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Lynch syndrome (LS) is a common hereditary tumor syndrome. Gynecological malignancy is usually the first tumor of LS in women, and endometrial cancer (EC) is the most closely associated with LS. Most patients with LS are unaware of this risk, and it is possible to cause misdiagnosis. Thus, early diagnosis helps patients to start tumor surveillance timely, as well as a cascade of family surveillance. This paper reviews the progress of LS associated with EC.
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Objective:To study the clinical characteristics of Lynch syndrome-associated endometrial cancer in elderly patients and the relationship of the disease with MSH2 gene mutations in patients' families.Methods:Clinical data of 473 elderly patients with endometrial cancer admitted to our hospital between January 2016 and January 2021 were retrospectively analyzed.MSH2 gene mutations were detected and verified by DNA sequence analysis, real-time quantitative PCR and reverse transcription PCR.Patients were divided into a Lynch syndrome group and a non-Lynch syndrome group, and the clinicopathological features of the two groups were compared.Results:Of 473 endometrial carcinoma patients, 46(9.7%)had embryogenic mutations of the MMR gene and were diagnosed with Lynch syndrome, with 18, 6, 24 and 10 patients carrying MLH1, PMS2, MSH2 and MSH6 mutations, respectively.There were 3 mutations in the MSH2 gene, including exon 7 1380C>A, exon 12 2011A>G and exon 13 2756A→AC.The proportions of patients with G3 grade endometrioid adenocarcinoma, lower uterine segment involvement and a history of Lynch syndrome-associated malignant tumors in the Lynch syndrome group were significantly higher than those in the non-Lynch syndrome group( χ2=8.935, 8.303, 9.770, all P<0.05). Conclusions:Poorly differentiated endometrioid adenocarcinoma, predisposition to lower uterine segment involvement and familial inheritance are the main clinical manifestations of Lynch syndrome-associated endometrial carcinoma in elderly patients, with the most common mutations seen in the MSH2 gene.
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Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) is a type of inherited cancer syndrome with a genetic predisposition to different types of cancer. There is an increased predisposition to cancers in the endometrium, colon, stomach, ovary, uterus, skin, kidney, and brain in patients of Lynch syndrome. We are reporting a 48-year-old male who presented with a pea-sized growth in his left arm which was found to be sebaceoma on histopathology. On further detailed history, examination, and genetic study, it was proved to be a familial case of Lynch syndrome. The case is being reported to stress the importance of knowledge about clinical manifestation, associated neoplasms, and molecular genetic profile of Lynch syndrome which will enable physicians and pathologists to provide highly targeted surveillance and management for patients with high cancer risk.
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Context: Approximately 20%–30% of colon cancer cases have a hereditary basis. The genetic defect may involve mismatch repair (MMR) genes, which results in microsatellite instability (MSI). MMR-deficient colorectal cancer may occur due to germline mutation (Lynch syndrome) or be a sporadic one. A tumor's histological features, supported by a panel of immunohistochemistry stains, enables pathologists to assess the MMR status, which in turn has beneficial effects on clinical management. Aims: We aimed to show the relations between histopathological features identified during routine examinations and MMR genes' mutations. Methods and Material: We reviewed retrospectively the material of the Department of Pathology fulfilling the revised Bethesda Guidelines. Statistical Analysis Used: We used Chi-square test, Spearman test, and epidemiological analysis. Results: For the PMS2 gene, the positive predictive value (PPV) indicates that 91% of cases neither present any histological lesions nor have genetic abnormalities. The negative predictive value (NPV) indicates that only 50% of cases have both histological and genetic changes. For the MSH6 gene, the PPV indicates that 85% of tumors without specific histological features do not have genetic abnormalities. Conclusions: We advise universal staining for MLH1, MSH2, MSH6, and PMS2 in every newly diagnosed colon cancer, but due to costly analyses we suggest a protocol for the selection of cases for MMR examinations.
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Hereditary colorectal cancer accounts for approximately 5% of all colorectal cancer cases, mainly including familial adenomatous polyposis and Lynch syndrome. Total proctocolectomy plus ileal pouch-anal anastomosis and total colectomy plus ileorectal anastomosis are two major procedures for familial adenomatous polyposis, however, the exact impact of these two procedures on surgical efficacy, oncologic efficacy as well as functional results still remains uncertain. Segmental colectomy and total colectomy are two major procedures for Lynch syndrome, each of them both has advantages and disadvantages, and there still lacks a consensus about the optimal strategy because of the nature of retrospective study with a relatively insufficient evidence support. As a result, we would make a review about the current surgical treatment status and future perspectives of hereditary colorectal cancer.
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Humanos , Polipose Adenomatosa do Colo/cirurgia , Anastomose Cirúrgica/métodos , Colectomia , Neoplasias Colorretais Hereditárias sem Polipose/cirurgia , Proctocolectomia Restauradora/métodos , Estudos RetrospectivosRESUMO
The functional loss of the mismatch repair system is related to the occurrence of colorectal cancer. Some colorectal cancers have mismatch repair defects, however, the methylation of the MLH1 promoter cannot be detected, and germline mutations of the mismatch repair genes are not detected. Because this part of the group is very similar to Lynch syndrome, it is named Lynch-like syndrome. Lynch-like syndrome has certain genetic characteristics, but the pathogenesis has not been fully understood; and it cannot be simply classified as sporadic colorectal cancer or Lynch syndrome, and there is a lack of genetic knowledge and monitoring standards of these patients. This article introduces the progress of Lynch-like syndrome.
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About 1/3 of patients with colorectal cancer have a genetic background. Familial colorectal cancer type X refers to colorectal cancer clinically in line with Amsterdam criteria Ⅱ, but genetic testing of which does not show microsatellite instability or DNA mismatch repair gene mutations. Its tumor cell gene is microsatellite stable. Attention should be paid to the differen-tiation from Lynch syndrome. Familial colorectal cancer type X is highly heterogeneous, without unclear etiology so far. It is recommended to refer to sporadic colorectal cancer for diagnosis, treatment, follow-up and prevention. The authors introduce the diagnosis and treatment of a case of familial colorectal cancer type X, in order to provide references for clinical diagnosis of this disease.
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Abstract Introduction: Colorectal carcinoma is the third most prevalent neoplasm in the world, and the second cause of death by cancer. The most part of these neoplasms are sporadic by somatic mutations, but around 15% are hereditary, such as Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC). Despite being the same tumor, it has differences between these two contexts as well as different prognosis. In Lynch syndrome cases, the survival of these individuals was greater than that observed in sporadic cases. Methods: This review focuses on the different characteristics and development of colorectal carcinoma in sporadic and Lynch syndrome cases, in order to conclude what may motivate the greater survival in the tumors associated with this syndrome. Results: Although the histopathological features drive into a worse prognosis, the colorectal carcinoma in the Lynch Syndrome presents a greater survival comparing to sporadic colorectal carcinoma. Discussion: The greater survival in the colorectal carcinoma in the HNPCC compared to the sporadic carcinomas has been linked to factors such as high microsatellite instability, diploid predominance, earlier screening for colo-rectal carcinoma, deficient DNA repair mechanism, low p53 mutation rate, and presence of lymphoid aggregates involving the neoplasm. Conclusion: Further studies should be conducted to provide new insights about survival of colorectal carcinoma in Lynch syndrome, as well as the therapeutic alternatives for this neoplasia.
Resumo Introdução: O carcinoma colorretal é a terceira neoplasia mais prevalente no mundo, bem como a segunda causa de morte por câncer. A maioria destas neoplasias são esporádicas, devidas a mutações somáticas, mas cerca de 15% são hereditárias como a síndrome de Lynch ou Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Apesar de ser a mesma neoplasia, esta apresenta características clinico-patológicas e moleculares distintas, bem como diferentes prognósticos. Nos casos de síndrome de Lynch, a sobrevida parece ser maior quando comparada com os carcinomas esporádicos. Métodos: Realizamos uma revisão bibliográfica sobre as diferentes características e desenvolvimentos do carcinoma colorretal esporádico e no contexto da síndrome de Lynch, para concluir o que causa a maior sobrevida no caso das neoplasias associadas a esta síndrome. Resultados: Apesar das características histopatológicas apontarem para um pior prognóstico, o HNPCC apresenta uma maior sobrevida em relação ao carcinoma colorretal esporádico. Discussão: A maior sobrevivência nos carcinomas colorretais associados ao HNPCC em comparação com os carcinomas colorretais esporádicos tem sido atribuída a fatores como a elevada instabilidade microssatélite, a predominância diploide, a realização de rastreio para o carcinoma colorretal mais precoce, deficiente mecanismo de reparação de DNA, menor taxa de mutação da p53 e existência de agregados linfoides a envolver a neoplasia. Conclusão: Consideramos que deve ser encorajado o estudo mais aprofundado dos fatores que levam à maior sobrevida do carcinoma colorretal na síndrome de Lynch, bem como de alternativas terapêuticas para esta neoplasia.
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Neoplasias Colorretais , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologiaRESUMO
ABSTRACT Background: Colorectal cancer survival is better in hereditary nonpolyposis colorectal cancer patients than in sporadic colorectal cancer patients and even for hereditary nonpolyposis colorectal cancer with colorectal cancer is not consensual that extensive colectomy is preferable to partial colectomy. This study analyzes and compares the long-term results of these two groups of patients submitted to curative subtotal colectomy or total colectomy. Methods: Between 2002 and 2018, 68 patients with colorectal cancer without familial adenomatous polyposis were submitted to a total or subtotal colectomy in a single tertiary center. The patients were divided in two groups: hereditary nonpolyposis colorectal cancer patients (with Amsterdam criteria) and sporadic colorectal cancer patients (the others). The presence of Amsterdam criteria for hereditary nonpolyposis colorectal cancer and germline mutation for mismatch repair genes was confirmed by clinical records. Results and survival were analyzed following surgery. Results: We obtained a sporadic colorectal cancer group with 31 patients and a hereditary nonpolyposis colorectal cancer group with 37 patients. The two groups differ in age but not in gender, tumor stage or surgical morbidity. The overall survival and disease-free survival were good in both groups but even better for hereditary nonpolyposis colorectal cancer group with statistical significance when comparing the two groups. Conclusion: Total or subtotal colectomy for colorectal cancer provides a good survival. These surgical procedures should be considered the first option for colorectal cancer in young hereditary non polyposis colorectal cancer patients. In those cases, they provide good long-term results, avoiding the risk of metachronous colorectal cancer and the surveillance is restricted only to the remaining need for rectum.
RESUMO Introdução: A sobrevivência do cancro colorretal é melhor em pacientes com cancro colorretal hereditário não associado a polipose do que em pacientes com cancro colorretal esporádico. Mesmo em casos de cancro colorretal hereditário sem polipose, a preferência pela colectomia total em relação à parcial não é consensual na literatura. Este estudo analisa e compara os resultados a longo prazo destes dois grupos de pacientes submetidos à colectomia curativa subtotal ou total. Métodos: Entre 2002 e 2018, 68 pacientes com cancro colorretal sem polipose adenomatosa familiar foram submetidos a colectomia total ou subtotal em um único centro terciário. Os pacientes foram divididos em dois grupos: aqueles com cancro colorretal hereditário sem polipose (de acordo com os critérios de Amsterdão) e os com cancro colorretal esporádico (os demais). Os critérios de Amsterdão para cancro colorretal hereditário sem polipose e a presença de mutação germinativa para os genes de reparação de ADN foram confirmados por consulta dos registros clínicos. Os resultados e a sobrevivência foram analisados após a cirurgia. Resultados: No presente estudo, 31 pacientes foram incluídos no grupo de cancro colorretal esporádico e 37 no grupo de cancro colorretal hereditário sem polipose. Diferenças significativas foram observadas em relação à idade, mas não ao gênero, estadio do tumor ou morbilidade cirúrgica. A sobrevivência global e a sobrevivência livre de doença foram boas em ambos os grupos, mas os resultados foram ainda melhores no grupo de cancro colorretal hereditário sem polipose, com significado estatístico. Conclusão: A colectomia total ou a colectomia subtotal para o cancro colorretal proporcionam uma boa sobrevivência e devem ser consideradas a primeira opção de tratamento em pacientes jovens com cancro colorretal hereditário sem polipose. Nestes pacientes, uma cirurgia cólica mais extensa permite a obtenção de bons resultados a longo prazo; reduz o risco de cancro colorretal metácrono e restringe a vigilância endoscópica ao reto remanescente.
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Humanos , Masculino , Feminino , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais Hereditárias sem Polipose , Colectomia , Colo/patologia , Reparo de Erro de Pareamento de DNARESUMO
Lynch syndrome (LS), an autosomal dominantly inherited disease previously known as hereditary non-polyposis colorectal cancer (HNPCC), leads to a high risk of colorectal cancer (CRC) as well as malignancy at certain sites including endometrium, ovary, stomach, and small bowel (Hampel et al., 2008; Lynch et al., 2009). Clinically, LS is considered the most common hereditary CRC-predisposing syndrome, accounting for about 3% of all CRC cases (Popat et al., 2005). LS is associated with mutations of DNA mismatch repair (MMR) genes such as MLH1, MSH2, MSH6, PMS2, and EPCAM (Ligtenberg et al., 2009; Lynch et al., 2009), which can trigger a high frequency of replication errors in both microsatellite regions and repetitive sequences in the coding regions of various cancer-related genes. Immunohistochemistry (IHC) tests followed by genetic analysis of these mutations play a significant role in diagnosis, treatment determination, and therapeutic response prediction of LS (Lynch et al., 2009; Alex et al., 2017; Ryan et al., 2017). Here, we report substitution of one base-pair in exon 1 of MLH3 (c.1397C>A) and a frameshift mutation in exon 19 of MLH1 (c.2250_2251ins AA) in a 43-year-old Chinese male with an LS pedigree.
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Adulto , Feminino , Humanos , Masculino , Povo Asiático/genética , China , Neoplasias Colorretais Hereditárias sem Polipose/genética , Éxons , Mutação da Fase de Leitura , Mutação em Linhagem Germinativa , Proteína 1 Homóloga a MutL/genética , Proteínas MutL/genética , LinhagemRESUMO
Lynch syndrome (LS), which is the most common hereditary colorectal cancer, accounts for about 3% of all colorectal cancers. However, due to its various clinical manifestations, it is difficult to be diagnosed. The diagnosis of LS requires comprehensive application of various screening criteria (such as the Amsterdam criteria, Bethesda criteria), predictive models, risk factors, immunohistochemistry test of mismatch repair (MMR) protein, microsatellite instability (MSI) detection, MLH1 methylation detection, BRAF gene mutation detection, germline gene mutation detection, and so on. LS can be diagnosed only after the identification of pathogenic germline mutation of MMR gene. The first-degree and second-degree relatives of LS patients are recommended to be tested for the identified mutant gene. For LS patients and gene mutation carriers, LS associated cancer can be detected early or even prevented by monitoring and preventive surgery. Reproductive techniques can be used to prevent this disease from being passed down to the next generation.
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Esta revisión tiene como objetivo dar a conocer los aspectos genéticos, clínicos y diagnósticos del síndrome de Lynch, además de brindar la información más relevante acerca de la asesoría genética en estos pacientes y las recomendaciones actuales para su seguimiento.
This review aims to present the genetic, clinical and diagnostic aspects of Lynch syndrome, as well as providing the most relevant information about genetic counseling in these patients and the current recommendations for their surveillance.
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História do Século XIX , História do Século XX , Humanos , Neoplasias Colorretais Hereditárias sem Polipose , Algoritmos , Síndromes Neoplásicas Hereditárias/diagnóstico , DNA de Neoplasias/genética , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/história , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Biomarcadores Tumorais , Risco , Endoscopia Gastrointestinal , Medição de Risco , Heterogeneidade Genética , Penetrância , Diagnóstico Diferencial , Genes Neoplásicos , Instabilidade de Microssatélites , Reparo de Erro de Pareamento de DNA/genética , Estudos de Associação Genética , Aconselhamento Genético , Modelos GenéticosRESUMO
Hereditary colorectal cancer can be divded into two categories based on the presence or absence of polyps. The first category is characterized by the development of polyposis, which includes familial adenomatous polyposis (FAP); The second category is nonpolyposis colorectal cancer, which is represented by Lynch syndrome. "Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China" developed by the Genetics Group of the Committee of Colorectal Cancer, Chinese Anti-cancer Association, is composed of three sections, including hereditary nonpolyposis syndrome, polyposis syndrome as well as genetic evaluation of hereditary colorectal cancer. The consensus aims to provide recommendations on management of the respective hereditary syndromes in terms of definition, clinical and pathological features, diagnostic standards, treatment, and follow-ups. In addition to describing diagnostic and treatment strategies, prophylactic treatment as well as genetic screening and pedigree monitoring is highly recommended. Through the establishment of this expert consensus, we hope to promote better understanding of hereditary colorectal cancer for clinicians and encourage standardized treatment through multidisciplinery approaches, eventually improving clinical treatment and pedigree management of hereditary colorectal cancer in China.
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BACKGROUND: The phenotypic and genetic spectrum of Lynch syndrome (LS) seems to differ according to ethnicity. The aim of this study was to investigate the clinical, pathological, and genetic features of LS in a large sample of Korean patients. METHODS: We enrolled a total of 232 patients who fulfilled the revised Bethesda criteria (81%, 232/286) from 286 individuals who underwent genetic screening for LS (MLH1, MSH2, and MSH6 sequencing) in the Samsung Medical Center in Korea from 2004 to 2015. Histopathologic findings, microsatellite instability data, and clinical information were collected. RESULTS: We identified 61 different pathogenic or likely pathogenic variants (39 in MLH1, 20 in MSH2, and 2 in MSH6), including 4 novel variants, in 101 unrelated Korean patients (101/232, 44%). When multiple tumor manifestations in a single patient were individually considered, there were 285 cancers recorded from 232 cases. A diverse spectrum of tumors, including colorectal cancer, endometrial cancer, stomach cancer, and ovary cancer, was observed. Patients with genetic alterations were more closely associated with a family history of cancers, double primary cancers, and the development of secondary neoplasms than patients without genetic alterations (P < 0.0001, P=0.0052, and P=0.0010, respectively). CONCLUSIONS: We report the distribution of pathogenic variants in MLH1, MSH2, and MSH6, as well as the tumor spectrum, in a large sample of Korean patients with LS. Genetic testing could be an effective stratification strategy for surveillance of LS. This study sheds light on the genetic features of Asian patients with LS.
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Feminino , Humanos , Povo Asiático , Neoplasias Colorretais , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias do Endométrio , Testes Genéticos , Coreia (Geográfico) , Instabilidade de Microssatélites , Neoplasias Ovarianas , Neoplasias GástricasRESUMO
Hereditary colorectal cancer can be divded into two categories based on the presence or absence of polyps. The first category is characterized by the development of polyposis, which includes familial adenomatous polyposis (FAP); The second category is nonpolyposis colorectal cancer, which is represented by Lynch syndrome. "Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China" developed by the Genetics Group of the Committee of Colorectal Cancer, Chinese Anti-cancer Association, is composed of three sections, including hereditary nonpolyposis syndrome, polyposis syndrome as well as genetic evaluation of hereditary colorectal cancer. The consensus aims to provide recommendations on management of the respective hereditary syndromes in terms of definition, clinical and pathological features, diagnostic standards, treatment, and follow-ups. In addition to describing diagnostic and treatment strategies, prophylactic treatment as well as genetic screening and pedigree monitoring is highly recommended. Through the establishment of this expert consensus, we hope to promote better understanding of hereditary colorectal cancer for clinicians and encourage standardized treatment through multidisciplinery approaches, eventually improving clinical treatment and pedigree management of hereditary colorectal cancer in China.
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Humanos , Polipose Adenomatosa do Colo , Diagnóstico , Terapêutica , China , Neoplasias Colorretais Hereditárias sem Polipose , Diagnóstico , Terapêutica , Consenso , LinhagemRESUMO
El objetivo de este trabajo fue caracterizar demográfica y molecularmente las familias con diagnóstico de síndrome de Lynch en base a estudios genéticos. Se utilizó la base prospectiva del Registro de Epidemiología Molecular de Cáncer Colorrectal (REM-CCR) del Hospital Italiano de Buenos Aires (Clinical trials.gov NCT02781337). El criterio de inclusión fue que tuvieran hecho un estudio genético entre 1996 y 2017 (secuenciación y/o determinación de grandes rearreglos de al menos un gen reparador de error de apareamiento). Se analizaron 50 familias con los criterios de Amsterdam. En 23 (46%) se identificaron variantes patogénicas (n=19) y probablemente patogénicas (n=2). El 28.6% de las variantes patogénicas fueron originalmente descritas en esta serie, entre ellas la variante c.1911del en el exón 12 de MSH2 identificada en una familia con agregación de cáncer de mama. Fue identificada una mutación fundadora de Piamonte, Italia (c.2252_2253del). Los genes afectados incluyeron MSH2 (13 variantes) MLH1 (9 variantes) y PMS2 (1 variante). La tasa de detección de mutaciones fue del 46%. Entre las familias con mutación identificada (n=23), se detectó una edad mediana de inicio del cáncer menor (46 vs. 50 años, p=0.02) y mayor incidencia de tumores extra-colorrectales (90.5% vs. 45.8%, p <0.01), que las 27 sin mutaciones. La implementación de estudios genéticos permitió caracterizar variables demográficas en base a la identificación de mutaciones germinales asociadas al síndrome de Lynch, identificándose dos grupos diferenciados por la edad de afectación y la incidencia de tumores extracolónicos (AU)
The aim of this study was to characterize demographically and molecularly families diagnosed with Lynch syndrome based on genetic studies. Families with a genetic study performed between 1996 and 2017 (sequencing and/or determination of large rearrangements of a mismatch repair gene at least) were selected from the prospective database REM-CCR of Hospital Italiano de Buenos Aires (Clinical trials. Gov NCT02781337). Fifty families fulfilled Amsterdam criteria were analyzed. Pathogenic variants were found in 23 out of 50 (46%) families, being 21 pathogenic and 2 likely pathogenic. The 28.6% of the pathogenic variants were originally described in this series. Among them, the variant c.1911del in MSH2 in a family with breast cancer aggregation and a founder MLH1 mutation from Piedmont, Italy (c.2252_2253del) were identified. Affected genes include MSH2 (13 variants), MLH1 (9 variants), PMS2 (1 variant). Mutations detection rates was 46%. Those families with an identified mutation (n=23) had a lower median age of cancer onset (46 vs. 50 years, p=0.02) and a higher incidence of extra-colorectal tumors (90.5% vs. 45.8%, p<0.01) than those without identified mutations (n=27). The implementation of genetic studies allowed characterizing demographic variables based on the identification of germline mutations associated with Lynch syndrome. Two groups, Síndrome de Lynch: impacto de la caracterización de familias en base a estudios genéticos 3 differentiated by the age of cancer onset and the incidence of extracolonic tumors were characterized (AU)
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Humanos , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Estudos de Associação Genética , Mutação em Linhagem Germinativa , Estudo ObservacionalRESUMO
Objective To explore the clinical significance of colonoscopy follow-up in Chinese Lynch syndrome mismatch repair (MMR) gene mutation carriers.Methods The results of colonoscopy follow-up was analyzed in 194 MMR gene mutation carriers of 50 Lynch syndrome families.The follow-up period was from April 2001 to November 2016.The detection rates of advanced adenomas and colorectal cancers,five-year survival rate and ten year survival rate were compared between 123 patients of regular follow-up group (colonoscopy interval less than two years) and 71 patients of irregular follow-up group (time colonoscopy interval more than two years).T test,chi-square test and Kaplan-Meier method were performed for statistically analysis.Results The incidence of colorectal cancer of irregular follow up group was significantly higher than that of regular follow-up group (57.7％,41/71 vs 22.8％,28/123);and the difference was statistically significant (x2 =24.00,P＜0.01).The average age at diagnosis for colorectal cancer in irregular follow up group was younger than that of regular follow up group ((45.3 ± 1.9) years vs (48.7±1.8) years);and the difference was statistically significant (t=4.10,P＜0.01).In regular follow-up group,28.6％ (8/28) advanced-stage colorectal cancer (TNM Ⅲ or Ⅳ) was found,while in irregular follow up group,73.2 ％ (30/41) advanced-stage colorectal cancer was found,and there was statistically significant difference in pathological stage between two groups (x2 =4.90,P =0.032).The five year and ten-year survival rates of regular follow-up group were 96.2 ％ and 85.1 ％,respectively,which were both higher than those of irregular follow-up group (46.3 ％ and 28.7 ％);and the differences were statistically significant (x2 =13.20 and 14.80,both P＜0.05).The incidence of advanced adenomas of irregular follow up group was significantly higher than that of regular follow-up group (49.3％,35/71 vs 18.7％,23/123);and the difference was statistically significant (x2 =20.10,P＜0.05).The detection rate of advanced adenomas of MMR gene mutation carriers was higher than those without MMR mutation gene (85.4％,35/41 vs 14.6％,6/41);and the difference was statistically significant (x2 =5.20,P＜ 0.05).Conclusion Regular colonoscopy surveillance may decrease the incidence and mortality of colorectal cancer in MMR mutation carriers of Lynch syndrome families,and increase five-year and tenyear survival rates.
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Objective: To investigate the expression and clinical significance of mismatch repair genes (MMR) MLH1, MSH2, MSH6, and PMS2 in colorectal carcinoma. Methods: Colorectal cancer tissues, collected from 607 patients enrolled in Sichuan Provincial People's Hospital from January 2015 to September 2016, were assigned into two groups based on whether the samples were positive or nega-tive for MMR expression to determine the relationship between MMR expression and clinicopathology. We then evaluated the diag-nostic value of MMR expression in the screening of Lynch syndrome and sporadic colorectal cancer. Results: The deletion rate of MMR protein was 35.58%. No statistically significant difference in age, sex, tumor size, P53, CD34, and D2-40 expression was detected be-tween the negative group with MMR protein deficiency and the positive group with normal expression (P>0.05). Differences in tumor location, differentiation, TNM stage, lymph node metastasis, and VEGF and Ki-67 expression between the two groups were statistically significant (P<0.05). The combined detection of MLH1, MSH2, PSM2, and MSH6 proteins may serve as a simple and economical meth-od for screening patients with Lynch syndrome. Conclusions: The risk of colorectal cancer can be reduced by MMR detection of surgi-cal specimens from colorectal cancer patients, screening of patients with Lynch syndrome and their family members, and assisting with proper management and intervention.
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OBJECTIVE: Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. METHODS: The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM5 were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. RESULTS: Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM5, but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. CONCLUSION: This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients.
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Humanos , Povo Asiático , Neoplasias Colorretais Hereditárias sem Polipose , Diagnóstico , Reparo de Erro de Pareamento de DNA , Testes Genéticos , Mutação em Linhagem Germinativa , Imuno-Histoquímica , Programas de Rastreamento , Anamnese , Metilação , Instabilidade de Microssatélites , Neoplasias Ovarianas , Medição de RiscoRESUMO
Abstract Background Risk assessment for Lynch Syndrome may be a complex and challenging task. Demonstration of germline mutations has the benefits of confirming Lynch Syndrome diagnosis and may also provide screening and surgical orientation for affected members and relief for non-affected relatives. Objective The present paper aimed to critically review the criteria to diagnose Lynch Syndrome, focusing the attention on the new perspective of adopting universal screening for patients diagnosed with colorectal cancer. Methods We performed a literature review about the rationale and preliminary results of universal testing for Lynch Syndrome. Results The use of selective eligibility criteria to determine who should undergo Lynch Syndrome testing may fail in a substantial proportion of cases. Moreover, universal strategy is feasible, cost-effective and more sensitive than previous methods. However, there still exist problems regarding clinical practice implementation and compliance either by medical doctors and patients. Conclusions Standard guidelines for colorectal cancer screening are not ideal to provide early detection of Lynch Syndrome patients. And although universal screening has been associated with an increased identification of Lynch Syndrome patients, a successful implementation of this approach is still limited by the lack of clinical expertise among physicians, and also requires standardization of the existing protocols for routine genetic screening.
Resumo Introdução A avaliação de risco para síndrome de Lynch (SL) pode ser tarefa complexa e desafiadora. A demonstração de mutações na linha germinal resulta em benefícios, como a confirmação do diagnóstico de SL e também pode proporcionar orientações para a triagem e procedimentos cirúrgicos para os membros afetados, além de trazer alívio para os parentes não afetados. Objetivo Este artigo teve por objetivo oferecer uma revisão crítica dos critérios para o diagnóstico de SL, com enfoque na atenção sobre a nova perspectiva de adoção da triagem universal para pacientes diagnosticados com câncer colorretal (CCR). Métodos Procedemos a uma revisão da literatura com ênfase nas justificativas e resultados preliminares de testes universais para SL. Resultados O uso de critérios seletivos de qualificação, com vistas a determinar quem deveria passar por um teste para SL, pode ser malsucedido em substancial percentual de casos. Foi também constatado que a estratégia universal é exequível, com bom custo-benefício e com maior sensibilidade, em comparação com os métodos previamente utilizados. Contudo, ainda existem problemas concernentes à sua implementação na prática clínica e também na cooperação de médicos e de pacientes. Conclusões As orientações padronizadas para a triagem de CCR não são ideais, em termos de se obter a imediata detecção de pacientes com SL. Por outro lado, embora a triagem universal tenha sido associada a um aumento na identificação de pacientes com SL, a bem-sucedida implementação dessa abordagem fica ainda limitada pela pouca experiência clínica entre os médicos e, além disso, também há a necessidade de padronização dos protocolos existentes para a triagem genética de rotina.