; Jung, S.G.; Joo, W.D.; et al. Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test. Cancers 2022, 14, 3406. https://doi.org/10.3390/cancers14143406
Kim Y-N, Kim MK, Lee YJ, Lee Y, Sohn JY, Lee J-Y, Choi MC, Kim M, Jung SG, Joo WD, et al. Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test. Cancers. 2022; 14(14):3406. https://doi.org/10.3390/cancers14143406
Chicago/Turabian StyleKim, Yoo-Na, Min Kyu Kim, Young Joo Lee, Youngeun Lee, Ji Yeon Sohn, Jung-Yun Lee, Min Chul Choi, Migang Kim, Sang Geun Jung, Won Duk Joo, and et al. 2022. "Identification of Lynch Syndrome in Patients with Endometrial Cancer Based on a Germline Next Generation Sequencing Multigene Panel Test" Cancers 14, no. 14: 3406. https://doi.org/10.3390/cancers14143406