Published data were identified by searches of MEDLINE and the NHMRC (Australia) Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer (www.health.gov.au/nhmrc/publicat/pdf/cp62.pdf). Reports in English published from 1993 onwards were selected for inclusion in the reference list.
ReviewFamilial colorectal cancer: pathology and molecular characteristics
Section snippets
A working diagnosis
The principles listed above underlie best-practice guidelines for the clinical management of familial colorectal cancer. Diagnosis depends on the careful collection of evidence in the form of family history and tissue manifestations (clinical, morphological, and molecular). Cancer family clinics, informed by registries that serve as repositories of fully verified data, provide the time-tested means of managing familial bowel cancer in a safe and standard way14. Knowledge of the underlying
Familial adenomatous polyposis
The diagnosis of familial adenomatous polyposis (FAP) is generally straightforward. The main feature is the development of hundreds, if not thousands, of adenomas by the mid-teens (Figure 1). Gardner recognised the extracolonic features (Gardner's syndrome), and other manifestations were documented subsequently (Table 3).16 FAP and Gardner's syndrome are synonymous, but polyp numbers and extracolonic presentations are influenced by the location of the germline mutation within the APC gene and
Hereditary non-polyposis colorectal cancer
The term ‘hereditary non-polyposis colorectal cancer’ (HNPCC) was introduced to highlight a form of autosomal dominant bowel cancer distinct from FAP. More by default than design, this rather imprecise term now equates to a specific syndrome, determined by the inheritance of a mutated DNA-mismatch repair gene (Table 2). No individual clinical feature is pathognomonic for the syndrome (unlike the multiple adenomas in FAP), but combinations of features, recognised mainly by Lynch (Table 4),22, 23
MSI-H colorectal cancer – discrimination of familial and non-familial forms
Familial MSI-H cancers arise through the inheritance of a mutated DNA-mismatch repair gene. Non-familial MSI-H cancers arise mainly through the acquired methylation of the promoter region of hMLH1, leading to biallelic silencing.34 Genetic factors could underlie a tendency towards aberrant methylation, and the division into familial versus non-familial MSI-H cancers may not be absolute.
A surprising amount of basic and clinical research into MSI-H cancers has been done without discrimination
Hyperplastic polyposis
Hyperplastic (metaplastic) polyps have traditionally been regarded as small, innocuous lesions presenting mainly in the rectum and distal sigmoid colon. Colorectal cancer occurs in individuals with large or multiple hyperplastic polyps, and cancers are commonly multiple.39 Familial clusterings have been documented.40 Hyperplastic polyps can show clonal genetic alterations, including mutation of K-RAS41 and loss of chromosome 1p.42 A specific molecular pathway to cancer is associated with the
Mixed polyposis
The term mixed polyposis implies the presence of many polyps of different types (adenoma, serrated adenoma, juvenile polyp, hyperplastic polyp) and polyps combining the features of two or more of the classic types. Polyps are not generally present in large numbers (greater than 100), and no individual type dominates. Two hereditary syndromes have emerged from this loosely described entity: hereditary mixed polyposis syndrome12 and hereditary colorectal adenoma and carcinoma syndrome (Table 2).13
Search strategy and selection criteria
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Cited by (42)
Colorectal cancer in the very young: a comparative study of tumor markers, pathology and survival in early onset and adult onset patients
2016, Journal of Pediatric SurgeryCitation Excerpt :A similar trend was found for distal tumors (48% vs 81%, P < 0.0001). Colorectal cancer is among the most common malignancies diagnosed in the adult population, yet much of our knowledge about its biology comes from studying disease diagnosed in the young [23–27,31,45,46]. Perhaps the best example of this is seen in the study of Familial Adenomatous Polyposis (FAP) and HNPCC.
The Many Faces of Colorectal Cancer
2014, Pathobiology of Human Disease: A Dynamic Encyclopedia of Disease MechanismsClinical genetics of hereditary colorectal cancer
2010, Hematology/Oncology Clinics of North AmericaCitation Excerpt :An earlier-onset syndrome, known as constitutional MMR deficiency syndrome, occurs in the presence of homozygous or heterozygous mutations in MMR genes, especially PMS2.16 LS-associated CRC has a higher incidence of several recognizable histopathologic features, such as poorly differentiated mucinous appearance, characteristic lymphocytic infiltrate, histologic heterogeneity, and signet-ring cell features.17 An identifiable molecular feature of LS-associated CRC is microsatellite instability (MSI).
Polyps of the Large Intestine
2009, Surgical Pathology of the GI Tract, Liver, Biliary Tract and PancreasPolyps of the Large Intestine
2008, Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas: Expert Consult - Online and Print