Intermediate serrated polyp as an intermediate lesion of hyperplastic polyp and sessile serrated polyp/adenoma in terms of morphological and molecular features.

Although a hyperplastic polyp (HP) shares morphological and molecular features with a sessile serrated adenoma/polyp (SSA/P), HPs and SSA/Ps are considered nonneoplastic and neoplastic epithelial polyps, respectively. Because HPs and SSA/Ps cover the morphological spectrum, we hypothesized that an intermediate serrated polyp (ISP) might exist between an HP and an SSA/P in terms of both morphological and molecular aspects. An ISP was defined as a serrated lesion that carries distorted crypts (columnar crypt dilation, irregularly branching crypts, or horizontally arranged basal crypts) in less than 3 consecutive crypts. We analyzed HPs (microvesicular, n = 16, and goblet cell-rich, n = 28), ISPs (n = 44), and SSA/Ps (n = 26) for their methylation status of 8 CpG island methylator phenotype panel markers and mutation status of KRAS/BRAF. The number of methylated markers and BRAF mutation frequency increased in the order of HP, ISP, and SSA/P. Microvesicular HPs and goblet cell-rich HPs are distinct from each other, based on the high frequency of BRAF and KRAS mutation, respectively, but are not different in the number of methylated panel markers. Proximally located microvesicular HPs and ISPs were higher in the number of methylated markers but lower in the frequency of BRAF mutation than distally located ones. However, SSA/Ps did not show any difference in the number of methylated markers and the frequency of BRAF mutation between proximally and distally located lesions. Our findings that serrated polyps, intermediate between HPs and SSA/Ps in terms of morphological features, display molecular alterations intermediate between those of HPs and SSA/Ps suggest the presence of ISPs between HPs and SSA/Ps.

Kwon HJ ，Cho NY ，Chang MS ，Kim YS ，Kang GH ... -  《-》

Molecular features of colorectal hyperplastic polyps and sessile serrated adenoma/polyps from Korea.

Kim KM ，Lee EJ ，Ha S ，Kang SY ，Jang KT ，Park CK ，Kim JY ，Kim YH ，Chang DK ，Odze RD ... -  《-》

BRAF and KRAS Mutations in hyperplastic polyps and serrated adenomas of the colorectum: relationship to histology and CpG island methylation status.

Yang S ，Farraye FA ，Mack C ，Posnik O ，O'Brien MJ ... -  《AMERICAN JOURNAL OF SURGICAL PATHOLOGY》

Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points.

O'Brien MJ ，Yang S ，Mack C ，Xu H ，Huang CS ，Mulcahy E ，Amorosino M ，Farraye FA ... -  《AMERICAN JOURNAL OF SURGICAL PATHOLOGY》

Reappraisal of the genetic heterogeneity of sessile serrated adenoma/polyp.

Sessile serrated adenoma/polyp (SSA/P) is regarded as a genetically homogeneous entity, with most lesions harbouring the BRAF V600E mutation. The present study aimed to reappraise the genetic heterogeneity of SSA/Ps and its clinicopathological significance. We performed next-generation sequencing of 272 SSA/Ps without dysplasia and evaluated morphological and molecular features associated with the respective genotypes. BRAF V600E, BRAF non-V600E, KRAS and NRAS mutations were found in 223 (82.0%), three (1.2%), 28 (10.3%) and one lesion (0.4%), respectively. Notably, all lesions with BRAF non-V600E mutations had either KRAS or NRAS mutations concurrently. Twenty SSA/Ps (7.4%) were negative for these mutations. KRAS-mutated SSA/Ps were located more often in the distal colon (42%) compared to those with the BRAF V600E mutation (14%). Histologically, minimally serrated crypts and goblet cell-rich crypts were more common in KRAS-mutated and mutation-negative SSA/Ps. However, in most instances, SSA/Ps lacking the BRAF V600E mutation were indistinguishable morphologically from those with the BRAF V600E mutation. MUC5AC and MUC6 expression was common regardless of the mutation status, but more extensive in SSA/Ps with the BRAF V600E mutation. CpG island methylator phenotype-high was more frequent in SSA/Ps with the BRAF V600E mutation (60%), followed by mutation-negative SSA/Ps (40%) and KRAS-mutated SSA/Ps (16%). The present study confirmed the common presence of the BRAF V600E mutation in SSA/Ps, but also demonstrated a degree of molecular heterogeneity of SSA/Ps. SSA/Ps with and without the BRAF V600E mutation showed slightly different but overlapping histological and molecular features.

Cho H ，Hashimoto T ，Yoshida H ，Taniguchi H ，Ogawa R ，Mori T ，Hiraoka N ，Saito Y ，Sekine S ... -  《-》