Do all colorectal carcinomas arise in preexisting adenomas?

In this article, the underlying nature of the adenoma is defined and evidence in support of the adenoma-carcinoma sequence is presented. Emphasis is placed on recent findings from the field of molecular biology which fortify the concept of the adenoma as a step in the evolution of large bowel cancer. Despite the considerable body of indirect evidence in support of the adenoma-carcinoma sequence, the de novo theory still has some support. Although differences between the de novo and adenoma-carcinoma concept are largely semantic, the fact that infiltrating carcinoma can arise within small, flat foci of severely dysplastic epithelium (indistinguishable from carcinoma in situ) may be of considerable clinical importance. Other routes of morphogenesis exist also, but these make a relatively small contribution to the overall incidence of colorectal cancer. Even if it is accepted that the majority of colorectal cancers develop in a preexisting adenoma, the systematic removal of adenomas would pose a number of practical difficulties. First, adenomas are extremely common, particularly in populations at high risk of colorectal cancer. A second factor is the recently recognized existence of flat or depressed adenomas which may be small and difficult to visualize endoscopically. A simple screening program based on our knowledge of the evolution of colorectal cancer is outlined.RésuméLa nature et le potentiel de croissance des adénomes et notablement l'évidence en faveur de la séquence adénome-cancer sont présentés. En particulier, des données récentes en biologie moléculaire semblent renforcer la conception de la progression adénome-cancer du côlon. Malgré ce, l'hypothèse du développement de novo des cancers intestinaux garde ses partisans. En fait les différences entre les deux théories semblent être essentiellement sémantiques: un cancer infiltrant peut se développer à partir de petits foyers aplatis au sein d'un épithélium dysplasique (ce qui ne peut être distingué d'un cancer in situ) et ce fait peut avoir une importance clinique. D'autres modes de morphogenèse sont possibles, mais ne seraient responsables que d'une petite proportion de cancers colorectaux. Même si on accepte le principe que la majorité des cancers se développent à partir des adénomes pré-existants, l'ablation systématique de tous les adénomes pose un certain nombre de problèmes difficiles. Tout d'abord, l'adénome est d'une extrême fréquence, particulièrement dans les populations à haut risque de cancer colorectal. Deuxièmement, il y a la notion d'acquisition plus récente de l'existence d'adénomes plats ou mêmes déprimés et de petite taille et de ce fait de reconnaissance endoscopiquement difficile. Un programme simple de dépistage, basé sur nos connaissances actuelles sur l'évolution du cancer colorectal est schématisé.ResumenEn este artículo se define la naturaleza del adenoma colorrectal y se resume la evidencia sobre la secuencia tejido normaladenoma-carcinoma. Se hace énfasis sobre los hallazgos recientes en el campo de la biología molecular que fortalecen el concepto del adenoma como una fase en la evolución del cáncer del intestino grueso. A pesar de un cuerpo considerable de evidencia en soporte de la secuencia adenoma-carcinoma, la teoría del carcinoma de novo todavía posée apoyo. Aunque las diferencias entre el concepto del carcinoma de novo y el concepto de la secuencia adenoma-carcinoma son principalmente semánticas, el hecho de que un carcinoma infiltrante pueda originarse en focos pequeños y planos de epitelio severamente displásicos (indistinguible del carcinoma in situ), puede ser de importancia clínica considerable. También pueden existir otras rutas de morfogénesis, pero éstas representan una contribución relativamente pequeña a la incidencia global del cáncer colorrectal. Aún si se acepta que la mayoría de los cánceres colorrectales se desarrollan en adenomas preexistentes, la remoción sistemática de los adenomas presentaría un número de dificultades prácticas. En primer lugar, los adenomas son extremadamente comunes, particularmente en poblaciones con alto riesgo de cáncer colorrectal. Un segundo factor es la recientemente reconocida existencia de adenomas planos o deprimidos, los cuales pueden ser muy pequeños y difíciles de visualizar a la endoscopia. Se delinea un sencillo programa de tamizaje fundamentado en nuestro conocimiento sobre la evolution del cáncer colorrectal.

[1]  M. Filipe,et al.  Abnormal patterns of mucus secretion in apparently normal mucosa of large intestine with carcinoma , 1974, Cancer.

[2]  R. Richart,et al.  Comparative electron-microscopic features of normal, hyperplastic, and adenomatous human colonic epithelium. II. Variations in surface architecture found by scanning electron microscopy. , 1973, Gastroenterology.

[3]  H. Spjut,et al.  The small carcinoma of the large bowel. , 1979, The American journal of surgical pathology.

[4]  E. Deschner,et al.  Kinetic and morphologic alterations in the colon of a patient with multiple polyposis , 1981, Cancer.

[5]  Deschner Ee.  Early proliferative changes in gastrointestinal neoplasia. , 1982 .

[6]  C. Williams,et al.  Practical Aspects of Endoscopic Management of Malignant Polyps , 1987, Endoscopy.

[7]  J. Mecklin,et al.  Histopathology of colorectal carcinomas and adenomas in cancer family syndrome , 1986, Diseases of the colon and rectum.

[8]  M. Hutt,et al.  The georgraphical pathology of bowel cancer and some related diseases. , 1971, Proceedings of the Royal Society of Medicine.

[9]  J. Jass.  RELATION BETWEEN METAPLASTIC POLYP AND CARCINOMA OF THE COLORECTUM , 1983, The Lancet.

[10]  E. Lally,et al.  Localization of free secretory component in pleomorphic adenomas of minor salivary gland origin , 1984, Cancer.

[11]  J. Madara,et al.  Evidence for an adenoma-carcinoma sequence in dimethylhydrazine-induced neoplasms of rat intestinal epithelium. , 1983, The American journal of pathology.

[12]  R. Pascal,et al.  Comparative electron microscopic features of normal, hyperplastic, and adenomatous human colonic epithelium. Variations in cellular structure relative to the process of epithelial differentiation. , 1973, Gastroenterology.

[13]  L. Ackerman,et al.  Small primary adenocarcinomas of the colon and rectum. , 1962, JAMA.

[14]  S. H. Rider,et al.  Chromosome 5 allele loss in human colorectal carcinomas , 1987, Nature.

[15]  F. C. Lucibello,et al.  Localization of the gene for familial adenomatous polyposis on chromosome 5 , 1987, Nature.

[16]  T. Eide,et al.  The age-, sex-, and site-specific occurrence of adenomas and carcinomas of the large intestine within a defined population. , 1986, Scandinavian journal of gastroenterology.

[17]  B. Vogelstein,et al.  Clonal analysis of human colorectal tumors. , 1987, Science.

[18]  N. Shepherd,et al.  Epithelial Misplacement in Peutz-Jeghers Polyps: A Diagnostic Pitfall , 1987, The American journal of surgical pathology.

[19]  M. Vatn,et al.  The prevalence of polyps of the large intestine in Oslo: An autopsy study , 1982, Cancer.

[20]  P. Sherlock.  Precancerous Lesions of the Gastrointestinal Tract , 1983 .

[21]  J. Jass,et al.  Histochemistry of epithelial metaplasia and dysplasia in human stomach and colorectum. , 1984, Scandinavian journal of gastroenterology. Supplement.

[22]  T. Muto,et al.  Small “flat adenoma” of the large bowel with special reference to its clinicopathologic features , 1985, Diseases of the colon and rectum.

[23]  H. Lynch,et al.  Hereditary proximal colonic cancer , 1977, Diseases of the colon and rectum.

[24]  D. Sheer,et al.  The isolation and characterization of colorectal epithelial cell lines at different stages in malignant transformation from familial polyposis coli patients , 1984, International journal of cancer.

[25]  Robert H. Collins,et al.  Colon cancer, dysplasia, and surveillance in patients with ulcerative colitis. A critical review. , 1987, The New England journal of medicine.

[26]  Chang Ww.  Histogenesis of colon cancer in experimental animals. , 1984 .

[27]  O. Sasaki,et al.  Mucinous carcinoma of the rectum , 1987, Histopathology.

[28]  E. C. Hammond,et al.  Adenomatous lesions of the large bowel: An autopsy survey , 1979, Cancer.

[29]  L. Ackerman,et al.  Distribution of colonic polyps: increased incidence of proximal lesions in older patients. , 1985, Radiology.

[30]  H. Nava,et al.  Small primary de novo adenocarcinoma of the colon with mesenteric lymphatic metastasis , 1983, Journal of surgical oncology.

[31]  T. Rognum,et al.  Plasma carcinoembryonic antigen concentrations and immunohistochemical patterns of epithelial marker antigens in patients with large bowel carcinoma. , 1982, Journal of clinical pathology.

[32]  A. Maskens,et al.  Experimental adenomas and carcinomas of the large intestine behave as distinct entities: Most carcinomas arise de novo in flat mucosa , 1981, Cancer.

[33]  M. Lipkin,et al.  Proliferative patterns in colonic mucosa in familial polyposis , 1975, Cancer.

[34]  H. Bussey,et al.  Juvenile polyposis–a precancerous condition , 1988, Histopathology.

[35]  E. Deschner,et al.  Significance of the labeling index and labeling distribution as kinetic parameters in colorectal mucosa of cancer patients and DMH treated animals , 1982, Cancer.

[36]  D W Day,et al.  Polyps and cancer of the large bowel: a necropsy study in Liverpool. , 1982, Gut.

[37]  F. Duckert.  Behaviour of antithrombin 3 in liver disease. , 1973, Scandinavian journal of gastroenterology. Supplement.

[38]  K. S. Bhangoo.  Letter: Rate of wound healing. , 1974, Lancet.

[39]  J. Stewart,et al.  The tumour promoter 12-O-tetradecanoylphorbol-13-acetate increases the activities of some peroxisome-associated enzymes in in vitro cell culture. , 1986, British Journal of Cancer.

[40]  T. Berge,et al.  Carcinoma of the colon and rectum in a defined population. An epidemiological, clinical and postmortem investigation of colorectal carcinoma and coexisting benign polyps in Malmö, Sweden. , 1973, Acta chirurgica Scandinavica. Supplementum.

[41]  B. Vogelstein,et al.  Prevalence of ras gene mutations in human colorectal cancers , 1987, Nature.

[42]  S. Halter,et al.  De novo carcinoma of the rectum: a case report. , 1985, The American journal of gastroenterology.

[43]  K. Vellacott,et al.  Colonic polyps complicating ureterosigmoidostomy , 1980, Histopathology.

[44]  V. Gilbertsen,et al.  The prevention of invasive cancer of the rectum , 1978, Cancer.

[45]  B C Morson,et al.  Factors influencing the prognosis of early cancer of the rectum. , 1966, Proceedings of the Royal Society of Medicine.

[46]  K. Chan,et al.  Polyps and diverticula of the large intestine: a necropsy survey in Hong Kong. , 1985, Gut.

[47]  K. Sugihara,et al.  Colorectal goblet cell mucins in familial adenomatous polyposis. , 1987, Journal of clinical pathology.

[48]  Love Rr.  Adenomas are precursor lesions for malignant growth in nonpolyposis hereditary carcinoma of the colon and rectum. , 1986 .

[49]  T. Muto,et al.  The evolution of cancer of the colon and rectum , 1974, Cancer.

[50]  N. Marcon,et al.  Mixed hyperplastic adenomatous polyps--an underdiagnosed entity. Report of a case of adenocarcinoma arising within a mixed hyperplastic adenomatous polyp. , 1984, The American journal of surgical pathology.

[51]  S. Hamilton,et al.  Colorectal carcinoma in patients with Crohn's disease. , 1985, Gastroenterology.

[52]  Sunter Jp.  Cell proliferation in gastrointestinal carcinogenesis. , 1984 .

[53]  A J Krush,et al.  Increased risk of cancer in the Peutz-Jeghers syndrome. , 1987, The New England journal of medicine.

[54]  J. Jass,et al.  DNA content and the adenoma-carcinoma sequence in the colorectum. , 1986, Journal of clinical pathology.

[55]  F. Konishi,et al.  Pathology of colorectal adenomas: a colonoscopic survey. , 1982, Journal of clinical pathology.

[56]  G. Williams.  Transitional mucosa of the large intestine , 1985, Histopathology.

[57]  J. Martínez-Peñuela,et al.  Hyperplastic polyposis of the colorectum and adenocarcinoma in a 24-year-old man. , 1987, The American journal of surgical pathology.

[58]  E. A. Jones,et al.  Mucinous adenocarcinoma in anorectal fistulae , 1984, Histopathology.

[59]  A. Balmain,et al.  Immunocytochemical demonstration of p21 ras family oncogene product in normal mucosa and in premalignant and malignant tumours of the colorectum. , 1985, British journal of cancer.

[60]  B. Dutrillaux,et al.  Consistent deficiencies of chromosome 18 and of the short arm of chromosome 17 in eleven cases of human large bowel cancer: a possible recessive determinism. , 1985, Annales de genetique.

[61]  Randall G. Lee,et al.  Dominant inheritance of adenomatous colonic polyps and colorectal cancer. , 1985, The New England journal of medicine.