Rectal Cancer Risk in Hereditary Nonpolyposis Colorectal Cancer After Abdominal Colectomy

Rodrı́guez-Bigas, Miguel A.; Vasen, Hans F. A.; Pekka-Mecklin, Jukka; Myrhøj, T; Rozen, Paul; Bertario, Lucio; Järvinen, H; Jass, Jeremy R.; Kunitomo, Kazufumi; Nomizu, Tadashi; Driscoll, Deborah L.

doi:10.1097/00000658-199702000-00008

Cited by 150 publications

(57 citation statements)

References 15 publications

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“…32 Emerging issues such as segmental versus total colectomy as primary surgery for HNPCC patients with cancer require timely prediction of the molecular subtype for patient management. 33 In addition, patients with inherited or sporadic MSI-H colon cancers have inherently better stage-specific survival after surgical and adjuvant therapies. 2,7,18,34 -43 Molecular analysis of tumors for MSI is currently timeconsuming and expensive to perform, presenting obstacles to thorough molecular study of all colon cancers before decisions about therapy.…”

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confidence: 99%

Histopathological Identification of Colon Cancer with Microsatellite Instability

Alexander

Watanabe

et al. 2001

The American Journal of Pathology

447

317

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and the Eastern Cooperative Oncology Group, ‡ Brookline, MassachusettesCancer with high levels of microsatellite instability (MSI-H) is the hallmark of hereditary nonpolyposis colorectal cancer syndrome, and MSI-H occurs in ϳ15% of sporadic colorectal carcinomas that have improved prognosis. We examined the utility of histopathology for the identification of MSI-H cancers by evaluating the features of 323 sporadic carcinomas using specified criteria and comparing the results to MSI-H status. Coded hematoxylin and eosin sections were evaluated for tumor features (signet ring cells; mucinous histology; cribriforming, poor differentiation, and medullary-type pattern; sponge-like mucinous growth; pushing invasive margin) and features of host immune response (Crohn's-like lymphoid reaction, intratumoral lymphocytic infiltrate, and intraepithelial T cells by immunohistochemistry for CD3 with morphometry). Interobserver variation among five pathologists was determined. Subjective interpretation of histopathology as an indication for MSI testing was recorded. We found that medullary carcinoma, intraepithelial lymphocytosis, and poor differentiation were the best discriminators between MSI-H and microsatellite-stable cancers (odds ratio: 37.8, 9.8, and 4.0, respectively; P ‫؍‬ 0.000003 to <0.000001) with high specificity (99 to 87%). The sensitivities, however, were very low (14 to 38%), and interobserver agreement was good only for evaluation of poor differentiation (kappa, 0.69). Mucinous histopathological type and presence of signet ring cells had low odds ratios of 3.3 and 2.7 (P ‫؍‬ 0.005 and P ‫؍‬ 0.02) with specificities of 95% but sensitivities of only 15 and 13%. Subjective interpretation of the overall histopathology as suggesting MSI-H performed better than any individual feature; the odds ratio was 7.5 (P < 0.000001) with sensitivity of 49%, specificity of 89%, and moderate interobserver agreement (kappa, 0.52). Forty intraepithelial CD3-positive lymphocytes/0.94 mm 2 , as established by receiver operating characteristic curve analysis, resulted in an odds ratio of 6.0 (P < 0.000001) with sensitivity of 75% and specificity of 67%. Our findings indicate that histopathological evaluation can be used to prioritize sporadic colon cancers for MSI studies, but morphological prediction of MSI-H has low sensitivity, requiring molecular analysis for therapeutic decisions.

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confidence: 99%

Histopathological Identification of Colon Cancer with Microsatellite Instability

Alexander

Watanabe

et al. 2001

The American Journal of Pathology

447

317

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“…use of prophylactic surgery is controversial. 20 Women with MuirTorre syndrome are also at higher risk of endometrial and ovarian cancer. In women of childbearing age, total hysterectomy with salpingo-oophorectomy has been discussed as a prophylactic approach, but there is no consensus on this topic.…”

Section: Discussionmentioning

confidence: 99%

Muir-Torre Syndrome: case report and molecular characterization

et al. 2014

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CONTEXT: Muir-Torre syndrome is a rare autosomal dominant genodermatosis caused by mutations in the mismatch repair genes. It is characterized by the presence of sebaceous skin tumors and internal malignancies, affecting mainly the colon, rectum and urogenital tract. Awareness of this syndrome among physicians can lead to early diagnosis of these malignancies and a better prognosis. CASE REPORT: We report the case of a Chilean patient who, over the course of several years, had multiple skin lesions, endometrial cancer and colon cancer. The syndrome was diagnosed using molecular techniques such as microsatellite instability analysis, immunohistochemistry and DNA sequencing, which allowed us to find the causative mutation. CONCLUSION: Molecular diagnostics is a highly useful tool, since it allows clinicians to confirm the presence of mutations causing Muir-Torre syndrome. It is complementary to the analysis of the clinical data, such as dermatological presentation, presence of visceral malignancies and family history of colorectal tumors, and it provides important knowledge to help physicians and patients choose between treatment options.RESUMO CONTEXTO: A síndrome de Muir-Torre é uma genodermatose autossômica dominante rara causada por mutações nos genes de reparo de incorreções. Caracteriza-se pela presença de tumores sebáceos da pele e doenças malignas internas, afetando principalmente cólon, reto e trato urogenital. A consciência desta síndrome pelos médicos pode levar ao diagnóstico precoce dessas doenças malignas e a um melhor prognóstico. RELATO DE CASO: Relatamos o caso de uma paciente chilena que, ao longo de vários anos, teve lesões cutâneas múltiplas, câncer de endométrio e câncer de cólon. A síndrome foi diagnosticada com técnicas moleculares, como a análise de instabilidade de microssatélites, imunoistoquímica e sequenciamento de DNA, o que nos permitiu encontrar a mutação causadora. CONCLUSÃO: Diagnóstico molecular é uma ferramenta muito útil, uma vez que permite que os clí-nicos confirmem a presença de mutações causadoras de síndrome de Muir-Torre. É complementar para a análise dos dados clínicos, tais como a apresentação dermatológica, a presença de doenças malignas viscerais e história familiar de tumores colorrectais, e fornece conhecimentos importantes para ajudar os médicos e os pacientes a escolher entre opções de tratamento.

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“…The risk of rectal cancer in Lynch syndrome patients after subtotal colectomy is estimated at 12% at 12 years, so annual surveillance of the rectum should be performed (46).…”

Section: Surgical Treatment In Hereditary Colon Cancer Syndromesmentioning

confidence: 99%

Recognition and management of hereditary colorectal cancer syndromes

Herraiz

Muñoz-Navas

2009

Rev. esp. enferm. dig.

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Over 1.900 colorectal tumors will arise in association with a hereditary colorectal cancer syndrome in Spain in 2009.The genetic defects responsible for the most common syndromes have been discovered in recent years.Genetic testing helps diagnose affected individuals and allows identification of individuals at-risk.Colonoscopy and prophylactic colectomy decrease colorectal cancer incidence and overall mortality in patients with hereditary colon cancer.Extracolonic tumors are frequent in these syndromes, so specific surveillance strategies should be offered.Key words: Familial adenomatous polyposis. Lynch syndrome. MYH-associated polyposis. Hereditary colon cancer. INTRODUCTIONIn 2009, it is estimated that around 38,000 people (1) in Spain will be diagnosed with colorectal cancer (CRC). Among these cases, more than 15% will exhibit familial clustering, and over 1,900 tumors (5%) will arise in association with a hereditary colorectal cancer syndrome. The most common hereditary colon cancer syndromes are: Familial Adenomatous Polyposis (FAP), attenuated FAP (AFAP), MYH associated polyposis (MAP), and Lynch syndrome, also known as Hereditary Non-Polyposis Colorectal Cancer syndrome (HNPCC) (2).During the last two decades, the most important advancement has been the identification of the genes that underlie these syndromes. This has permitted more accurate classifications of the various syndromes based upon genetic criteria, and consequently this has resulted in more tailored management strategies based on these criteria (3). The management of individuals with hereditary colon cancer or at-risk for hereditary colon cancer is dramatically different, so recognizing these syndromes is critical. Specifically, surveillance strategies for colon and extra-colonic tumors as well as surgical approaches (4) for the prevention and treatment of cancer reflect the heightened risks.This review is focused on current treatment strategies in hereditary colon cancer. It is important to recognize that "treatment" includes not only management of already diagnosed cancers but also to prevention of cancer in these high-risk populations. We first briefly summarize the major clinical features of each syndrome, including pattern of inheritance and penetrance, age at diagnosis and associated extra-colonic tumors. Familial adenomatous polyposis and attenuated FAPFAP is the most common adenomatous polyposis syndrome. Its prevalence is 1:5.000-10.000, with a uniform worldwide distribution, affecting both genders equally (5). Inherited in an autosomal dominant manner with a virtually penetrance of 100%, it is caused by a germline mutation in the Adenomatous Polyposis Coli (APC) tu- POINT OF VIEWmor suppressor gene on chromosome 5q21 (6). In 15-20%, the cases are "de novo" without clinical or genetic evidence of FAP in the parents (7). Recent studies indicate the presence of mosaicism in approximately 15% of such cases (8,9).Classic FAP is characterized by the development of hundreds to thousands of colorectal adenomas starting during the...

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Rectal Cancer Risk in Hereditary Nonpolyposis Colorectal Cancer After Abdominal Colectomy

Cited by 150 publications

References 15 publications

Histopathological Identification of Colon Cancer with Microsatellite Instability

Histopathological Identification of Colon Cancer with Microsatellite Instability

Muir-Torre Syndrome: case report and molecular characterization

Recognition and management of hereditary colorectal cancer syndromes

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