Pathogenesis and Management of Serrated Polyps: Current Status and Future Directions

Hyperplastic or serrated polyps were once believed to have little to no clinical significance. A subset of these polyps are now considered to be precursors to colorectal cancers (CRC) in the serrated pathway that may account for at least 15% of all tumors. The serrated pathway is distinct from the two other CRC pathways and involves an epigenetic hypermethylation mechanism of CpG islands within promoter regions of tumor suppressor genes. This process results in the formation of CpG island methylator phenotype tumors. Serrated polyps are divided into hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The SSA/P and the TSA have the potential for dysplasia and subsequent malignant transformation. The SSA/Ps are more common and are more likely to be flat than TSAs. Their flat morphology may make them difficult to detect and thus explain the variation in detection rates among endoscopists. Challenges for endoscopists also include the difficulty in pathological interpretation as well surveillance of these lesions. Furthermore, serrated polyps may be inadequately resected by endoscopists. Thus, it is not surprising that the serrated pathway has been linked with interval cancers. This review will provide the physician or clinician with the knowledge to manage patients with serrated polyps.

Immunohistochemical expression of ki-67 and p53 in colorectal adenomas: a clinicopathological study

To evaluate the significance of P53 and Ki-67 expression as immunohistochemical markers in early detection of premalignant changes in different types of colorectal adenomas. Also, to correlate immunohistochemical expression of the two markers with different clinicopathological parameters including; age, and sex of the patient, type, site, size and grade of dysplasia of colorectal adenomas. Forty-seven polypectomy specimens of colorectal adenomas were retrieved from the archival materials of the Gastrointestinal and Hepatic Diseases Teaching Hospital in Baghdad from 2009-2010. Four ?m section specimens were stained by immunohistochemical technique with Ki-67 and P53 tumor markers. P-values<0.05 were considered statistically significant. Immunohistochemical expressions of Ki-67 and P53 had a significant correlation with the size and grade of dysplasia in colorectal adenomas. However, there was no significant correlation among the immunohistochemical expression of Ki-67 and P53 with the age and gender of the patient, and the type and site of colorectal adenomas. There was no significant correlation between Ki-67 and P53 expressions in colorectal adenomas. Villous adenomas of colorectum showed a significant correlation with the grade of dysplasia, while there was no significant correlation between size and site of colorectal adenoma with the grade of dysplasia. High grade dysplasia with significant positive immunohistochemical markers of Ki-67 and P53 could be valuable parameters for selecting from the total colorectal adenoma population, those most deserving of close surveillance in followup cancer prevention programs. It is closely linked with increasing age particularly in patients with a large size adenoma of villous component in their histology

Estudo imunohistoquímico das expressões: hMLH1, hMSH2 e Cox-2 em pólipos do cólon / Study of immunohistochemical expressions of: hMLH1, hMSH2 and Cox-2 in colon polyps

Estudaram-se 167 pólipos, 6 biópsias de mucosa colônica normal e 23 biópsias de adenocarcinomas colorretais coletados por via endoscópica no período de 2000 a 2004 no Hospital Geral da Faculdade de Medicina de Caxias do Sul, quanto à presença de alterações de imunoexpressão do hMLH1, hMSH2 e Cox-2. Houve alteração na imunoexpressão do hMLH1 em por cento, hMSH2 em por cento e Cox-2 em por cento dos adenomas, respectivamente. Não houve associação entre as imunoexpressões e o sexo, idade, localização da lesão, histologia ou displasia. A imunoexpressão para o Cox-2 associou-se ao aumento do número de adenomas no mesmo paciente. As alterações de imunoexpressões de hMLH1 e Cox-2 em adenomas e adenocarcinomas de cólon, em pacientes sem história familial de câncer colorretal, são eventos relativamente freqüentes...

The aim of this study was the immunohistochemical expressions hMLH1, hMSH2 and Cox-2 in ressected colon polyps through endoscopy to check alterations in lesions that can be labeled as premature in the carcinogenesis of colorectal cancer. Moreover, the aim was to examine a possible association among the variables: age, sex, localization, size, histology and dysplasia grade. Prospectively, 167 colon polyps were ressected through endoscopies between the years 2000 and 2004 at the Digestive Endoscopy Department of Hospital Geral da Faculdade de Medicina in Caxias do Sul. Six normal colonical mucosa biopsies and 23 biopsies of colorectal adenocarcinomas from different segments were collected. All the material was studied through histopathology and immunohistochemistry. In the tubular adenomas there was loss of expression of the hMLH1 in 37.1 per cent and in 14.5 per cent there was loss of expression of the hMSH2. The Cox-2 was shown to be altered in 7 per cent of the tubular adenomas. There was no loss of expression of the genes hMLH1 e hMSH2 in the villous adenomas; however, the Cox-2 was shown to be altered in 100 per cent of the villous adenomas. In the tubular-villous adenomas there was loss of expression of the hMLH1 in 17.6 per cent and loss of 28.6 per cent of expression of the hMSH2...

Rastreamento do câncer colorretal: artigo de revisäo / Sreening and colorectal cancer: review

Os autores revisam e apresentam os principais métodos de rastreamento populacional para os adenomas colônicos e o câncer colorretal (CCR). A pesquisa de sangue oculto nas fezes pelo método guaiac é um procedimento sensível e específico de rastreamento, principalmente quando é utilizada a reidrataçäo das fezes. É um teste bem estudado em populaçöes assintomáticas, aplicável em nosso meio por ser de fácil utilizaçäo e baixo custo. A retossigmoidoscopia deve ser realizada a cada 3 anos, preferencialmente associada ao teste anual de pesquisa de sangue oculto nas fezes. O exame com aparelho flexível de 60 cm é preferível por ser menos incômodo ao paciente e oferecer alcance diagnóstico a cerca de metade dos CCR. A colonoscopia é um método eficaz e de baixo índice de morbidade, porém tem seu custo elevado, devendo ser indicada apenas em casos selecionados. O grande avanço alcançado nos últimos anos no campo da biologia molecular tornou possível, além do conhecimento do processo de carcinogênese do CCR, a detecçäo de células do epitélio colônico com alteraçöes genéticas descamadas nas fezes. Essas mutaçöes predispöem ao aparecimento do CCR. Os autores também mostram fatores de risco para o desenvolvimento do CCR, como idade acima de 50 anos, retocolite ulcerativa inspecífica, doença de Crohn, antecedentes familiares e pessoais de pólipos e CCR.

Expresion de p53 y de bcl-2 en adenomas y carcinomas colorrectales / Expression of p53 and bcl-2 in colorectal adenomas and carcinomas

Trabajos recientes han asociado a los genes p53 y bcl-2 en el proceso de la transformación neoplásica. Dado que la secuencia adenoma-carcinoma en el colon y recto es un buen modelo natural de carcinogénesis, consideramos de interes analizar la expresión de bcl-2 y de p53 en estas neoplasias. Se estudiaron 73 pólipos adenomatosos (adenomas) y 60 adenocarcinomas de colon y recto. De los adenomas 16 tenían displasia leve, 27 moderada, 15 severa y en 15 había carcinoma focal. Todos los adenocarcinomas sobrepasaban la muscular propia y eran moderadamente diferenciados. La expresión de los genes se analizó por inmunohistoquímica utilizando al anticuerpo bcl-2 de Dako y el anticuerpo p53 de Novocastra. Los resultados mostraron que hubo acumulación de proteína p53 en 34/73 (46 por ciento)del total de los adenomas y en 47/60 (78 por ciento) de los adenocarcinomas ( p= 0,0001). El conjunto de adenomas con displasia mostró una reactividad de 26/58 (45 por ciento), similar a 8/15 (53 por ciento, p = 0,4) de los adenomas con carcinoma focal, aunque diferente a la de los adenocarcinomas, 47/60 (78 por ciento, p = 0,0001). Con referencia al bcl-2, 53/73 (73 por ciento) del total de los adenomas lo expresaban mientras que en los adenocarciomas la expresión se observó en 14/60 (23 por ciento, p = 0,0000). En los adenomas sin carcinoma se encontró una expresión de 47/58 (81 por ciento) que comparada con la observada en los adenomas con carcinoma focal, 6/15 (40 por ciento), y con adenocarcinoma, 14/60 (23 por ciento), mostraron diferencias estadísticamente significativas (p = 0,001 y p + 0,0000 respectivamente). Cuando se analizó la frecuencia de expresión de los dos genes estudiados en las diferentes neoplasias se observó entre ellos una relación inversa. Este trabajo permite concluir que la expresión de bcl-2 es un evento temprano en la carcinogénesis y que es reemplazado por la mutación de p53 al progresar la neoplasia.