Increased risk for abnormalities on perioperative colon screening in patients with microsatellite instability–positive endometrial carcinoma

2006 ◽  
Vol 16 (6) ◽  
pp. 1980-1986 ◽  
Author(s):  
B. M. Buttin ◽  
M. A. Powell ◽  
P. J. Goodfellow ◽  
S. N. Lewin ◽  
R. K. Gibb ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Microsatellite Instability ◽  
Medical Records ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Molecular Stratification ◽  
Colon Cancers ◽  
Increased Risk ◽  
Primary Colon ◽  
Endometrial Cancers

Microsatellite instability (MSI) is a feature of certain hereditary and sporadic endometrial and colon cancers. We set out to determine whether molecular stratification of endometrial cancers based on tumor MSI status could help identify patients at increased risk for abnormalities found on perioperative colon screening. From a prospectively accrued series of 413 patients, medical records were reviewed from 94 patients with MSI positive (MSI+) and 94 patients with MSI negative (MSI−) endometrial cancers, matched by year of diagnosis. We reviewed clinicopathologic data and results of perioperative colon screening. Differences were analyzed using Fisher exact test and logistic regression analysis. There were no significant clinicopathologic differences between the two cohorts. Sixty-five percent of patients in each group underwent perioperative colon screening. However, patients with MSI+ cancers had a twofold increase in the frequency of colonic abnormalities (30% versus 14.8%, P= 0.044) over those with MSI− cancers. Furthermore, the only primary colon cancers (N= 2) were found in women with MSI+ endometrial cancers that were unmethylated at the MLH1 promoter. Our data suggest that patients with MSI+ endometrial cancers are at increased risk for abnormalities on perioperative colon screening. Those with MSI+MLH1 unmethylated cancers appear to be at highest risk.

scholarly journals Morphological Features and Prognostic Significance of ARID1A-Deficient Esophageal Adenocarcinomas

2017 ◽  
Vol 141 (7) ◽  
pp. 970-977 ◽  
Author(s):  
Michael G. Drage ◽  
Mingkhwan Tippayawong ◽  
Agoston T. Agoston ◽  
Yifan Zheng ◽  
Raphael Bueno ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Proportional Hazards ◽  
Prognostic Significance ◽  
Nodal Metastasis ◽  
Cox Proportional Hazards ◽  
Barrett Esophagus ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Increased Risk ◽  
Primary Driver

Context.— The clinicopathologic and prognostic significance of ARID1A mutation in esophageal adenocarcinoma (EAC) is unknown. Objective.— To determine the morphological correlates and prognostic significance of ARID1A-deficient EAC. Design.— One hundred twenty cases of primary EAC were evaluated for a predetermined set of histologic features and immunohistochemistry for ARID1A, p53, and MLH1 performed on EAC, as well as adjacent Barrett esophagus and Barrett esophagus–associated dysplasia, when feasible. Associations between categorical clinicopathologic variables were analyzed by Fisher exact test, and survival analysis was performed by a Cox proportional hazards analysis. Results.— The study group included 97 men and 23 women (mean age, 66 years). Loss of ARID1A expression was seen in 12 of 120 EACs (10%). ARID1A-deficient tumors showed a strong correlation with a medullary and mucinous phenotype, and 8 of 12 (67%) had at least one feature reminiscent of high microsatellite instability colon carcinomas (mucinous or medullary differentiation, marked intratumoral or peritumoral lymphoid infiltrate). A mutant p53 pattern was present in 52 of 120 EACs (43%) and showed no correlation with ARID1A deficiency (P > .05). MLH1 loss was present in only 2 of 120 EACs (2%); both of which were also deficient in ARID1A. ARID1A-deficient EACs showed a trend toward increased risk of nodal metastasis but had no effect on overall patient survival. Conclusions.— ARID1A-deficient EACs show a phenotype similar to colon cancer with high microsatellite instability but do not appear to have any prognostic significance. Concurrent MLH1 loss is not seen in most ARID1A-deficient tumors, suggesting that ARID1A may be a primary driver of carcinogenesis in a subset of EACs.

scholarly journals Determination of Clopidogrel Resistance by Whole Blood Platelet Aggregometry and Inhibitors of the P2Y12 Receptor

2006 ◽  
Vol 52 (3) ◽  
pp. 383-388 ◽  
Author(s):  
Boris T Ivandic ◽  
Philipp Schlick ◽  
Peter Staritz ◽  
Kerstin Kurz ◽  
Hugo A Katus ◽  
...  
Keyword(s):  
Whole Blood ◽  
Adenosine Monophosphate ◽  
Blood Platelet ◽  
P2y12 Receptor ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Clopidogrel Resistance ◽  
Impedance Aggregometry ◽  
Platelet Aggregometry ◽  
Increased Risk

Abstract Background: Inhibition of platelet aggregation by clopidogrel may be insufficient in up to 30% of users. These nonresponders carry an increased risk of cardiovascular events. We reported here a simple assay to study clopidogrel responsiveness. Methods: Electrical impedance aggregometry was performed in diluted whole blood in the presence of 5 and 20 μmol/L ADP. Some samples were incubated with 0.1 mmol/L methyl-S-adenosine monophosphate (MeSAMP), a P2Y12 receptor blocker, to maximize inhibition of aggregation before aggregometry. To validate the assay, we analyzed 6-min impedance in 21 healthy probands and 244 patients with coronary artery disease (CAD). Results: At 5 μmol/L ADP, the imprecision of the assay was 11%. Mean (SD) impedance of the healthy cohort was 12.2 (2.2) Ω. The mean − 3 SD was used to define the cutoff for clopidogrel responsiveness: responders and nonresponders exhibited a 6-min impedance ≤5 Ω and >5 Ω, respectively. Samples from nonresponders were incubated with MeSAMP and analyzed again to distinguish pharmacokinetic and pharmacodynamic types of resistance. Sixteen percent of CAD patients were classified as nonresponders (38 and 2 cases of pharmacokinetic and pharmacodynamic resistance, respectively). Female sex was strongly associated with clopidogrel resistance (P = 0.0002, Fisher exact test). A higher clopidogrel loading dose (P = 0.0353, Mann–Whitney U-test) was given to responders (median, 450 mg) than nonresponders (median, 300 mg). Age and cardiovascular diagnosis showed no significant associations. Conclusions: Impedance aggregometry using 5 μmol/L ADP is a useful tool for studying clopidogrel responsiveness. MeSAMP allows characterization of responsiveness “on treatment” and may be useful for optimizing clopidogrel dosing.

scholarly journals Polymorphisms in Phase I (CYP450) Genes CYP1A1 (rs4646421), CYP1B1 (rs1056836), CYP19A1 (rs749292) and CYP2C8 (rs1058930) and Their Relation to Risk of Breast Cancer: A Case-Control Study in Mazandaran Province in North of Iran

2019 ◽  
Vol 7 (15) ◽  
pp. 2488-2496 ◽  
Author(s):  
Golpar Golmohammadzadeh ◽  
Abbas Mohammadpour ◽  
Nematollah Ahangar ◽  
Mohammad Shokrzadeh
Keyword(s):  
Breast Cancer ◽  
Case Control Study ◽  
Control Group ◽  
Fisher Exact Test ◽  
Mazandaran Province ◽  
Chi Square ◽  
Exact Test ◽  
Cyp1b1 Gene ◽  
Increased Risk ◽  
Control Study

BACKGROUND: The second leading cause of cancer-related death in women is breast cancer. Xenobiotic Metabolizing Enzymes (XMEs) contribute to the detoxification of numerous cancer therapy-induced products. In the metabolism of xenobiotic, cytochrome P450s or monooxygenases perform an important function by catalysing the hydroxylation reaction. In this study, the susceptibility and genetic polymorphisms of CYP450 isoenzymes was investigated that may have an etiological role in breast cancer. AIM: The main purpose of this study was to evaluate the association of CYP1A1 (rs4646421), CYP1B1 (rs1056836), CYP2C8 (rs1058930), and CYP19A1 (rs749292) polymorphisms with the risk of breast cancer in Mazandaran province. MATERIAL AND METHODS: This cross-sectional case-control study were recruited 72 patients and 51 healthy individuals and was performed between March 2018 to May 2018 in the Oncology Department at Imam Hospital in Sari city, Iran. Peripheral blood samples were collected in EDTA tube, and DNA extraction was performed using the salting-out method and WizPrep extraction kits. Breast cancer patients with known clinicopathological characters and healthy women as control group were genotyped for genes polymorphisms by PCR-RFLP technique, using restriction enzymes. Chi-square, Fisher exact test and Logistic regression model, were applied for statistical analysis. RESULTS: The results of the experiments showed that there was a significant relationship between two groups and the age of the patients is significantly higher than the control group (p = 0.044). According to the chi-square and Fisher exact test, education, pregnancy, menopause status and oppose were significant between the two groups. Based on using a logistic regression model in two normalized and age-adjusted models to finding relationship between the genotypes of each gene and breast cancer risk, it was determined that in the CYP2C8 genotype, those who have the CG allele have a 7.74 degree increased risk of breast cancer (CI = 95% 0.95-62.5) and in the CYP19A1 gene, individuals with GA genotype, increased risk of breast cancer (CI = %95 1.52-27.21), about the CYP1B1 gene, people with two genotypes of CG + GG had higher risk of breast cancer (CI = %95 1.19-5.71) and allele G has decreased risk of breast cancer in this gene (P = 0.0271), also allele G in CYP2C8 gene had the protective effect (P = 0.02). In the age-adjusted model, for the CYP2C8 gene, GG genotype increased risk of breast cancer (CI = %95 1.11-75.84) as well as, the CG + GG genotype in CYP1B1 gene (CI = %95 1.31-6.57). CONCLUSION: Our results confirm the association between CYP2C8 (rs1058930), CYP19A1 (rs749292) and CYP1B1 (rs1056836) gene polymorphisms and increased risk of breast cancer in women in Mazandaran province.

scholarly journals Comparison of Hospitalized Patients with Severe Pneumonia Caused by COVID-19 and Highly Pathogenic Avian Influenza (H7N9): A Retrospective Study from A Designated Hospital

2020 ◽  
Author(s):  
Binbin Gu ◽  
Lin Yao ◽  
XinYun Zhu ◽  
Pei-jun Tang ◽  
Cheng Chen
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Logistic Regression Analysis ◽  
Multiple Logistic Regression Analysis ◽  
Severe Pneumonia ◽  
Multivariable Logistic Regression Analysis ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Viral Shedding ◽  
Medical Supplies

Abstract Background Considerable attention has been focused on clinical features of Coronavirus Disease 2019 (COVID-19), it is also important for clinicians to differentiate it from influenza virus infections. Methods The clinical data of 23 cases of H7N9 and 23 cases of COVID-19 with severe pneumonia were collected. The comparisons were performed with the t test, Mann-Whitney U test, Fisher exact test or the chi-squared test, and multivariable logistic regression analysis. Results All of the cases were under the circumstance of sufficient medical staff and medical supplies. The rate of coexisting disease was lower in the severe COVID-19 group than in the severe H7N9 group (p < 0.05). Radiologically, severe COVID-19 patients had less consolidation and pleural effusion, but more crazy-paving pattern than severe H7N9 patients (p < 0.05). Clinically, compared to severe H7N9, severe COVID-19 patients were more inclined to surfer to relative better disease severity score, less secondary bacterial infection, a shorter time to beginning absorption on CT, but a longer duration of viral shedding from the admission (p < 0.05). Although more severe H7N9 patients needed non-invasive respiratory support, these two groups ultimately yielded comparable mortality. Based on multiple logistic regression analysis, severe COVID-19 infection was associated with a lower risk of the presence of severe ARDS (OR 0.964, 95% [CI] 0.931–0.998, p = 0.040), but exhibited longer duration of viral shedding (OR 0.734, 95% [CI] 0.550–0.980, p = 0.036) than severe H7N9 infection. Conclusion Although the conditions of severe H7N9 patients seemed to be more critical than those of severe COVID-19 patients, the relatively lower mortality of these two severe cases is to be expected in context of sufficient medical supplies.

Predictive factors for canine position in patients with unilateral cleft lip and palate

2020 ◽  
Author(s):  
Sara Rizell ◽  
Zahra Alhakim ◽  
Hans Mark ◽  
Julia Naoumova
Keyword(s):  
Regression Analysis ◽  
Predictive Factors ◽  
Bone Grafting ◽  
Medical Records ◽  
Hard Palate ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Exact Test ◽  
Multiple Stepwise Regression Analysis ◽  
Surgical Exposure

Summary Objectives The aims were to compare cleft and non-cleft canine position, to find predictive factors for canine position and to assess surgically exposed canines. Materials/Methods One hundred forty-eight individuals, born 1978–2005, with total unilateral cleft lip and palate (including Simonart’s band &lt;5 mm) treated in Gothenburg, were included. Canine angulation as well as vertical and horizontal position were assessed on panoramic radiographs (PAN) taken at the age of 10. Plausible predictive factors were registered from PAN, cast models and medical records. Data on spontaneous eruption or surgical exposure were available for 88 patients. Cleft- and non-cleft side was compared using paired t-test and Fisher’s exact test. Multiple stepwise regression analysis and logistic regression analysis were used to detect possible predictors for cleft canine position. Results The cleft canine angulation was 29.3 ± 13.1 degrees (mean ± standard deviation) versus 7.6 ± 8.2 degrees on the non-cleft side (p &lt; 0.001). Cleft canines were higher positioned and located closer to the midline compared to non-cleft canines (p &lt; 0.001). Age for both hard palate closure and bone grafting, cleft lateral agenesis as well as transposition were associated with canine position. Cleft canines that required surgical exposure (28%) had an increased angulation and were higher positioned than spontaneously erupted canines (p &lt; 0.001). Limitations The shortcomings were the retrospective design and incomplete assessment of the buccal–palatal canine position on 2D images. Conclusions/Implications With increased age for bone grafting, decreased age for hard palate closure and transposition, an association with abnormal canine position was found. A rigorous monitoring of cleft canine eruption is, therefore, advocated.

Improving Ambulatory Health Care Proxy Completion Rates: Implementing an Interdisciplinary Clinic-Based Process

2020 ◽  
Vol 35 (6) ◽  
pp. 491-499
Author(s):  
Lauge Sokol-Hessner ◽  
Griffen Allen ◽  
Jennifer Cluett
Keyword(s):  
Primary Care ◽  
Health Care ◽  
Care Practice ◽  
Fisher Exact Test ◽  
Health Care Proxy ◽  
Exact Test ◽  
The North ◽  
Increased Risk ◽  
Physician Leaders ◽  
Interdisciplinary Process

All adults should complete a health care proxy (HCP), especially those who are seriously ill or otherwise at increased risk of losing capacity. This study describes the implementation of an interdisciplinary process for helping patients complete HCPs during nonurgent visits at a large urban academic primary care practice between July 2014 and May 2017. The process was mapped using direct observations. Pre- and post-implementation measurement of the percent of patients who completed HCPs during their visit revealed significant improvement (1.4% vs 26.1% in the North Suite, special cause variation). Over the study period, the percentage of patients with HCP information rose significantly across the entire clinic (eg, 37% to 80% in the North Suite, Fisher exact test P < .0001; similar findings in other suites). Key facilitators and barriers to implementation were identified by physician leaders. An interdisciplinary process can sustainably improve the percentage of primary care patients with a completed HCP.

Epidermal growth factor receptor expression correlates with histologic grade but not microsatellite instability in primary colon carcinomas

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20023-20023
Author(s):  
R. L. Rego ◽  
A. J. French ◽  
N. R. Foster ◽  
D. J. Sargent ◽  
S. R. Alberts ◽  
...  
Keyword(s):  
Overall Survival ◽  
Microsatellite Instability ◽  
Disease Free Survival ◽  
Receptor Expression ◽  
High Dose ◽  
Colon Cancers ◽  
Egfr Expression ◽  
Primary Colon ◽  
Weighted Score ◽  
Clinicopathological Variables

20023 Background: EGFR is a transmembrane receptor tyrosine kinase belonging to the ErbB family of proteins. Anti-EGFR antibodies have shown efficacy as monotherapy and can enhance cytotoxic chemotherapy in patients with advanced colorectal cancers. We studied EGFR expression in primary colon cancers and its association with, microsatellite instability (MSI), clinicopathological variables and patient survival rates. Methods: Archival colon carcinomas were studied from patients with high risk Dukes’ stage B2 (n = 78) and C (n = 230) patients enrolled in a prior adjuvant trial of 5-fluorouracil, leucovorin plus standard dose or high-dose levamisole (NCCTG 91–46–53). EGFR expression (anti-EGFR H11 antibody, DAKO) was analyzed by immunohistochemistry (IHC) and intensity (0–3+), extent and their product (weighted score) were determined. MSI was analyzed using BAT26 and expression of hMLH1, hMSH2 and hMSH6 proteins by IHC. Patients were censored at 5 years after randomization for DFS and censored at 8 years post study randomization for overall survival (OS) data. Results: EGFR protein expression was detected in 216 of 308 (70%) of Dukes’ B2 and C primary colon carcinomas from patients and localized to the plasma membrane. EGFR expression variables (intensity, extent, weighted score) were increased in poor/undifferentiated compared to moderate/well differentiated tumors (p ≤ 0.036). Similar EGFR expression levels were found in MSI-H (n = 27) versus MSS (n = 203) colon cancers and for other clinicopathological variables. EGFR intensity was more likely moderate (2+) or strong (3+) in Dukes’ C versus B2 tumors (p = 0.088). In addition, higher EGFR intensity (2+, 3+) showed a trend toward worse disease-free survival (5 yr DFS %: 62.2 vs. 71.7; p = 0.095), but not overall survival (p = 0.14). Conclusions: EGFR overexpression is associated with increased tumor aggressiveness as indicated by poor tumor cell differentiation and reduced DFS in colon cancer patients receiving adjuvant 5-FU and levamisole. These findings indicate that EGFR may be an important therapeutic target in the adjuvant setting. [Table: see text]

Abstract 537: Higher Prevalence of Risk Alleles for Hyperuricemia Parallels Elevated Incidence of Gout and Growing Risk for Cardiovascular Diseases in a Hmong Population

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Youssef M Roman ◽  
Jenny D Xiong ◽  
Jeremiah S Menk ◽  
Kathleen Culhane-Pera ◽  
Robert J Straka
Keyword(s):  
Elevated Serum ◽  
Asian Population ◽  
Allele Frequencies ◽  
Fisher Exact Test ◽  
Snp Analysis ◽  
Cvd Risk ◽  
Significance Level ◽  
Exact Test ◽  
Risk Alleles ◽  
Increased Risk

Introduction: Hyperuricemia (HU) is the strongest predictor of gout and highly associated with major CVD including hypertension, HF, and CKD. The Hmong, a unique Asian population numbering > 60,000 in Minnesota, have a two-fold increased risk of gout compared to non-Hmong, rising prevalence of CVD, and may differ from other Asian populations in these regards. A genetic predisposition to elevated Serum Uric Acid (SUA) may help identify individuals at risk for gout and CVD. We quantified the Minor Allele Frequencies (MAFs) of known genetic variants (SNPs) associated with HU and compared the MAFs between our Hmong sample and both a reference (HapMap) population of Caucasian (CEU) as well as Han-Chinese (CHB). Methods: Salivary DNA from 235 self-identified Hmong was genotyped using either a Sequenom (iPLEX Gold) or TaqMan approach. MAFs for seven SNPs within candidate genes ( SLC2A9, SLC22A12, PDZK1, and ABCG2 ) identified by GWAS, were determined in our Hmong sample. Associations between HU and genotype were examined for 57/235 Hmong with known SUA levels. A Chi-Square or Fisher exact test with a Bonferroni corrected significance level (<0.007) was used to evaluate MAF differences. Mean SUA concentrations were compared by genotype using one-way ANOVA. Results: Our Hmong participant's age [mean (±SD)] was 30.2 (15.4) years, with >61% overweight or obese and a mean (±SD) SUA of 6.3 (1.7) mg/dL. Although the frequency of risk alleles in the Hmong were significantly higher compared to CEU (6/7) and CHB (3/7) populations, independent SNP by SNP analysis did not show a clear association with SUA. Risk allele frequencies were always more frequent in the Hmong versus comparator groups. Conclusion: MAFs of selected SNPs for HU are not independent of race. The higher prevalence of risk alleles for HU in the Hmong versus CEU and CHB populations may partly explain the clinically observed higher prevalence of gout and CVD risk in the Hmong. Although sample size precludes a robust assessment of an association between genotype and SUA, to our knowledge this is the first study to examine the genetic basis of HU in the Hmong.

scholarly journals Increased rate of venous thrombosis may be associated with inpatient dihydroergotamine treatment

Neurology ◽  
2017 ◽  
Vol 89 (3) ◽  
pp. 279-283 ◽  
Author(s):  
Amy R. Tso ◽  
Irene R. Patniyot ◽  
Amy A. Gelfand ◽  
Peter J. Goadsby
Keyword(s):  
Venous Thrombosis ◽  
San Francisco ◽  
Thrombotic Event ◽  
Anticoagulation Therapy ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Increased Risk ◽  
Treatment Dose ◽  
Low Threshold ◽  
The University

Objective:To review whether the incidence of catheter-associated venous thromboses was higher in patients receiving IV dihydroergotamine compared to lidocaine.Methods:We retrospectively reviewed all admissions at the University of California, San Francisco Headache Center from February 25, 2008, through October 31, 2014, for age, sex, diagnosis, aura, treatment dose, type of IV line used, days with line, superficial (SVT) or deep venous thrombosis (DVT), and pulmonary embolism (PE).Results:A peripherally inserted central catheter (PICC) or midline catheter was placed in 315 of 589 (53%) admissions. Mean age was 38 years with a range of 6 to 79 years; 121 patients (21%) were ≤18 years old. Seventy-four percent (433 of 589) of patients were female. Of 263 dihydroergotamine admissions using a PICC or midline catheter, 19 (7.2%) had either an SVT or DVT or a PE; 2 patients were diagnosed with both DVT and PE. Of 52 lidocaine admissions using a PICC or midline catheter, none had a thrombotic event (p = 0.05, Fisher exact test). Age, sex, aura, total dihydroergotamine dose, and number of days with line were not significant predictors of venous thrombosis.Conclusions:IV dihydroergotamine treatment may be associated with an increased risk of catheter-associated venous thrombosis. A low threshold for diagnostic ultrasound investigation is appropriate because anticoagulation therapy was frequently required.

Microsatellite instability but not thymidylate synthase is a prognostic variable in primary colon cancers from patients treated in 5-FU-based adjuvant studies

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10019-10019
Author(s):  
F. A. Sinicrope ◽  
R. L. Rego ◽  
K. C. Halling ◽  
N. R. Foster ◽  
D. J. Sargent ◽  
...  
Keyword(s):  
Overall Survival ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Thymidylate Synthase ◽  
Dna Mismatch Repair ◽  
Histologic Grade ◽  
Dna Mismatch ◽  
Colon Cancers ◽  
Lower Stage ◽  
Primary Colon

10019 Background: Colon cancers with microsatellite instability (MSI) display resistance to 5-fluorouracil (5-FU), and in vitro resistance can be reversed by restoring DNA mismatch repair proficiency. 5-FU inhibits the thymidylate synthase (TS) enzyme and TS may predict clinical outcome after 5-FU-based chemotherapy. To define molecular predictors of prognosis, we analyzed TS, p53, chromosome 17p allelic imbalance (AI), and patient survival stratified by MSI status. Methods: Primary colon carcinomas from patients enrolled in five 5-FU-based adjuvant therapy trials were analyzed for MSI and 17p AI using 11 microsatellite markers (MSI-H: ≥ 30% of the loci demonstrating instability). For 17p AI, markers included D17S261 and TP53 at or near the p53 locus. Expression of DNA mismatch repair (hMLH1, PharMingen; hMSH2; Oncogene), TS (TS106, Zymed), and p53 (D07, Novacastra) proteins were analyzed by immunohistochemistry. Correlations between markers and associations with overall survival (OS) were determined. Patients were censored at 5 years for DFS and at 8 years post study randomization for overall survival (OS) data. Results: Of 320 Dukes’ stage B2 and C cancers studied, 60 of 320 (19%) were MSI-H. TS expression variables (intensity, extent, weighted score) were similar in MSI-H and MSI stable/low frequency (MSS/MSI-L) cancers; similar results were found using DNA mismatch repair (dMMR) proteins. MSI-H tumors had lower stage (p= 0.0007), fewer metastatic lymph nodes (p= 0.004), and improved OS (vs. MSS/MSI-L tumors; p= 0.01). Loss of dMMR proteins was also associated with better OS (p= 0.006). None of the TS variables were prognostic for OS. Histologic grade (p= 0.0008) and nodal status (p= 0.0002) were associated with OS in contrast to 17p LOH or p53. Only MSI status or dMMR, histologic grade, and tumor stage were independent markers for OS. Conclusions: MSI-H tumors show earlier stage at presentation and better stage-adjusted survival rates. MSI status and TS expression were unrelated and TS was not prognostic, suggesting that TS levels cannot explain therapeutic resistance to 5-FU reported in MSI-H colon cancers. [Table: see text]

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