BACKGROUND Lynch syndrome(LS),an autosomal dominant genetic disorder,is distinguished by germline mutations in the DNA mismatch repair genes,including MLH1.These mutations confer an elevated risk for the development o...BACKGROUND Lynch syndrome(LS),an autosomal dominant genetic disorder,is distinguished by germline mutations in the DNA mismatch repair genes,including MLH1.These mutations confer an elevated risk for the development of colorectal cancer(CRC)and an array of other malignancies.Timely detection,facilitated by genetic profiling and stringent molecular surveillance,is crucial.It enables the implementation of customized therapeutic strategies,which have the potential to markedly enhance patient outcomes.Despite its significant public health impact,LS is frequently underdiagnosed,underscoring the necessity for increased vigilance and the adoption of precision medicine tactics.CASE SUMMARY This case presentation focuses on a 54-year-old male patient with a strong familial predisposition to colon cancer,who was identified to have LS-associated multiple colorectal neoplasms.Utilizing a comprehensive,multidisciplinary therapeutic strategy that encompassed precision medicine,immunotherapy with pembrolizumab,and stringent molecular residual disease monitoring,we effectively managed his advanced CRC.This tailored approach led to the achievement of sustained clinical remission exceeding 30 months,illustrating the promise of personalized treatment protocols in optimizing outcomes for individuals with LS and associated colorectal malignancies.CONCLUSION A synergistic,multidisciplinary approach is essential for managing LS-associated CRC,advocating for personalized care pathways in precision medicine.展开更多
BACKGROUND Hereditary factors are more prevalent in early-onset colorectal cancers(EOCRC)etiology.Lynch syndrome(LS)is the most common hereditary colorectal cancer(CRC)syndrome that results from mutations in DNA misma...BACKGROUND Hereditary factors are more prevalent in early-onset colorectal cancers(EOCRC)etiology.Lynch syndrome(LS)is the most common hereditary colorectal cancer(CRC)syndrome that results from mutations in DNA mismatch repair(MMR)genes.This phenomenon is defined as microsatellite instability(MSI).Immunohistochemistry(IHC)is a widely used,practical,and cost-effective method for the screening of MSI.However,using IHC alone may be insufficient to identify patients with MSI and LS.AIM To determine the clinicopathological features in EOCRC,IHC performance,and the frequency of genetic testing for EOCRC patients.METHODS A retrospective review was conducted on patients with CRC aged≤50 years who underwent surgery at our center between January 2014 and July 2021.MMR proteins were screened using IHC.Of the 131 patients included,IHC was performed on 130.Patients were classified as MSI or microsatellite-stable(MSS),and their features were compared.Additionally,data from patients who received genetic counseling were analyzed.RESULTS Thirty patients with MSI were designated as group 1,whereas 100 with MSS were defined as group 2.The mean age in group 1 was the lowest(median age:42 vs 46,P<0.05).Group 1 exhibited a higher frequency of tumors in the right colon and a lower frequency in the rectum.Lymph node involvement and distant metastases were less common in group 1,and in group 2,tumors were generally diagnosed at a more advanced stage.Genetic testing was performed in 53 patients(40%),with a definitive LS diagnosis established in 13/17 patients(76.4%)in group 1 and 1/36(2.7%)patients in group 2,resulting in a total of 14 patients(26.4%)with confirmed LS.CONCLUSION MSI tumors show a better prognosis.IHC is very effective for screening MSI,but may not be sufficient alone.Low genetic counseling rates highlight the need for hospital-based surveillance programs.展开更多
Lynch syndrome(LS)is the most common hereditary colorectal cancer(CRC)predisposition syndrome,characterized by a high mutational burden and microsatellite instability-high(MSI-H)tumors.Immunology of LS-associated CRC(...Lynch syndrome(LS)is the most common hereditary colorectal cancer(CRC)predisposition syndrome,characterized by a high mutational burden and microsatellite instability-high(MSI-H)tumors.Immunology of LS-associated CRC(LS-CRC)is unique,with significant implications for treatment.Despite well-established knowledge of LS immunology,immunotherapy dose and treatment response can vary significantly based on local tumor immunity and specific germline pathogenic variant of LS genes.This variability necessitates tailored surveillance strategies and new personalised immunotherapy approaches for LS patients.LS-CRC often benefits from immunotherapy due to the distinct tumor microenvironment(TME)and the variety of tumor infiltrating lymphocytes(TILs).This perspective discusses a novel approach of analysing spatial TILs at a single-cell level using tumor whole slide images(WSIs)that accounts for the distinct TME of LS-CRC.By emphasizing the necessity of personalized medicine in hereditary cancer syndromes,the future research and clinical practices that enhance patient outcomes through precision oncology is inspired.展开更多
Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations ...Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations in DNA mismatch repair(MMR)genes,including MLH1,MSH2,MSH6 and PMS2.These mutations lead to microsatellite instability(MSI)and defective DNA repair mechanisms,resulting in increased cancer risk.Early detection of LS is crucial for effective management and cancer prevention.Endoscopic surveillance,particularly regular colonoscopy,is recommended for individuals with LS to detect CRC at early stages.Additionally,universal screening of CRC for MMR deficiency can help identify at-risk individuals.Genetic counseling plays a valuable role in LS by guiding patients and their families in understanding the genetic basis,making informed decisions regarding surveillance and prevention,and offering reproductive options to reduce the transmission of pathogenic variants of the offspring.The aim of this review is to outline current strategies for the diagnosis,surveillance,and management of LS,with a focus on the role of genetic counseling,endoscopic screening,and emerging therapeutic approaches to mitigate cancer risk in affected individuals.展开更多
基金Supported by the National Natural Science Foundation of China,No.81972790the Natural Science Foundation of Gansu Province,China,No.22JR5RA004.
文摘BACKGROUND Lynch syndrome(LS),an autosomal dominant genetic disorder,is distinguished by germline mutations in the DNA mismatch repair genes,including MLH1.These mutations confer an elevated risk for the development of colorectal cancer(CRC)and an array of other malignancies.Timely detection,facilitated by genetic profiling and stringent molecular surveillance,is crucial.It enables the implementation of customized therapeutic strategies,which have the potential to markedly enhance patient outcomes.Despite its significant public health impact,LS is frequently underdiagnosed,underscoring the necessity for increased vigilance and the adoption of precision medicine tactics.CASE SUMMARY This case presentation focuses on a 54-year-old male patient with a strong familial predisposition to colon cancer,who was identified to have LS-associated multiple colorectal neoplasms.Utilizing a comprehensive,multidisciplinary therapeutic strategy that encompassed precision medicine,immunotherapy with pembrolizumab,and stringent molecular residual disease monitoring,we effectively managed his advanced CRC.This tailored approach led to the achievement of sustained clinical remission exceeding 30 months,illustrating the promise of personalized treatment protocols in optimizing outcomes for individuals with LS and associated colorectal malignancies.CONCLUSION A synergistic,multidisciplinary approach is essential for managing LS-associated CRC,advocating for personalized care pathways in precision medicine.
文摘BACKGROUND Hereditary factors are more prevalent in early-onset colorectal cancers(EOCRC)etiology.Lynch syndrome(LS)is the most common hereditary colorectal cancer(CRC)syndrome that results from mutations in DNA mismatch repair(MMR)genes.This phenomenon is defined as microsatellite instability(MSI).Immunohistochemistry(IHC)is a widely used,practical,and cost-effective method for the screening of MSI.However,using IHC alone may be insufficient to identify patients with MSI and LS.AIM To determine the clinicopathological features in EOCRC,IHC performance,and the frequency of genetic testing for EOCRC patients.METHODS A retrospective review was conducted on patients with CRC aged≤50 years who underwent surgery at our center between January 2014 and July 2021.MMR proteins were screened using IHC.Of the 131 patients included,IHC was performed on 130.Patients were classified as MSI or microsatellite-stable(MSS),and their features were compared.Additionally,data from patients who received genetic counseling were analyzed.RESULTS Thirty patients with MSI were designated as group 1,whereas 100 with MSS were defined as group 2.The mean age in group 1 was the lowest(median age:42 vs 46,P<0.05).Group 1 exhibited a higher frequency of tumors in the right colon and a lower frequency in the rectum.Lymph node involvement and distant metastases were less common in group 1,and in group 2,tumors were generally diagnosed at a more advanced stage.Genetic testing was performed in 53 patients(40%),with a definitive LS diagnosis established in 13/17 patients(76.4%)in group 1 and 1/36(2.7%)patients in group 2,resulting in a total of 14 patients(26.4%)with confirmed LS.CONCLUSION MSI tumors show a better prognosis.IHC is very effective for screening MSI,but may not be sufficient alone.Low genetic counseling rates highlight the need for hospital-based surveillance programs.
文摘Lynch syndrome(LS)is the most common hereditary colorectal cancer(CRC)predisposition syndrome,characterized by a high mutational burden and microsatellite instability-high(MSI-H)tumors.Immunology of LS-associated CRC(LS-CRC)is unique,with significant implications for treatment.Despite well-established knowledge of LS immunology,immunotherapy dose and treatment response can vary significantly based on local tumor immunity and specific germline pathogenic variant of LS genes.This variability necessitates tailored surveillance strategies and new personalised immunotherapy approaches for LS patients.LS-CRC often benefits from immunotherapy due to the distinct tumor microenvironment(TME)and the variety of tumor infiltrating lymphocytes(TILs).This perspective discusses a novel approach of analysing spatial TILs at a single-cell level using tumor whole slide images(WSIs)that accounts for the distinct TME of LS-CRC.By emphasizing the necessity of personalized medicine in hereditary cancer syndromes,the future research and clinical practices that enhance patient outcomes through precision oncology is inspired.
文摘Lynch syndrome(LS),also known as hereditary non-polyposis colorectal cancer(HNPCC),is an inherited condition associated with a higher risk of colorectal cancer(CRC)and other cancers.It is caused by germline mutations in DNA mismatch repair(MMR)genes,including MLH1,MSH2,MSH6 and PMS2.These mutations lead to microsatellite instability(MSI)and defective DNA repair mechanisms,resulting in increased cancer risk.Early detection of LS is crucial for effective management and cancer prevention.Endoscopic surveillance,particularly regular colonoscopy,is recommended for individuals with LS to detect CRC at early stages.Additionally,universal screening of CRC for MMR deficiency can help identify at-risk individuals.Genetic counseling plays a valuable role in LS by guiding patients and their families in understanding the genetic basis,making informed decisions regarding surveillance and prevention,and offering reproductive options to reduce the transmission of pathogenic variants of the offspring.The aim of this review is to outline current strategies for the diagnosis,surveillance,and management of LS,with a focus on the role of genetic counseling,endoscopic screening,and emerging therapeutic approaches to mitigate cancer risk in affected individuals.
