Are clinicopathological features of colorectal cancers with methylation in half of CPG island methylator phenotype panel markers different from those of CPG island methylator phenotype-high colorectal cancers?

Abstract

in 15/16 (93.7%) cases, including CK20, mostly 'dot-like' (12/13, 92.3%); CK (6/7, 85.7%), AE1/AE3 (3/3, 100%) and CK7 (1/6, 16.6%), along with neuroendocrine markers (16/16, 100%), including synaptophysin (11/13, 84.6%), chromogranin (12/15, 80%) and CD56 (4/4, 100%). Other positive IHC marker was CKIT/CD117 (3/3). Surgical resection was performed in 11/11 (100%) cases, with adjuvant chemotherapy offered in a single case. On follow-up (n=4 cases), two cases with large-sized tumours developed lymph node metastasis, including 1 who also developed pulmonary metastasis. Two patients were free-ofdisease (16 months, 21 months) and 2 were alive-with-disease. Conclusions: MCCs exhibit a wide histopathological spectrum, including co-existing Bowen's and rhabdomyoblastic de-differentiation. Careful analysis of key histopathological features and optimal IHC results with CK20, synaptophysin, chromogranin and CD56 are helpful in a timely diagnosis, as these are aggressive. MCCs also express CKIT.

Dabrafenib, a selective BRAFV600E inhibitor, is not able to reverse the CpG island methylator phenotype in RKO colorectal cell line

“…CRC cell lines have been used extensively to map the molecular mechanisms of carcinogenesis as they, according to integrated studies, demonstrate similar genetic and epigenetic aberrations to primary tumors (6)(7)(8). During the last years, research is focused on the serrated neoplasia pathway characterizing the progression of sessile serrated adenomas or traditional serrated adenomas into invasive adenocarcinomas (9)(10)(11). This particular molecular pathway of carcinogenesis is associated with female in older age predominance, proximal colon location, BRAF mutation, microsatellite instability (MSI), CIMP high (CIMP-H) and poor differentiation (9).…”

“…During the last years, research is focused on the serrated neoplasia pathway characterizing the progression of sessile serrated adenomas or traditional serrated adenomas into invasive adenocarcinomas (9)(10)(11). This particular molecular pathway of carcinogenesis is associated with female in older age predominance, proximal colon location, BRAF mutation, microsatellite instability (MSI), CIMP high (CIMP-H) and poor differentiation (9). Prognosis and overall survival of these tumors with MSI and CIMP-H, harboring BRAF mutation is poor making an effective targeted molecular therapy crucial (2,12,13).…”