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Serrated lesions in the colorectum are currently predominantly classified as hyperplastic polyps (HPs), sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs) according to their morphology. However, the histological morphology and the molecular changes in the serrated lesions are still unclear. We performed immunohistochemistry for Ki67, p16INK4a, and WNT5A in human HPs (n=22), SSA/Ps (n=41), and TSAs (n=19). The distribution of Ki67 and p16INK4a positive cells in TSAs was different from that in HPs and SSA/Ps. Co-expression of Ki67 and P16INK4a was infrequent in HPs and SSA/Ps; p16INK4a-positive cells were found in the crypt cleft and stromal WNT5A-positive stromal cells were localized near the cleft in SSA/Ps, while intraepithelial lymphocytes (IELs) in SSA/Ps were more abundant than HPs. In conclusion, our study provides evidence that HPs branch because of the increase in and patchy distribution of senescent and proliferative cells, with increased and misdistributed stromal and inflammatory cells, which might contribute to creation of L- and/or T-shaped crypts, which are of distinctive shapes in SSA/Ps. Our findings may facilitate better understanding and therapy in the serrated lesions.

Recent studies have shown that promoter hypermethylation of tumor suppressor genes is an important factor in carcinogenesis of several human organs. The purpose of this study was to examine the methylation status of CHFR, a novel cell cycle regulatory gene, in both primary oral cancer tumors and the adjacent normal mucosa, and to clarify the relation between the methylation status and expression of the CHFR-related chromosomal passenger protein Aurora-A. The methylation status of the CHFR gene was examined by the methylation-specific PCR (MSP) in 49 primary oral squamous cell carcinomas (OSCC) and 6 OSCC cell lines. In 13 cases, the adjacent normal oral mucosal tissues were also examined. Normal oral mucosa from 18 healthy volunteers was used as the control. The mRNA level of Aurora-A and CHFR in OSCC cell lines was investigated by real-time RT PCR and the protein expression of Aurora-A in certain tumor samples was confirmed by immunohistochemistry. Aberrant promoter methylation of the CHFR gene was detected in 34.7% (17 of 49) of OSCC cases. As for the 13 OSCC cases with paired cancerous and adjacent normal tissues, promoter hypermethylation of the CHFR gene was detected in 46.1% (6 of 13) of the cancerous tissues. In contrast, promoter hypermethylation of the CHFR gene was recognized in only 7.7% (1 of 13) of the surrounding normal mucosa. No hypermethylation of the CHFR gene was detected in healthy volunteers. Only one OSCC cell line shows hypermethylation of the CHFR gene with concurrently silenced mRNA expression, however, Aurora-A was expressed abundantly in all cell lines. Furthermore, there is no significant relationship between methylation status of the CHFR gene and Aurora-A protein expression in OSCC. Hypermethylation of the CHFR gene was detected in a certain part of OSCC cases whereas it had very low frequency in adjacent normal oral tissues. Although further study is needed, Aurora-A gene expression seems to be independent from methylation status of the CHFR gene in OSCC.