Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case report
Abstract Background Multiple primary malignancies are rare in cancer patients, and risk factors may include genetics, viral infection, smoking, radiation, and other environmental factors. Lynch syndrome (LS) is the most prevalent form of hereditary predisposition to double primary colorectal and end...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
|
| Series: | Diagnostic Pathology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13000-024-01447-8 |
| _version_ | 1797276056938348544 |
|---|---|
| author | Tiansong Zhang Xiaoqiang Huang Wenjie Liu Xiulan Ling Zhenping Su Mengwei Huang Shuanlong Che |
| author_facet | Tiansong Zhang Xiaoqiang Huang Wenjie Liu Xiulan Ling Zhenping Su Mengwei Huang Shuanlong Che |
| author_sort | Tiansong Zhang |
| collection | DOAJ |
| description | Abstract Background Multiple primary malignancies are rare in cancer patients, and risk factors may include genetics, viral infection, smoking, radiation, and other environmental factors. Lynch syndrome (LS) is the most prevalent form of hereditary predisposition to double primary colorectal and endometrial cancer in females. LS, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a common autosomal dominant condition. Pathogenic germline variants in the DNA mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6, and PMS2, and less frequently, deletions in the 3’ end of EPCAM cause LS. It manifested itself as loss of MMR nuclear tumor staining (MMR protein deficient, dMMR). Case presentation This case study describes a double primary carcinoma in a 49-year-old female. In June 2022, the patient was diagnosed with highly to moderately differentiated endometrioid adenocarcinoma. The patient’s mother died of esophageal cancer at age 50, and the father died of undefined reasons at age 70. Immunohistochemical stainings found ER (++), PR (++), P53 (+), MSH2 (-), MSH6 (+), MLH1 (+), and PMS2 (+). MMR gene sequencing was performed on endometrial tumor and peripheral blood samples from this patient. The patient carried two pathogenic somatic mutations in the endometrial tumor, MSH6 c.3261dupC (p.Phe1088LeufsTer5) and MSH2 c.445_448dup (p.Val150fs), in addition to a rare germline mutation MSH6 c.133G > C (p.Gly45Arg). Two years ago, the patient was diagnosed with moderately differentiated adenocarcinoma in the left-half colon. Immunohistochemical stainings found MSH2(-), MSH6(+), MLH1(+), and PMS2(+) (data not shown). Conclusions In the case of a patient with double primary EC and CRC, a careful evaluation of the IHC and the genetic data was presented. The patient carried rare compound heterozygous variants, a germline missense mutation, and a somatic frameshift mutation of MSH6, combined with a novel somatic null variant of MSH2. Our study broadened the variant spectrum of double primary cancer and provided insight into the molecular basis for abnormal MSH2 protein loss and double primary carcinoma. |
| first_indexed | 2024-03-07T15:22:51Z |
| format | Article |
| id | doaj.art-534f5e82f93f4ec5b034a2ea200c8f07 |
| institution | Directory Open Access Journal |
| issn | 1746-1596 |
| language | English |
| last_indexed | 2024-03-07T15:22:51Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Diagnostic Pathology |
| spelling | doaj.art-534f5e82f93f4ec5b034a2ea200c8f072024-03-05T17:30:30ZengBMCDiagnostic Pathology1746-15962024-01-011911810.1186/s13000-024-01447-8Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case reportTiansong Zhang0Xiaoqiang Huang1Wenjie Liu2Xiulan Ling3Zhenping Su4Mengwei Huang5Shuanlong Che6Department of Obstetrics and Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityGuangzhou KingMed Center for Clinical Laboratory Co. LtdDepartment of Obstetrics and Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityMeizhou Maternal and Child Health Care HospitalShenzhen KingMed Medical LaboratoryMeizhou Maternal and Child Health Care HospitalGuangzhou KingMed Center for Clinical Laboratory Co. LtdAbstract Background Multiple primary malignancies are rare in cancer patients, and risk factors may include genetics, viral infection, smoking, radiation, and other environmental factors. Lynch syndrome (LS) is the most prevalent form of hereditary predisposition to double primary colorectal and endometrial cancer in females. LS, also known as hereditary nonpolyposis colorectal cancer (HNPCC), is a common autosomal dominant condition. Pathogenic germline variants in the DNA mismatch repair (MMR) genes, namely MLH1, MSH2, MSH6, and PMS2, and less frequently, deletions in the 3’ end of EPCAM cause LS. It manifested itself as loss of MMR nuclear tumor staining (MMR protein deficient, dMMR). Case presentation This case study describes a double primary carcinoma in a 49-year-old female. In June 2022, the patient was diagnosed with highly to moderately differentiated endometrioid adenocarcinoma. The patient’s mother died of esophageal cancer at age 50, and the father died of undefined reasons at age 70. Immunohistochemical stainings found ER (++), PR (++), P53 (+), MSH2 (-), MSH6 (+), MLH1 (+), and PMS2 (+). MMR gene sequencing was performed on endometrial tumor and peripheral blood samples from this patient. The patient carried two pathogenic somatic mutations in the endometrial tumor, MSH6 c.3261dupC (p.Phe1088LeufsTer5) and MSH2 c.445_448dup (p.Val150fs), in addition to a rare germline mutation MSH6 c.133G > C (p.Gly45Arg). Two years ago, the patient was diagnosed with moderately differentiated adenocarcinoma in the left-half colon. Immunohistochemical stainings found MSH2(-), MSH6(+), MLH1(+), and PMS2(+) (data not shown). Conclusions In the case of a patient with double primary EC and CRC, a careful evaluation of the IHC and the genetic data was presented. The patient carried rare compound heterozygous variants, a germline missense mutation, and a somatic frameshift mutation of MSH6, combined with a novel somatic null variant of MSH2. Our study broadened the variant spectrum of double primary cancer and provided insight into the molecular basis for abnormal MSH2 protein loss and double primary carcinoma.https://doi.org/10.1186/s13000-024-01447-8Double primary carcinomaDeficient mismatch repair geneNovel mutationLynch-Like syndrome |
| spellingShingle | Tiansong Zhang Xiaoqiang Huang Wenjie Liu Xiulan Ling Zhenping Su Mengwei Huang Shuanlong Che Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case report Diagnostic Pathology Double primary carcinoma Deficient mismatch repair gene Novel mutation Lynch-Like syndrome |
| title | Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case report |
| title_full | Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case report |
| title_fullStr | Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case report |
| title_full_unstemmed | Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case report |
| title_short | Rare germline mutation and MSH2-&MSH6 + expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma: a case report |
| title_sort | rare germline mutation and msh2 msh6 expression in a double primary carcinoma of colorectal carcinoma and endometrial carcinoma a case report |
| topic | Double primary carcinoma Deficient mismatch repair gene Novel mutation Lynch-Like syndrome |
| url | https://doi.org/10.1186/s13000-024-01447-8 |
| work_keys_str_mv | AT tiansongzhang raregermlinemutationandmsh2msh6expressioninadoubleprimarycarcinomaofcolorectalcarcinomaandendometrialcarcinomaacasereport AT xiaoqianghuang raregermlinemutationandmsh2msh6expressioninadoubleprimarycarcinomaofcolorectalcarcinomaandendometrialcarcinomaacasereport AT wenjieliu raregermlinemutationandmsh2msh6expressioninadoubleprimarycarcinomaofcolorectalcarcinomaandendometrialcarcinomaacasereport AT xiulanling raregermlinemutationandmsh2msh6expressioninadoubleprimarycarcinomaofcolorectalcarcinomaandendometrialcarcinomaacasereport AT zhenpingsu raregermlinemutationandmsh2msh6expressioninadoubleprimarycarcinomaofcolorectalcarcinomaandendometrialcarcinomaacasereport AT mengweihuang raregermlinemutationandmsh2msh6expressioninadoubleprimarycarcinomaofcolorectalcarcinomaandendometrialcarcinomaacasereport AT shuanlongche raregermlinemutationandmsh2msh6expressioninadoubleprimarycarcinomaofcolorectalcarcinomaandendometrialcarcinomaacasereport |