Several previous studies have demonstrated that the CDX2-negative (CDX2) and/or CK20-negative (CK20) phenotypes of colorectal cancers (CRCs) might be associated with high levels of microsatellite instability (MSI-H). The aim of this study was to investigate the clinicopathologic and molecular features of MSI-H CRCs with different CDX2/CK20 expression statuses. The CDX2 and CK20 expression statuses were immunohistochemically evaluated in 109 MSI-H CRC tissue samples, and the correlations of these statuses with clinicopathologic, molecular, and survival data were statistically analyzed. Of the 109 MSI-H CRCs, 15 were CDX2 (13.8%), and 19 were CK20 (17.4%). The simultaneous loss of CDX2 and CK20 expression (CDX2/CK20) was observed in 9 cases (8.3%). CDX2 loss was correlated with lymph node metastasis, poor differentiation, MLH1 loss, the mutation of BRAF, and CpG island methylator phenotype-high (CIMP-H) status. Right-sided tumor location, nodal metastasis, poor differentiation, and CIMP-H status were significant characteristics of CK20 tumors. The CDX2/CK20 phenotype was associated with older age (above 56 y), higher stage (stage III or IV), deep invasion (pT3 or pT4), lymph node metastasis (pN1 or pN2), poor differentiation (nonmedullary/non-signet ring cell type), the mutation of BRAF, and CIMP-H status among MSI-H CRCs. Patients with CDX2/CK20 tumors exhibited worse overall and disease-free survival compared with the patients with CDX2 and/or CK20 tumors (P<0.001). In the multivariate analysis for disease-free survival, the CDX2/CK20 phenotype was an independent prognostic factor for MSI-H CRC (P=0.030, hazard ratio=3.288). The CDX2/CK20 phenotype defines a distinct subgroup of MSI-H CRCs with poor differentiation, CIMP-H status, and unfavorable prognosis.

It has been recently suggested that the expression levels of mutant HSP110 could be a prognostic marker in colorectal cancer with a high level of microsatellite instability (MSI-H). The aim of our study was to validate the prognostic significance of HSP110 mutation using immunohistochemistry and DNA testing in MSI-H colorectal cancer. Wild-type HSP110 (HSP110wt)-specific immunohistochemistry was performed in 168 MSI-H colorectal cancer tissues, and their expression levels were evaluated using a four-tier scoring system (0/1 þ /2 þ /3 þ ). Of these tissues, 167 cases were analyzed for HSP110 T 17 deletion. Associations with clinicopathological, molecular and survival parameters were statistically analyzed. The low-level expression of HSP110wt (0/1 þ ) was observed in 40 MSI-H colorectal cancers (24%) and was significantly related to large HSP110 T 17 deletions (Z 4 bp, Po0.001). In survival analysis, patients with low HSP110wt expression (0/1 þ ) showed better diseasefree survival compared with those with high expression (2 þ /3 þ ; P ¼ 0.005). This significance in survival difference was maintained in patients with 5-fluorouracil-based chemotherapy-treated tumors (P ¼ 0.024) and in those with stage III/IV tumors (P ¼ 0.032). Multivariate analysis confirmed the role of HSP110wt expression as an independent prognostic factor (P ¼ 0.016, hazard ratio ¼ 4.32). In MSI-H colorectal cancer, a low expression of HSP110wt is associated with large HSP110 T 17 deletions and better clinical outcome. Immunohistochemistry of HSP110wt can be a simple and valuable tool for the prognostic and therapeutic stratification of patients with MSI-H colorectal cancer.

KRAS mutation has an adverse prognostic impact on stage II or III CRC treated with adjuvant FOLFOX.

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Background:Endoscopic ultrasound–guided fine needle aspiration cytology (EUS-FNAC) is currently the most commonly used procedure for obtaining cytologic specimens of the pancreas. It is accurate, minimally invasive, safe and cost-effective. However, there is discrepancy between cytological and surgical diagnoses. This study was aimed at evaluating the diagnostic accuracy of EUS-FNAC of the pancreas.Methods:We performed a retrospective review of 191 cases of pancreatic lesions initially diagnosed by EUS-FNAC with subsequent histological diagnosis between 2010 and 2012 in the Department of Pathology, Seoul National University Hospital. Cytologic and surgical diagnoses were categorized into five groups: negative, benign, atypical, malignant, and insufficient for diagnosis. Subsequently, 167 cases with satisfactory yield in both surgical and cytology specimens were statistically analyzed to determine correlations with diagnosis.Results:In comparison to surgical diagnoses, cytologic diagnoses were true-positive in 103 cases (61.7%), true-negative in 28 cases (16.8%), false-positive in 9 cases (5.4%), and false-negative in 27 cases (16.1%). The diagnostic accuracy was 78.4%, sensitivity was 79.2%, and specificity was 75.7%. The positive predictive value was 92.0%, and negative predictive value was 50.9%.Conclusions:EUS-FNAC has high accuracy, sensitivity, specificity and positive predictive value. Overcoming the limitations of EUS-FNAC will make it a useful and reliable diagnostic tool for accurate evaluation of pancreatic lesions.