Aberrant expression of annexin A10 is closely related to gastric phenotype in serrated pathway to colorectal carcinoma

Abstract

Annexin A10 (ANXA10) is a member of the ANX family that is normally expressed in gastric mucosa. ANXA10 was recently observed to be upregulated in sessile serrated adenoma, a precursor to microsatellite-unstable colorectal cancer. We investigated the use of ANXA10 in diagnosing colorectal carcinoma. In an immunohistochemical analysis, the intensity and quantity of ANXA10, MUC5AC, MUC6 and CDX2 in 123 colorectal carcinomas were graded. We determined the molecular status of BRAF and KRAS mutations, as well as the microsatellite instability status and the CpG island methylator phenotype in all colorectal carcinomas, and subcategorized into four molecular subgroups according to the molecular derangements. Nuclear ANXA10 staining was present in 36 colorectal carcinomas, exhibiting a strong significant association with the BRAF mutation status (Po0.0001) and positive CpG island methylator phenotype (Po0.0001), and a borderline significant association with high levels of microsatellite instability (P ¼ 0.072). The ANXA10-positive colorectal carcinomas were frequently positive for MUC5AC and MUC6, and were associated with absent or reduced CDX2 expression (all Po0.0001). According to a classification and regression tree analysis, ANXA10 is a superior marker for the molecular subtyping of colorectal carcinomas and represents a specific marker for colorectal cancers of the serrated pathway. Our results indicated that ANXA10 expression is implicated in gastric programming in serrated-pathway-associated colorectal carcinoma. ANXA10-positive colorectal carcinoma is highly associated with the molecular features of the serrated neoplasia pathway.

Annexin A10 is a candidate marker associated with the progression of pancreatic precursor lesions to adenocarcinoma

“…Aberrant ANXA10 expression has been reported to be closely associated with adenocarcinomas of the gastric and pancreatobiliary system [17, 24] as well as colorectal carcinoma (CRC) [16, 25–26]. The ANXA10 expression was highly related to gastric phenotype in the serrated pathway to colorectal carcinoma [16] and associated with poor prognosis in CRCs [25].…”

“…Cell surface ANXA2 expression was shown to be strongly upregulated during the progression from low-grade PanIN lesions to pancreatic adenocarcinoma [15]. Increased expression of ANXA10 was closely related to a gastric phenotype in serrated pathway to colorectal carcinoma [16] while the downregulation of ANXA10 was correlated with tumor progression in intestinal-type gastric carcinoma [17]. Compared to the other 12 members in human ANXA family, ANXA10 has distinct features including an unusual single codon deletion and loss of two main type II calcium-binding sites [9, 18], which could result in different functional consequences.…”

FrequentBRAFmutation in early-onset colorectal cancer in Taiwan: association with distinct clinicopathological and molecular features and poor clinical outcome

“…Mismatch repair (MMR) protein immunohistochemistry, KRAS exon 2 and BRAF exon 15 mutation, MSI and CIMP analyses were performed using the same methods as previously described 21 22…”

CpG Island Methylator Phenotype May Predict Poor Overall Survival of Patients with Stage IV Colorectal Cancer

“…After purification, direct sequencing was performed using an automated ABI 3730 sequencer (Applied Biosystems, Foster City, CA, USA). The detailed methods of KRAS and BRAF mutational analyses have been described in our previous study [17]. …”

“…The primers and probes used for the MethyLight study are listed in Table 1. The detailed methodology of CIMP determination has been described in our previous study [17]. CIMP-high CRC was designated when ≥3 methylated loci were identified, and CIMP-low/negative CRC was identified when < 3 methylated loci were found.…”