Constitutional mismatch repair deficiency syndrome: Do we know it.

Constitutional mismatch repair deficiency syndrome is a rare autosomal recessive syndrome caused by homozygous mutations in mismatch repair genes. This is characterized by the childhood onset of brain tumors, colorectal cancers, cutaneous manifestations of neurofibromatosis‑1 like café au lait spots, hematological malignancies, and occasionally other rare malignancies. Here, we would like to present a family in which the sibling had glioblastoma, and the present case had acute lymphoblastic lymphoma and colorectal cancer. We would like to present this case because of its rarity and would add to literature.

Expression of hMLH1 and hMSH2 in suspected hereditary non-polyposis colorectal cancer / 实用医学杂志

Objective To analyse the suspected hereditary non-polyposis colorectal cancer (HNPCC) in mismatch repair protein (MMR) expression of hMLH1 and hMSH2. Methods Immunohistochemical staining method was used for the detection of hMLH1 and hMSH2 protein expression in 193 cases suspected HNPCC patients, the deletion of MMR proteins was identified as highly suspected HNPCC cases. Results Of the 193 patients with suspected HNPCC hMLH1/hMSH2 abnormal expression rate was 29.02%; ≤30 years old was 40%, 31 ~ 40 years old was 28.05%, 41 ~ 50 years old was 28.71%,3 suspected HNPCC showed the deletion of hMLH1/hMSH2 protein expression at the same time ,; In the right colon , the left half colon and rectal anomaly detection rates were 40.74%, 32.65%and 18.89%; hMLH1/hMSH2 deletion was 46.15%with family history. Conclusions The deletion of MMR protein is closely related to age,site and family history in suspected HNPCC, and the deletion of hMLH1 is an important factor to induce early-set colorectal cancer. The deletion of hMLH1/hMSH2 at the same time indicates that hMLH1/hMSH2 genes may play important role in the incidence of HNPCC.

Historical review of Lynch syndrome / Revisão histórica da síndrome de Lynch

Lynch syndrome was formerly known as Hereditary Nonpolyposis Colorectal Cancer. Currently, these two nomenclatures each have their unique definitions and are no longer used interchangeably. The history of hereditary nonpolyposis colorectal cancer was first recognized formally in the literature by Henry Lynch in 1967. With advances of molecular genetics, there has been a transformation from clinical phenotype to genotype diagnostics. This has led to the ability to diagnose affected patients before they manifest with cancer, and therefore allow preventative surveillance strategies. Genotype diagnostics has shown a difference in penetrance of different cancer risks dependent on the gene containing the mutation. Surgery is recommended as prevention for some cancers; for others they are reserved for once cancer is noted. Various surveillance strategies are recommended dependent on the relative risk of cancer and the ability to intervene with surgery to impact on survival. Risk reduction through aspirin has shown some recent promise, and continues to be studied. (AU)

A síndrome de Lynch era anteriormente conhecida como "câncer colorretal hereditário não polipose". Atualmente, essas duas nomenclaturas têm, cada uma, sua própria definição original e já não são empregadas de forma intercambiável. O histórico de câncer colorretal hereditário não polipose foi formalmente reconhecido pela primeira vez na literatura por Henry Lynch em 1967. Com os avanços da genética molecular, verificou-se uma mudança do fenótipo clínico para o diagnóstico genotípico. Esse fato levou à capacidade de diagnosticar pacientes afetados antes que o câncer se manifestasse, e, portanto, à utilização de estratégias preventivas de rastreamento. O diagnóstico genotípico mostrou a diferença na penetrância de diferentes riscos de câncer dependendo do gene que contem a mutação. A cirurgia é recomendada para a prevenção de alguns tipos de câncer; para outros, ela é reservada quando há o aparecimento da doença. Várias estratégias de rastreamento são recomendadas, dependendo do risco relativo de câncer, bem como a capacidade para intervir com a cirurgia objetivando um impacto na sobrevivência. A redução do risco através do uso de aspirina recentemente mostrou ser promissor e continua a ser estudada. (AU)

Knowledge of and Practice Patterns for Hereditary Colorectal Cancer Syndromes in Korean Surgical Residents

PURPOSE: Obtaining a detailed family history through detailed pedigree is essential in recognizing hereditary colorectal cancer (CRC) syndromes. This study was performed to assess the current knowledge and practice patterns of surgery residents regarding familial risk of CRC. METHODS: A questionnaire survey was performed to evaluate the knowledge and the level of recognition for analyses of family histories and hereditary CRC syndromes in 62 residents of the Department of Surgery, Seoul National University Hospital. The questionnaire consisted of 22 questions regarding practice patterns for, knowledge of, and resident education about hereditary CRC syndromes. RESULTS: Two-thirds of the residents answered that family history should be investigated at the first interview, but only 37% of them actually obtained pedigree detailed family history at the very beginning in actual clinical practice. Three-quarters of the residents answered that the quality of family history they obtained was poor. Most of them could diagnose hereditary nonpolyposis colorectal cancer and recommend an appropriate colonoscopy surveillance schedule; however, only 19% knew that cancer surveillance guidelines differed according to the family history. Most of our residents lacked knowledge of cancer genetics, such as causative genes, and diagnostic methods, including microsatellite instability test, and indicated a desire and need for more education regarding hereditary cancer and genetic testing during residency. CONCLUSION: This study demonstrated that surgical residents' knowledge of hereditary cancer was not sufficient and that the quality of the family histories obtained in current practice has to be improved. More information regarding hereditary cancer should be considered in education programs for surgery residents.

Knowledge of and Practice Patterns for Hereditary Colorectal Cancer Syndromes in Korean Surgical Residents

PURPOSE: Obtaining a detailed family history through detailed pedigree is essential in recognizing hereditary colorectal cancer (CRC) syndromes. This study was performed to assess the current knowledge and practice patterns of surgery residents regarding familial risk of CRC. METHODS: A questionnaire survey was performed to evaluate the knowledge and the level of recognition for analyses of family histories and hereditary CRC syndromes in 62 residents of the Department of Surgery, Seoul National University Hospital. The questionnaire consisted of 22 questions regarding practice patterns for, knowledge of, and resident education about hereditary CRC syndromes. RESULTS: Two-thirds of the residents answered that family history should be investigated at the first interview, but only 37% of them actually obtained pedigree detailed family history at the very beginning in actual clinical practice. Three-quarters of the residents answered that the quality of family history they obtained was poor. Most of them could diagnose hereditary nonpolyposis colorectal cancer and recommend an appropriate colonoscopy surveillance schedule; however, only 19% knew that cancer surveillance guidelines differed according to the family history. Most of our residents lacked knowledge of cancer genetics, such as causative genes, and diagnostic methods, including microsatellite instability test, and indicated a desire and need for more education regarding hereditary cancer and genetic testing during residency. CONCLUSION: This study demonstrated that surgical residents' knowledge of hereditary cancer was not sufficient and that the quality of the family histories obtained in current practice has to be improved. More information regarding hereditary cancer should be considered in education programs for surgery residents.

Korean Nurses' Knowledge about Hereditary Colorectal Cancer / 종양간호학회지

PURPOSE: This study was performed to evaluate Korean nurses' knowledge about hereditary colorectal cancer (HCRC). METHODS: A modified 15-item HCRC knowledge questionnaire was developed based on previous research. One hundred and forty-eight nurses have completed the questionnaire from February to April, 2011. RESULTS: The average score of nurses' knowledge was 11.25+/-1.54. Ninety-seven percent of nurses knew about colonoscopy check up schedule and family pedigree. However, only 20% of nurses knew about the rate of passing on mutation genes to offspring and risk of developing CRC among carriers. Only 13.5% of nurses had previous genetic education experiences. Working in oncology units, taking care of CRC patients, and participating in genetic education were not associated with nurses' HCRC knowledge. CONCLUSION: Various factors influence nurses' knowledge about HCRC. Repeated study with larger national sample of nurses is recommended to identify the factors affecting nurses' knowledge level in order to develop efficient genetic education programs for HCRC patients and their families by nurses.

Jejunal Adenocarcinoma as Part of Metachronous Triple Primary Cancers of the Digestive Tract in Patient with Hereditary Nonpolyposis Colorectal Cancer

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant inherited disease characterized by onset at a relatively early age, an excess of synchronous and metachronous tumors, and a variety of extracolorectal malignancies. Small bowel carcinoma reported, is included in the tumor spectrum of HNPCC, but the frequency of occurrence of this tumor in HNPCC patients is comparatively rare. In Korea, several cases of multiple primary cancers in patients with HNPCC have been reported, however, primary jejunal adenocarcinoma in conjunction with multiple primary cancers in the digestive tract has rarely been reported. Recently, we evaluated a 61-year-old male diagnosed with metachronous triple primary cancers of the jejunum, stomach, and colon. We report this rare case of primary jejunal adenocarcinoma as a part of metachronous triple cancers along with a review of the relevant literature.

Identification of nonfamilial MSI-H colorectal cancer based on clinicopathological features / 基础医学与临床

Objective To identify clinicopathological features of high MSI (MSI-H).Methods We enrolled 150 patients,standard microsatellite loci (BA T25,BA T26,D2S123,D5S346,D17S250) were amplified by polymerase chain reaction(PCR) with fluorescent primers,and the PCR products were analyzed by GeneMapper software;age at diagnosis,gender and site were obtained;various pathological features were observed by light microscopy;the expression of tumor infiltrating lymphocytes (CD4~+ and CD8~+) was detected by immunohistochemistry.Using a stepwise logistic regression model,a formula was generated that could be used to calculate the probability of a colorectal carcinoma being MSI-H based on pathological features.Results Among 150 cancers,MSI-H was 13.33%.Independent identifiers inclucle poor differentiation,histologic heterogeneity,Crohn's-like reaction and tumor-infiltrating lymphocytes,logistic regression formula shows a sensitivity of 70.0% and a specificity of 99.2% and a accurate ratio of 95.3% for MSI-H.Conclusion MSI-H phenotype cancer is a type of nonfamilial colorectal cancer with specific pathological features,Clinicopathological features can efficiently identify MSI-H colorectal cancers.

Hereditary Colorectal Cancer

Colorectal cancer is one of the most steeply increasing malignancies in Korea. Among 398,824 new patients recorded by the Korea Central Cancer Registry between 2003 and 2005, 47,915 cases involved colorectal cancers, accounting for 12.0% of all malignancies. In 2002, total number of colorectal cancer cases had accounted for 11.2% of all malignancies. Hereditary syndromes are the source of approximately 5% to 15% of overall colorectal cancer cases. Hereditary colorectal cancers are divided into two types: hereditary nonpolyposis colorectal cancer (HNPCC), and cancers associated with hereditary colorectal polyposis, including familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, juvenile polyposis, and the recently reported hMutYH (MYH)-associated polyposis (MAP). Hereditary colorectal cancers have unique clinical features distinct from sporadic cancer because these are due to germline mutations of the causative genes; (i) early age-of-onset of cancer, (ii) frequent association with synchronous or metachronous tumors, (iii) frequent association with extracolonic manifestations. The management strategy for patients with hereditary colorectal cancer is quite different from that for sporadic cancer. Furthermore, screening, genetic counseling, and surveillance for at-risk familial member are also important. A well-organized registry can plays a central role in the surveillance and management of families affected by hereditary colorectal cancers. Here, we discuss each type of hereditary colorectal cancer, focusing on the clinical and genetic characteristics, management, genetic screening, and surveillance.

Mismatch repair genes in Lynch syndrome: a review: [review] / Genes de reparo de DNA na síndrome de Lynch: uma revisão: [revisão]

Lynch syndrome represents 1-7 percent of all cases of colorectal cancer and is an autosomal-dominant inherited cancer predisposition syndrome caused by germline mutations in deoxyribonucleic acid (DNA) mismatch repair genes. Since the discovery of the major human genes with DNA mismatch repair function, mutations in five of them have been correlated with susceptibility to Lynch syndrome: mutS homolog 2 (MSH2); mutL homolog 1 (MLH1); mutS homolog 6 (MSH6); postmeiotic segregation increased 2 (PMS2); and postmeiotic segregation increased 1 (PMS1). It has been proposed that one additional mismatch repair gene, mutL homolog 3 (MLH3), also plays a role in Lynch syndrome predisposition, but the clinical significance of mutations in this gene is less clear. According to the InSiGHT database (International Society for Gastrointestinal Hereditary Tumors), approximately 500 different LS-associated mismatch repair gene mutations are known, primarily involving MLH1 (50 percent) and MSH2 (40 percent), while others account for 10 percent. Much progress has been made in understanding the molecular basis of Lynch Syndrome. Molecular characterization will be the most accurate way of defining Lynch syndrome and will provide predictive information of greater accuracy regarding the risks of colon and extracolonic cancer and enable optimal cancer surveillance regimens.

A síndrome de Lynch representa de 1-7 por cento de todos os casos de câncer colorretal. É uma síndrome de herança autossômica dominante que predispõe ao câncer e é causada por mutações nos genes de reparo de ácido desoxirribonucléico (DNA). Desde a descoberta dos principais genes com função de reparo de DNA, mutações nos genes MSH2, MLH1, MSH6, PMS2 e PMS1 estão relacionadas com a susceptibilidade à síndrome de Lynch. Outro gene, MLH3, tem sido proposto como tendo papel na predisposição à síndrome de Lynch, porém mutações de significância clínica nesse gene não são claras. De acordo com o banco de dados InSiGHT (International Society for Gastrointestinal Hereditary Tumors), aproximadamente 500 diferentes mutações associadas à síndrome de Lynch são conhecidas, envolvendo primeiramente MLH1 (50 por cento), MSH2 (40 por cento) e outros (10 por cento). Grandes progressos têm ocorrido para nosso entendimento das bases moleculares da síndrome de Lynch. A caracterização molecular será a forma mais precisa para definirmos a síndrome de Lynch e irá fornecer informações preditivas mais precisas sobre o risco de câncer colorretal e extra-colônico, além de permitir regimes otimizados de manejo.

Clinical characteristic,diagnosis and therapy of hereditary nonpolyposis colorectal cancer in 32 cases of 11 families / 中国癌症杂志

Purpose:To study the clinic characteristic, diagnosis and therapy of hereditary nonpolypoid colorectal cancer.Methods:We analysed the diagnosis, therapy and follow up of hereditary nonpolypoid colorectal cancer in 32 cases from 11 families by studying the tumour site, pathologic results. Results:There were 43 cancer patients having 61 tumours in 11 families, and 32 cases were intestinal cancer with 39 tumours. In these 32 cases, there were 12 hereditary nonpolypoid colorectal cancer (37.5), and 5 cases were intestinal cancer (15.6). We examined the patients and their direct relatives and found 28 people had various cancer, of which 20 cases without any complaint. Conclusions:Hereditary nonpolypoid colorectal cancer is a dominant hereditary disease, with the characteristic of early flare up,prone to upper colon. They are always non contemporary polygeneous cancer or contemporary polygeneous cancer, and prone to take place outside of colon. So it is important not only for patients to be treated and followed up but also for their relatives to be instructed and followed up. We must study the disease history in details. [

Clinicopathological study of hereditary nonpolyposis colorectal cancer families in China / 中华消化杂志

Objective To study the clinicopathological characteristics of hereditary nonpolyposis colorectal cancer (HNPCC) in Chinese population with different criteria and guidelines. Methods Twenty four families fulfilling Amsterdam Criteria (AC), 15 additional families fulfilling Japanese Criteria (JC) and the remaining 19 patients fitting Bethesda Guidelines (BG) were analyzed. Results In the 24 AC families there were 116 malignant tumor patients including 90 colorectal cancer (CRC) subjects and in the 15 JC families there were 54 malignant tumor patients including 33 CRC cases. The two groups displayed similar clinical features. Mean age of first CRC at diagnosis was 46.1 and 51.4 years old, respectively. The proximal colonic cancers accounted for 55.4% versus 44.8%. Synchronous and metachronous multiple CRCs occurred in 25.6% and 18.2% of patients respectively. Totally there were 55 extracolonic tumors in the two groups. Gastric and endometrial carcinomas were two most common extracolonic tumor types in our series. The tumors of the 34 probands showed more frequent exophytic growth pattern, higher occurance of poorly differentiated carcinoma, A / B Dukes stage and more Crohn's like lymphoid reaction ( P

Analysis the features of extracolonic cancer in hereditary nonpolyposis colorectal cancer spectam / 临床外科杂志

Objective Analysis the features of extracolonic cancer of HNPCC.Method 32 families with HNPCC were registered and followed up.Results Among 12 families with typical HNPCC,8 cases in 6 families and 1 case of nontypical HNPCC families developed extracolonic cancer. Endometrial and gastric cancers are the most common cancers.Conclusions The extracolonic cancers are the important part in the cancer spectum of HNPCC. Among Chinese families, endometrial and gastric cancers are more common.

Clinical Characteristics of Korean Hereditary Nonpolyposis Colorectal Cancer

Hereditary nonpolyposis colon cancer(HNPCC) accounts for 1~6% of colorectal cancer. Mutations in the DNA mismatch repair genes(hMSH2, hMLH1 and hPMS1, hPMS2 and hMSH6) are responsible for HNPCC. To evaluate the clinical characteristics of Korean HNPCC patients, analysis were performed on the 176 patients from 40 HNPCC families registered in the Korean Hereditary Tumor Registry. All the families in this study fulfilled the ICG-HNPCC criteria. The control group consisted of 1,204 patients of nonhereditary colorectal cancer operated at SNUH between 1991 and 1995. The mean age of patients at diagnosis was significantly lower than the control group (44.5 vs 56.1 years old). Thirty three percent of cancers were located proximal to splenic flexure compared to 23% in control group. Among the 71 patients whose pathological reports were available, 14 patients(20%) had synchronous colorectal cancer compared to 4% in control. Also 15 patients(21%) had synchronous adenomatous polyp and 3 patients had both the synchronous cancer and polyp. Thus, overall 26 patients (36%) had multiple colorectal cancer including polyp. The cancers in HNPCC patients were detected at significantly earlier stage than control(67% of HNPCC patients were Dukes A or B compared to 48% in control). Statis tically significant difference was not observed in tumor differentiation between HNPCC and control group. In terms of treatment, 64% of patients received an extensive surgery over subtotal colectomy between 1995~1997 compared to 31% in the period of 1991~1994. In this series, we confirmed that Korean HNPCC patients have similar characteristics with western countries in that an early age of onset, a proclivity for the proximal colon and excess of synchronous colorectal cancers. However, relatively low incidence of proximal colonic involvement and low rate of mucinous or poorly differentiated carcinoma differed from the reports from the western countries.

Clinical Characteristics of Colorectal Cancer and Prognosis for Patients Younger Than 40 Years Old

BACKGROUND: Although the incidence of colorectal cancer in young adults is low, they seem to show advanced tumors with a poor prognosis at their initial presentation due to diagnostic delay. We evaluated colorectal cancer in young patients with respect to clinical characteristics and prognosis. METHODS: Twelve hundred and seventy-three colorectal cancer patients were evaluated retrospectively. Familial adenomatous polyposis and ulcerative colitis related cases were excluded. We grouped these patients into younger (40 years old) and older (>40 years old) patients. These two groups were compared with respect to sex, tumor location, duration of symptoms and signs, patterns of DNA ploidy, histological differentiations, TNM stage, survival rate, and familial tendency of colorectal cancer. RESULTS: One hundred forty-nine patients (11.7%) were 40 years old or younger. There was no significant difference between the two groups with respect to sex, tumor location, patterns of DNA ploidy, and 5-year survival rate. Histological patterns revealed a higher incidence of mucinous and signet-ring cell tumors in the younger group than in the older group (12.7% vs. 2.7% and 4.0% vs. 0.7%, p<0.05). The duration of the symptoms was shorter in the younger group, being less than 3 months in 56.3% of the younger group and 36.3% of the older group. Colorectal cancer in the younger group seemed to present more advanced lesions, especially those in stage III. Familial clustering of cancers(younger group, 25.5%; older group, 9.3%) and hereditary nonpolyposis colorectal cancer(younger group, 7.4%; older group, 0.7%) were more prevalent in the younger group. CONCLUSION:For colorectal cancer in younger patients with histological shortcomings and familial clustering, every effort is needed to make an earlier diagnosis.