RESUMO
AIMS: The incidence and mortality rates from right-sided colorectal cancers (CRCs) have not decreased in recent years. It is very likely that a significant proportion of these cancers evolve from undetected sessile serrated adenomas (SSAs). The prevalence and molecular features of the SSAs in the Chinese population have seldom been investigated. METHODS: We retrospectively reviewed the colonoscopy database and pathology archives in our medical centre. Adenomatous polyposis coli (APC) and ß-catenin expressions were examined in 28 right hyperplastic polyps (RHPs) and 21 SSAs by immunohistochemical staining. The mutations of BRAF, KRAS, APC and ß-CATENIN were analysed by direct sequencing. The methylation status of APC promoter in these polyps was analysed by methylation-specific PCR and bisulfite sequencing. Samples of left hyperplastic polyps, traditional adenomas and CRC were used as controls. RESULTS: SSAs accounted for 4.9% of serrated polyps and 1.0% of all colorectal polyps. BRAF((V600E)) mutations were found in 14.3% of SSAs and 7.1% of RHPs. Nuclear accumulation of ß-catenin was seen in 28.6% of SSAs and 17.9% of RHPs. APC mutations were detected in 57.1% of SSAs and 67.9% of RHPs. APC methylation was detected in 14.3% of RHPs and 23.8% of SSAs. CONCLUSIONS: The prevalence of SSAs in a subset of the Chinese population is much lower than that in the Western population. BRAF((V600E)) mutation is not a frequent event in right colon serrated polyps in a subset of the Chinese population. APC mutation is possibly the main cause for the Wnt signalling activation in right colon serrated polyps.
Assuntos
Adenoma/etnologia , Adenoma/genética , Povo Asiático/genética , Biomarcadores Tumorais/genética , Pólipos do Colo/etnologia , Pólipos do Colo/genética , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/genética , Adenoma/química , Adenoma/classificação , Adenoma/patologia , Proteína da Polipose Adenomatosa do Colo/análise , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biópsia , China/epidemiologia , Pólipos do Colo/química , Pólipos do Colo/classificação , Pólipos do Colo/patologia , Colonoscopia , Neoplasias Colorretais/química , Neoplasias Colorretais/classificação , Neoplasias Colorretais/patologia , Metilação de DNA , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Valor Preditivo dos Testes , Prevalência , Prognóstico , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , beta Catenina/análise , beta Catenina/genética , Proteínas ras/genéticaRESUMO
The role of the Wnt signaling pathway in the tumorigenesis of sessile serrated adenoma (SSA) of the colorectum remains controversial. Using 2 antibodies targeting different epitopes (C-terminus and N-terminus), ß-catenin expression in 35 SSAs and 30 right-sided hyperplastic polyps (RHPs) was examined by immunohistochemistry. Samples of 10 normal colorectal mucosa, 32 left-sided hyperplastic polyps, 27 traditional serrated adenomas (TSAs), and 40 traditional adenomas (TAs) were used as controls. Expression of adenomatous polyposis coli (APC) and mutated in colorectal cancer (MCC), key regulators of ß-catenin, was also examined by immunohistochemistry. Using the C-terminus antibody, no nuclear staining of ß-catenin was observed in any SSAs or RHPs. However, with the N-terminus antibody, accumulation of ß-catenin was seen in 40.0% of SSAs and 33.3% of RHPs. The average immunoreactivity score of APC in SSAs (67.0 ± 21.6) and RHPs (69.2 ± 24.4) was significantly higher than that in TAs (22.0 ± 18.0) and TSAs (49.5 ± 23.1; all P < .05). In contrast, MCC was more frequently lost in right-sided-polyps such as SSA and RHP than in left-sided polyps such as left-sided hyperplastic polyp, TSA, and TA. Our results suggest that Wnt signaling is activated in SSA and its possible precursor lesion RHP. The present study also implied that the specific molecular form of ß-catenin may participate in the Wnt signaling activation of right-sided serrated polyps. Moreover, loss of MCC expression but not APC may contribute to the early activation of Wnt signaling in right-sided serrated polyps.
