Magnifying Colonoscopy Findings for Differential Diagnosis of Sessile Serrated Adenoma/Polyps and Hyperplastic Polyps

Sessile serrated adenoma/polyps (SSA/Ps) are thought to be precursors of colorectal cancers. However, current endoscopic techniques for differentiating SSA/Ps from conventional hyperplastic polyps (HPs) have low diagnostic accuracy. The aim of the present study was to assess the ability of mucosal crypt patterns to distinguish SSA/Ps from HPs. We examined 140 lesions from 93 patients that had been diagnosed histologically as SSA/Ps or HPs at the Showa University Hospital between June 2010 and May 2012. Three experienced colonoscopists reviewed the endoscopic findings of magnifying colonoscopy. Type II open-shape (Type II-O) pit patterns and varicose microvascular vessels (VMVs) were identified according to previously proposed definitions. Although 140 lesions were initially identified for the study, 27 lesions were excluded from analysis because of insufficient endoscopic findings. Thus, endoscopic findings from a total of 113 lesions (68 SSA/Ps and 45 HPs) were evaluated. Of 113 serrated polyps, 51 lesions (44 SSA/Ps and 7 HPs; P<0.01) had Type II-O pit patterns. The inter- and intra-observer agreement for these patterns among three colonoscopists was κ=0.61 (range 0.57–0.65) and κ=0.68 (range 0.52–0.94), respectively. The positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of Type II-O pit patterns for differentiating between SSA/P and HP were 86%, 61%, 65%, and 84%, respectively. In contrast, the PPV, NPV, sensitivity, and specificity of VMVs were 68%, 43%, 37%, and 73%, respectively. The results indicate that Type II-O mucosal crypt patterns may be useful for the differential diagnosis of SSAPs and HPs

Isolation of a Novel Human Gene, MARKLI, Homologous to MARK3 and Its Involvement in Hepatocellular Carcinogenesis

Activation of the Writ-signaling pathway is known to play a crucial role in carcinogenesis of various human organs including the colon, liver, prostate, and endometrium. To investigate the mechanisms underlying hepatocellular carcinogenesis, we attempted to identify genes regulated by β-catenin/Tcf complex in a human hepatoma cell line, HepG2, in which an activated form of β-catenin is expressed. By means of cDNA microarray, we isolated a novel human gene, termed MARKLI (MAP/microtubule affinity-regulating kinase-like 1), whose expression was downregulated in response to decreased Tcf/LEF1 activity. The transcript expressed in liver consisted of 3529 nucleotides that contained an open reading frame of 2256 nucleotides, encoding 752 amino acids homologous to human MARK3 (MAP/ microtubule affinity-regulating kinase 3). Expression levels of MARKL1 were markedly elevated in eight of nine HCCs in which nuclear accumulation of β-catenin was observed, which may suggest that MARKL1 plays some role in hepatocellular carcinogenesis

Clinicopathological and Molecular Features of Laterally Spreading Tumors

Colorectal flat-elevated neoplasms can be classified into small-flat adenoma and laterally spreading tumors (LSTs), which can then be sub-categorized into granular-type (LST-G) and nongranular-type (LST-NG) LSTs with possible biological differences between them. We evaluated clinicopathological features and KRAS / BRAF mutations in 24 LST-Gs and 57 LST-NGs. PCR-based pyrosequencing assays were used to determine the presence of activating mutations in codons 12 and 13 of KRAS and in codon 600 of BRAF. Significant differences between LST-Gs and LST-NGs were observed in tumor size (30mm vs. 15mm, P<0.0001) and the frequency of KRAS mutations (75%, 18/24 vs. 5%, 3/57, P< 0.0001). For LST-NGs, the histological grade was increased with an increase in the tumor size. The frequency of submucosal cancer (SM-ca) was also higher in tumors of at least 20mm than in tumors smaller than 20mm (P<0.05). In contrast, there was no indication of a size-dependent increase in the histological grade. No significant difference in the frequency of KRAS mutation in LST-Gs and LST-NGs was related to tumor size. Two subtypes of LSTs were observed to have different clinicopathological and molecular characteristics. These findings suggest that different molecular mechanisms could exist in these subtypes of colorectal flat-type neoplasms