Comprehensive application of various screening strategies of Lynch syndrome / 中华胃肠外科杂志

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.

Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China / 中华肿瘤杂志

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.

Consensus on clinical diagnosis, treatment and pedigree management of hereditary colorectal cancer in China / 中华肿瘤杂志

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.

Progress on the diagnosis, treatment, and family management of Lynch syndrome / 中国肿瘤临床

Lynch syndrome is the most common type of genetically determined colon-cancer predisposition syndrome, accounting for 5%of all colorectal cancer (CRC) cases. This hereditary syndrome is characterized by the germline mutation of human mismatch repair genes and microsatellite instability. Recent studies have shown that Lynch syndrome and sporadic CRC differ in diagnosis and treat-ment;these results are especially relevant for the clinical management of Lynch syndrome. In this review, we reverted to the original characterization of Lynch syndrome, and the developments in its screening and diagnosis were summarized. Furthermore, the manage-ment of families with this disorder was discussed.

hMLH1 promoter methylation and BRAF mutations in high-frequency microsatellite instability colorectal cancers not fulfilling the revised Bethesda guidelines

PURPOSE: Sporadic colorectal cancers with high-frequency microsatellite instability (MSI-H) are related to hypermethylation of mismatch repair (MMR) genes and a higher frequency of BRAF mutations than Lynch syndrome. We estimated the feasibility of hereditary colorectal cancer based on hMLH1 methylation and BRAF mutations. METHODS: Between May 2005 and June 2011, we enrolled all 33 analyzed patients with MSI-H cancer (male:female, 23:10; mean age, 65.5 +/- 9.4 years) from a prospectively maintained database that didn't match Bethesda guidelines and who had results of hMLH1 methylation and BRAF mutations. RESULTS: Among the 33 patients, hMLH1 promoter methylation was observed in 36.4% (n = 12), and was not significantly related with clinicopathologic variables, including MLH1 expression. BRAF mutations were observed in 33.3% of the patients (n = 11). Four of 11 and five of 22 patients with MSI-H colon cancers were BRAF mutation (+)/hMLH1 promoter methylation (-) or BRAF mutation (-)/hMLH1 promoter methylation (+). Of the 33 patients, 21.2% were BRAF mutation (+)/hMLH1 promoter methylation (+), indicating sporadic cancers. Seventeen patients (51.5%) were BRAF mutation (-)/hMLH1 promoter methylation (-), and suggested Lynch syndrome. CONCLUSION: Patients with MSI-H colorectal cancers not fulfilling the Bethesda guidelines possibly have hereditary colorectal cancers. Adding tests of hMLH1 promoter methylation and BRAF mutations can be useful to distinguish them from sporadic colorectal cancers.

Síndrome de Lynch tipo II. Presentación de caso / Syndrome of Lynch type II. Case presentation

Fundamento: el cáncer colorrectal hereditario no ligado a la poliposis asociado a neoplasias extra intestinales se denomina S índrome de Lynch tipo 2 y su diagnóstico constituye un reto para el personal médico. Objetivo: propiciar mediante la presentación de un caso el pensamiento clínico y la actualización científica en esta entidad para efectuar un diagnóstico más oportuno. Presentación de caso: paciente de 49 años, ingresó por una masa palpable en fosa ilíaca izquierda e hipogastrio. Se realizó resección quirúrgica y se diagnosticó un cistadenocarcinoma mucinoso papilar de ovario para lo cual se le prescribió quimioterapia. Dos años más tarde se ingresó por dolor en hemiabdomen inferior, astenia, mareos y palidez cutáneo mucosa. Tras otra intervención quirúrgica se diagnosticó un adenocarcinoma de colon sigmoides. La paciente falleció posteriormente por un cuadro de sangramiento en sábana y fallo multiórganos. Conclusiones: b asado en los criterios de Ámsterdam y Bethesda se realizó el diagnóstico de un S índrome de Lynch tipo 2. P or la frecuencia de la variante hereditaria no polipósica dentro de los cánceres colorrectales se impone una valoración integral del paciente y un juicio clínico coherente para mejorar la certeza diagnóstica en un síndrome que no es infrecuente sino poco diagnosticado.

Background: hereditary colorectal cancer non-related to polyposis associated to extraintestinal neoplasias is called syndrome of Lynch type II and its diagnosis constitutes a challenge for medical staff. Objective: to make possible through a case presentation the clinical thought and the scientific up-dating in this entity to make a more accurate diagnosis. Case presentation: a forty -nine years old patient was admitted for a palpable mass on the left iliac fossa and hypogastrium. A surgical reception was carried out and a papillary mucinous cystadenocarcinoma of ovary was diagnosed for which chemotherapy was prescribed. Two years she was admitted for lower hemoabdomen pain, asthenia, dizziness and cutaneous mucosa paleness. After another surgery a sigmoid colon adenocarcinoma was diagnosed. Later the patient died due to a bleeding and multiorgan failure. Conclusions: based on the criteria of Amsterdam and Bethesda a diagnosis was made of a syndrome of Lynch type II. Due to the frequency of the non-polyposic hereditary variant of the colorectal cancers it is mandatory an integral evaluation of the patient and a coherent clinical judgment in order to improve the diagnostic certainty in a syndrome which is not infrequent but poorly diagnosed.

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.

Hereditary Colorectal Cancer / 대한소화기학회지

Hereditary syndromes cause approximately 5 to 15% of overall colorectal cancer (CRC) cases. Hereditary CRC is conventionally divided into two major categories: hereditary non-polyposis colorectal cancer (HNPCC) and those related to polyposis syndromes including familial adenomatous polyposis (FAP), Peutz-Jegher syndrome (PJS), and juvenile polyposis (JP). The screening for the cancer and methods of treatment applied to patients with hereditary CRC are quite different from those applied to the general population. The genes responsible for these syndromes has recently identified, as a result, genetic testing has become the most important determining factor in clinical decisions. Germ-line mutation of the APC gene induces FAP, an autosomal dominant disorder, characterized by the development of hundreds to thousands of colonic adenomas. CRC appears in almost all affected individuals by the time they are 50 years of age. An affected individual should undergo colectomy by his/her late teens. Furthermore, according to the findings of genetic testing, at-risk family members also need endoscopic surveillance and surgery. Recently, a mutation on the MYH gene is increasingly being investigated in patients with multiple polyps, and autosomal recessive MYH polyposis is considered to be a new category of polyposis. More common than FAP, HNPCC is caused by germ-line mutations in DNA mismatch repair genes, mainly MLH1 and MSH2. Although there is no polyposis, polyps seem to be more villous and dysplastic and appear to grow rapidly into CRCs. The aggregate lifetime risk of CRC is about 80% for mutation carriers. The risk for other types of cancer, such as endometrial, ovarian, small bowel, and transitional cell cancer, is also increased. The Amsterdam criteria and Bethesda guidelines are the best-known tools for diagnosis and genetic testing, and colectomy followed by endoscopic follow-up is the standard treatment. PJS and JP are reported to be characterized by hamartomatous polyps throughout the GI tract and germ-line mutations in the STK11 gene (PJS) and the DPC4/BMPR1A gene (JP).