Suspected HNPCC and Amsterdam criteria II: evaluation of mutation detection rate, an international collaborative study

Park, Jae Gahb; Vasen, Hans F. A.; Park, Young Jin; Park, Kyu Joo; Peltomäki, Païvi; Leon, Maurizio Ponzo de; Rodrı́guez-Bigas, Miguel A.; Lubiński, Jan; Beck, N. E.; Bisgaard, Marie Luise; Miyaki, Michiko; Wijnen, Juul T.; Baba, Shigeaki; Lindblom, Annika; Madlensky, Lisa; Lynch, Henry T.

doi:10.1007/s003840100348

Cited by 76 publications

(58 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Figure 1 shows the strategy that has been followed for the identification of kindreds with inherited colorectal tumours attributable to germline mutations of the main DNA mismatch repair genes. In registered or referred patients, accurate genealogical trees were traced, and, on this basis, a high-risk group for genetic cancer was defined, including HNPCC (according to the Amsterdam Criteria), suspected HNPCC (Park et al, 2002) and early-onset (before the age of 50 years) colorectal cancer, representing some 10 -15% of all investigated patients with malignancies of the large bowel. As a successive step, microsatellite instability was assessed in this high-risk group; in MSI þ cases, the expression of the protein encoded by the three main mismatch repair genes was evaluated by immunohistochemistry in tumour samples.…”

Section: Discussionmentioning

confidence: 99%

Genetic testing among high-risk individuals in families with hereditary nonpolyposis colorectal cancer

et al. 2004

View full text Add to dashboard Cite

Hereditary nonpolyposis colorectal cancer (HNPCC) is frequently associated with constitutional mutations in a class of genes involved in DNA mismatch repair. We identified 32 kindreds, with germline mutations in one of three genes hMSH2, hMLH1 or hMSH6. In this study, we purposed to evaluate how many high-risk individuals in each family underwent genetic testing: moreover, we assessed how many mutation-positive unaffected individuals accepted colonoscopic surveillance and the main findings of the recommended follow-up. Families were identified through a population-based registry, or referred from other centres. Members of the families were invited for an education session with two members of the staff. When a kindred was consistent with HNPCC, neoplastic tissues were examined for microsatellite instability (MSI) and immunohistochemical expression of MSH2, MLH1 and MSH6 proteins. Moreover, constitutional mutations were searched by SSCP or direct sequencing of the whole genomic region. Of the 164 subjects assessed by genetic testing, 89 were gene carriers (66 affected -that is, with HNPCC-related cancer diagnosis -and 23 unaffected) and 75 tested negative. Among the 23 unaffected gene carriers, 18 (78.3%) underwent colonoscopy and four declined. On a total of 292 first degree at risk of cancer, 194 (66.4%) did not undergo genetic testing. The main reasons for this were: (a) difficulty to reach family members at risk, (b) lack of collaboration, (c) lack of interest in preventive medicine or 'fatalistic' attitude towards cancer occurrence. The number of colorectal lesions detected at endoscopy in gene carriers was significantly (Po0.01) higher than in controls (noncarriers). We conclude that a large fraction of high-risk individuals in mutation-positive HNPCC families does not undergo genetic testing, despite the benefits of molecular screening and endoscopic surveillance. This clearly indicates that there are still barriers to genetic testing in HNPCC, and that we are unable to provide adequate protection against cancer development in these families.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic testing among high-risk individuals in families with hereditary nonpolyposis colorectal cancer

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Patients were classified into clinical HNPCC when they fulfilled the Amsterdam criteria II, 4 or into suspected HNPCC (s-HNPCC) when they fulfilled the revised criteria for s-HNPCC according to their personal and family cancer histories. 8 Clinical data on pathologic result and patient demographics were retrospectively reviewed. Approval for taking personal and family cancer histories, as well as performing MSI analysis, IHC staining and mutational analysis was granted by the Institutional Review Board of the Seoul National University Hospital and the Seoul National University College of Medicine.…”

Section: Patientsmentioning

confidence: 99%

Hereditary nonpolyposis colorectal cancer in endometrial cancer patients

Yoon

Shin

et al. 2007

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Endometrial cancer is the second most common cancer in hereditary nonpolyposis colorectal cancer (HNPCC). It has often been overlooked to explore the possibility of HNPCC in endometrial cancer patients. Our study was to investigate how many HNPCC patients existed among endometrial cancer patients. Among patients who underwent hysterectomy for endometrial cancer at Seoul National University Hospital from 1996 to 2004, 113 patients were included, whose family history and clinical data could be obtained and tumor specimens were available for microsatellite instability (MSI) testing and immunohistochemical (IHC) staining of MLH1, MSH2 and MSH6 proteins. There were 4 (3.5%) clinical HNPCC patients fulfilling the Amsterdam criteria II, and 2 (2/ 4, 50%) of them carried MSH2 germline mutations. There were also 8 (7.1%) suspected HNPCC (s-HNPCC) patients fulfilling the revised criteria for s-HNPCC, and one (1/8, 12.5%) of them revealed MLH1 germline mutation. In 101 patients, who were not clinical HNPCC or s-HNPCC, 11 patients showed both MSI-high and loss of expression of MLH1, MSH2 or MSH6 proteins, and 2 (2/11, 18.2%) of them showed MSH6 germline mutations. In 113 patients with endometrial cancer, we could find 5 (4.4%) HNPCC patients with MMR germline mutation and 2 (1.8%) clinical HNPCC patients without identified MMR gene mutation. Family history was critical in detecting 3 HNPCC patients with MMR germline mutation, and MSI testing with IHC staining for MLH1, MSH2 and MSH6 proteins was needed in the diagnosis of 2 HNPCC patients who were not clinical HNPCC or s-HNPCC, especially for MSH6 germline mutation. ' 2007 Wiley-Liss, Inc.Key words: endometrial cancer; hereditary nonpolyposis colorectal cancer (HNPCC); microsatellite instability (MSI); mismatch repair gene (MMR); MLH1; MSH2; MSH6The incidence of endometrial cancer has been increasing significantly among general population in Korea over the past decades. 1 According to data on cancer incidence between 1999 and 2001 from the Korea Central Cancer Registry, the crude incidence rate per year is 3.11 cases per 100,000 Korean females.2 In a total of 43,627 new cases of female cancer registered by the Korea Central Cancer Registry in 2002, 825 cases were endometrial cancers, accounting for 1.9% of all malignancies in female. 3Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant inherited disease characterized by high incidence of colorectal cancer (CRC), endometrial cancer and/or a variety of other cancers. 4 Defective DNA mismatch repair (MMR) process is caused by germline mutations in the MMR genes, leading to the development of HNPCC. Germline mutations have been identified in five of these genes, MSH2, MLH1, PMS1, PMS2 and MSH6, and mutations in MSH2, MLH1 and MSH6 appear to account for the MMR defects seen in the majority of HNPCC families. 5Endometrial cancer is the second most common cancer found in HNPCC families. 6 The lifetime risk of endometrial cancer for women with HNPCC is reported 40-60%, which is the same or greater than that o...

show abstract

“…In many studies, authors stress that the treatment of choice for patients with HNPCC with colon cancer is subtotal colectomy with ileorectal anastomosis. Patients who do not undergo such a procedure should have a colonoscopy every year because of a 40% probability of developing metasynchronous colorectal lesions in 10 years (21) According to other research, the most frequent extracolonic tumors in families with a history of HNPCC are: endometrium, stomach, small bowel, urinary tract, liver and biliary tract cancers (12,22). In none of the groups was small bowel cancer found (tab.…”

Section: Discussionmentioning

confidence: 99%

“…The cardinal clinical features of HNPCC are an early age of onset (median 45), frequent proximal localization of tumor, synchronous and metasynchronous colonic le- Due to the fact that qualification based on the Amsterdam criteria covers only a small number of patients with HNPCC, many authors propose new criteria that select a new group of patients suspected of HNPCC (S-HNPCC), (tab. 3) (8,10,11,12).…”

mentioning

confidence: 99%

Hereditary Nonpolyposis Colorectal Cancer in Lower Silesia

Stal¹,

Stembalska²,

Śmigiel³

et al. 2007

Polish Journal of Surgery

View full text Add to dashboard Cite

4Ordynator: dr n. med. M. BębenekThe aim of the study was to assess the frequency of hereditary nonpolyposus colorectal cancer in the Lower Silesia area. Material and methods. The study population consists of 318 patients hospitalized between 2001-2002 on 14 surgical wards in the Lower Silesia area. Patients formed four groups: hereditary nonpolyposis colorectal cancer (HNPCC), suspected HNPCC (S-HNPCC), familial colorectal cancer (FCC) and cancer familial aggregation (CFA). The epidemiological data were analyzed (age on onset, gender, localization, extracolonic tumors in family). Results. 3.77% of all patients with colorectal cancer (CRC) were diagnosed with HNPCC and 6.92% with S-HNPCC. The mean age of CRC onset in HNPCC group was 53.07; in the S-HNPCC group, 62.2. Seven male and 5 female patients were diagnosed with HNPCC; for S-HNPCC, 14 males and 8 females were diagnosed. In the HNPCC group, 55.55% of CRC were situated in the right colon and in 44.55%, the left colon. In the S-HNPCC group, 28.57% CRC was in the right colon and in 71.43%, the left colon. In the HNPCC and S-HNPCC groups, there were 4 patients diagnosed with synchronous sigmoid and rectal adenomas. Two of them were diagnosed during intraoperative colonoscopy. One patient was diagnosed with 3 metachronous lesions. In the families of 6 patients with HNPCC extracolonic tumors were identified. Conclusions. 1. Knowledge of HNPCC criteria ensures proper treatment of the patient and their family. 2. During colonoscopy, the whole colon should be inspected. 3. Patients suspected of HNPCC should undergo intraoperative colonoscopy.

show abstract

Suspected HNPCC and Amsterdam criteria II: evaluation of mutation detection rate, an international collaborative study

Cited by 76 publications

References 18 publications

Genetic testing among high-risk individuals in families with hereditary nonpolyposis colorectal cancer

Genetic testing among high-risk individuals in families with hereditary nonpolyposis colorectal cancer

Hereditary nonpolyposis colorectal cancer in endometrial cancer patients

Hereditary Nonpolyposis Colorectal Cancer in Lower Silesia

Contact Info

Product

Resources

About