Distribution of the <i>COX-2 −1195</i> and <i>−765</i> genotypes and corresponding ORs in patients with IBD, CD or UC versus controls.

+<p>In the ulcerative colitis group, there are some missing data (n = 5) due to unsuccessful PCR for the <i>−765 G→C</i> polymorphism.</p><p>OR = Odds ratio; CI = confidence interval.</p

<i>COX-2</i> diplotype distribution and corresponding ORs in patients with IBD, CD or UC versus controls.

<p>OR = Odds ratio; CI = confidence interval.</p

Clinical characteristics of patients with Crohn's disease (n = 525).

+<p>Patients could be classified as having disease localisation in the upper gastrointestinal tract next to ileal, colonic or ileocolonic localisation.</p><p>*Note that data of patients are missing.</p

EMAST Is Associated with a Poor Prognosis in Microsatellite Instable Metastatic Colorectal Cancer

<div><p>Purpose</p><p>To determine the frequency and prognostic value of elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) in metastatic colorectal cancer (mCRC) patients in relation to microsatellite instability (MSI) status and MSH3 protein expression.</p><p>Material and Methods</p><p>The frequency of EMAST was evaluated in mCRC patients with MSI tumors and microsatellite stable (MSS) tumors. A literature overview was performed to compare the frequency of EMAST in our study with existing data. Immunohistochemistry for MSH3 was compared with EMAST status. Outcome was studied in terms of overall survival (OS) of mCRC patients with MSI and MSS tumors.</p><p>Results</p><p>EMAST was evaluated in 89 patients with MSI tumors (including 39 patients with Lynch syndrome) and 94 patients with MSS tumors. EMAST was observed in 45.9% (84 out of 183) of patients, with an increased frequency in MSI tumors (79.8% versus 13.8%, p < 0.001). We found no correlation between EMAST and MSH3 protein expression. There was no effect of EMAST on prognosis in patients with MSS tumors, but patients with MSI / non-EMAST tumors had a significantly better prognosis than patients with MSI / EMAST tumors (OS: HR 3.22, 95% CI 1.25-8.30).</p><p>Conclusion</p><p>Frequency of EMAST was increased in mCRC patients with MSI tumors, compared to MSS tumors. Our data suggest that the presence of EMAST correlates with worse OS in these patients. There was no effect of EMAST on the prognosis of patients with MSS tumors. A limitation of our study is the small number of patients in our subgroup analysis.</p></div

Diplotype-phenotype correlations in patients with Crohn's disease.

<p>Diplotype-phenotype correlations in patients with Crohn's disease in which the AG/AG diplotype served as reference.</p>+<p>Patients could be classified as having disease localisation in the upper gastrointestinal tract next to ileal, colonic or ileocolonic localisation.</p>*<p>For full notation see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015011#pone-0015011-t004" target="_blank">Table 4</a>.</p

Diplotype-phenotype correlations in patients with ulcerative colitis.

<p>Diplotype-phenotype correlations in patients with ulcerative colitis in which AG/AG served as reference.</p>#<p>For full notation see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0015011#pone-0015011-t004" target="_blank">Table 4</a>.</p

Flowchart of selected CRC patients to determine the frequency and prognostic value of EMAST.

<p>Flowchart of selected CRC patients to determine the frequency and prognostic value of EMAST.</p

Staining pattern of MSH3 protein expression.

<p>Heterogeneous MSH3 protein expression (A), demonstrated by expression of both brown (positive) and blue (negative) nuclei upon MSH3 IHC staining. Low MSH3 protein expression was defined as <85% brown staining of cell cores in tumor cells (B) and high MSH3 protein expression was defined as ≥85% brown staining of cell cores in tumor cells (C).</p

Prevalence of EMAST and non-EMAST tumors in the different patient groups.

<p><i>p</i> value represent heterogeneity between groups</p><p>Abbreviations: EMAST = elevated microsatellite alterations at selected tetranucleotide repeats, MSI = microsatellite instability, MSS = microsatellite stability</p><p>Prevalence of EMAST and non-EMAST tumors in the different patient groups.</p

Frequency of instable EMAST markers (A) and frequency of affected EMAST loci (B), subdivided by patients with MSI and MSS tumors.

<p>Frequency of instable EMAST markers (A) and frequency of affected EMAST loci (B), subdivided by patients with MSI and MSS tumors.</p