Microsatellite instability in colorectal cancer: An analysis of the National Cancer Database.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 134-134
Author(s):  
Kamelah Abushalha ◽  
Sawsan Abulaimoun ◽  
Sarah J Aurit ◽  
Erin Jenkins ◽  
Peter T. Silberstein
Keyword(s):  
Colorectal Cancer ◽  
Regression Model ◽  
Microsatellite Instability ◽  
Mucinous Adenocarcinoma ◽  
Medullary Carcinoma ◽  
Left Colon ◽  
Right Colon ◽  
White Race ◽  
Factors Associated ◽  
Colon And Rectum

134 Background: High-frequency microsatellite instability (MSI-H) accounts for roughly 15% of all cases of colorectal cancer (CRC). Studies suggest a significant non-adherence to routine MSI testing in patients diagnosed with CRC despite universal guidelines. Methods: We used the NCDB to identify adults with MSI-H status CRC from 2010-2015 with the following histologic subtypes: mucinous and not otherwise specified adenocarcinoma, and medullary carcinoma. The primary site was localized to the right colon, left colon, and rectum; demographic factors, clinicopathologic features, and treatments were identified. Patients were stratified by site and discrete and continuous variable comparisons were made using the chi-square and Mann-Whitney test, respectively. Survival was examined with the Kaplan-Meier method and a Cox proportional hazards regression model. A logistic regression model was used to examine MSI status. All analyses were conducted with SAS version 9.4. Results: A total of 5364 patients were identified and stratified by site into 3 groups: right colon (n = 4004, 74.6%), left colon (n = 890, 16.59%) and rectum (n = 470, 8.76%). Compared to the left colon and rectum, right colon patients were more likely to be older females with larger tumors and less likely to receive chemoradiation. After adjusting for all else, we found statistical evidence that female vs. male gender (OR = 1.47; 95% CI: 1.24 to 1.73), Black vs. White race (OR = 0.61; 0.45 to 0.83), left vs. right colon (OR = 0.33, 0.27 to 0.41), rectum vs. right colon (OR = 0.08, 0.05 to 0.13), mucinous adenocarcinoma vs. adenocarcinoma (OR = 2.37, 1.92 to 2.93), medullary carcinoma vs. adenocarcinoma (OR = 8.86, 4.56 to 17.22), positive vs. negative k-RAS mutation (OR = 0.49, 0.41 to 0.59), and positive vs. negative CEA status (OR = 0.79, 0.66 to 0.94) were factors associated with MSI-H status. Improved survival was associated were Hispanic white race, stage 1, and free surgical margins within a multivariable context. Factors associated with poor survival: increased Charlson/Deyo score, advanced stage, lymphovascular invasion, and positive CEA status. Conclusions: In settings where resources are scarce and universal testing is not possible, there is a benefit from MSI testing in female patients, those with right-sided colon cancer, mucinous adenocarcinoma, and medullary carcinoma.

Oncogenic mutations in colorectal cancer, indications for anatomical sites, and targeted intervention.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22037-e22037
Author(s):  
Giovanni Corso ◽  
Valeria Pascale ◽  
Giuseppe Flauti ◽  
Daniele Marrelli ◽  
Franco Roviello
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Microsatellite Instability ◽  
Cancer Patients ◽  
Left Colon ◽  
Targeted Intervention ◽  
Right Colon ◽  
Right Colon Cancer ◽  
Oncogenic Mutations ◽  
Colorectal Cancer Patients

e22037 Background: Oncogenic mutations, such as KRAS, in colorectal cancer patients are considered standard molecular biomarkers that predict the clinical benefit for the targeted intervention with EGFR inhibitors. In addition, these mutations are associated with specific anatomical area in the colon tumor development, as BRAF mutations with the microsatellite instability. Methods: In this translational study we aim to assess the mutation frequencies of the EGFR [hotspot area and polyadenine deletions (A13_del)], KRAS, BRAFV600E, and PIK3CA oncogenes in a series of 280 colorectal cancer patients. Microsatellite instability phenotype is considered in this series. All patients' clinicopathological data were considered for statistical analysis and associations. Results: In this study, we verified multiple associations between oncogenic mutations and specified clinicopathological tumor features. Respectively, we identified the following significant results: 1) EGFR A13_deletions are associated with right colon carcinoma (22.2% vs. 3.3%; p<0.005), mucinous histotype (16% vs. 7.8%; p=0.042), G3 grading (19% vs. 7.3%; p=0.024) and microsatellite instability status (p<0.005); 2) PIK3CA mutations are related mucinous histotype (12% vs. 4.4%; p=0.021) 3) KRASG12 and KRASG13mutations are correlated respectively with the left (91.4% vs. 59.3%) and right (40.7% vs. 8.6%) colon cancer development (p<0.005), and finally 4) microsatellite instability is associated with right colon tumors (28.4% vs. 5.5%; p<0.005). Conclusions: Mostly, we verified a high frequency rate of the KRASG13 and EGFR A13_del oncogene mutations in right colon cancer; whereas KRASG12 codon mutation occurs more frequently in left colon cancers. In particular, we assessed that right colon cancer is associated with specific molecular characteristics, in comparison to left colon tumors. These evidences, in association with specific clinicopathological data, can delineate novel approaches for the colorectal cancer classification and targeted intervention.

The correlation between mismatch repair status and clinicopathological characteristics in Chinese colorectal cancer patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 544-544 ◽  
Author(s):  
Zhi-tao Xiao ◽  
Rong-xin Zhang ◽  
Yang Zhao ◽  
Jian-Hong Peng ◽  
Pei-Rong Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Mismatch Repair ◽  
Mucinous Adenocarcinoma ◽  
Clinicopathological Characteristics ◽  
Left Colon ◽  
Stage Ii ◽  
Chinese Patients ◽  
Right Colon ◽  
Significant Difference

544 Background: Our study aimed to explore the relationship between mismatch repair (MMR) status and clinicopathological characteristics in Chinese patients with colorectal cancer (CRC). Methods: A total of 2684 patients with histologically confirmed adenocarcinoma of CRC were consecutively recruited between May 2011 and May 2015 at Sun Yat-sen University cancer center. The exclusion criteria included multiple primary tumors, synchronous and metachronous CRC, and familial adenomatous polyposis. The CRC was defined as left colon with the tumor located below the splenic flexure or rectum, otherwise grouped as right colon. Correlations of MMR status and patient’s demographics, tumor characteristics and TNM staging (exclude 315 CRC patients receiving neoadjuvant therapy) were investigated. Results: We found that deficient MMR (dMMR) status was more likely detected in younger CRC patients compared to the the elderly (12.7% vs 7.5%, P < 0.001). The dMMR rate in right colon cancer was significantly higher than that in left colon cancer and rectal cancer (22.7% vs 7.2% vs 5.2%, P < 0.001).With respect to tumor differentiation, we found that the mucinous adenocarcinoma had the highest rate of dMMR(24.4%), followed by poorly differentiated adenocarcinoma(18.5%), signet-ring cell carcinoma(17.6%), well differentiated adenocarcinoma(9.5%), moderately differentiated adenocarcinoma(8.9%), and neuroendocrine carcinoma (0%) ( P < 0.001). In addition, the proportions in stage I, stage II, stage III and stage IV CRC were 9.7%, 16.5% , 8.5% and 3.9%, respectively ( P < 0.001). There was no significant difference in gender (P = 0.114). Conclusions: At the first time, our study demonstrated that dMMR status was most likely detected at younger age (less than 59 years) and stage II right colon mucinous adenocarcinoma in large volume Chinese patients, which was similar to the results in western countries.

scholarly journals PD-L1 Expression Patterns in Microsatellite Instability-High Intestinal Adenocarcinoma Subtypes

2019 ◽  
Vol 152 (3) ◽  
pp. 384-391 ◽  
Author(s):  
Jordan Roberts ◽  
Safia N Salaria ◽  
Justin Cates ◽  
Yang Wang ◽  
Cindy Vnencak-Jones ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Tumor Cells ◽  
Mucinous Adenocarcinoma ◽  
Expression Patterns ◽  
Inflammatory Cells ◽  
Medullary Carcinoma ◽  
Molecular Features ◽  
Programmed Death ◽  
Programmed Death Protein 1 ◽  
Histologic Subtypes

Abstract Objectives To investigate patterns of programmed death protein-1 (PD-L1) expression in microsatellite instability (MSI)-high intestinal carcinomas and correlate them with pathologic and molecular features. Methods One hundred and fifteen MSI-high and 41 microsatellite stable carcinomas were included. Tumor sections were immunohistochemically labeled for PD-L1. The results were correlated with histologic subtypes, MSI, and BRAF status. Results As expected, MSI status was associated with PD-L1 expression. Among 115 MSI-high tumors, PD-L1 expression was observed on tumor cells in 28 tumors and on tumor-associated inflammatory cells in 77 tumors. Medullary carcinoma demonstrated more frequent PD-L1 expression on tumor cells than mucinous and typical adenocarcinoma. PD-L1 expression was more frequent in medullary and typical adenocarcinoma than in mucinous adenocarcinoma based on combined positive scores. Tumors with more nucleotide shifts by PCR-based MSI testing were more likely to express PD-L1. Conclusions Expression of PD-L1 is different among different histologic subtypes of MSI-high intestinal carcinomas.

Metastatic pattern and tumor sidedness in colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15147-e15147
Author(s):  
Mahvish Muzaffar ◽  
Abdul Rafeh Naqash ◽  
Darla K. Liles ◽  
Sumyra Kachru
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Regression Model ◽  
Predictive Factor ◽  
Primary Tumor ◽  
Left Colon ◽  
Cancer Site ◽  
Metastatic Colon Cancer ◽  
Metastatic Pattern ◽  
Left Colon Cancer

e15147 Background: Tumor side has emerged as an important prognostic and predictive factor in metastatic colon cancer. We sought to study its impact on the metastatic pattern of colorectal cancer. Methods: The SEER database (version 8.3.5) was reviewed for patients with Stage IV colorectal cancer diagnosed between 2004-2015. We only included patients with labeled primary site, and excluded appendiceal, unlabeled and autopsy alone cases. Variables included in the analysis were: age, race, gender, grade, primary tumor side and sites of metastasis at diagnosis. Primary outcome analyzed was overall survival and disease specific survival.Cox proportional hazard regression model was employed to test the association between survival and side of cancer/ site of metastasis. Results: A total of 74,768 cases were identified who met the eligibility criteria. The mean age was 68.5 yrs. for right colon cancer (RCC),64.0 yrs. for left colon cancer (LCC). and 62.9 yrs. for rectal cancer. White race was predominant group for RCC, LCC and rectum. More females were vs men in RCC (52% vs 48%), LCC (44% vs 56%) and rectum (60% vs 40%). (The cox regression model suggested inferior outcome for black race HR 1.05(1.03-1.07) (<0.001), high grade HR 1.32(1.30-1.35) p<.0001, right side tumors HR 1.23(1.21-1.250, p <.0001 (table). Conclusions: Over last few years tumor sidedness has emerged as an important prognostic and predictive factor in colon cancer. Our study also highlights the impact of sidedness on survival irrespective of distant metastatic pattern. This analysis contributes to the ongoing discussion that right and left colon cancer are two distinct disease entities. Impact of primary tumor side and metastatic site on survival in colorectal cancer. [Table: see text]

Value of Mismatch Repair, KRAS, and BRAF Mutations in Predicting Recurrence and Benefits From Chemotherapy in Colorectal Cancer

2011 ◽  
Vol 29 (10) ◽  
pp. 1261-1270 ◽  
Author(s):  
Gordon Hutchins ◽  
Katie Southward ◽  
Kelly Handley ◽  
Laura Magill ◽  
Claire Beaumont ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Mutational Analysis ◽  
Left Colon ◽  
Rectal Tumors ◽  
Wild Type ◽  
Right Colon ◽  
Kras Mutations ◽  
Risk Of Recurrence ◽  
Braf Mutant

Purpose It is uncertain whether modest benefits from adjuvant chemotherapy in stage II colorectal cancer justify the toxicity, cost, and inconvenience. We investigated the usefulness of defective mismatch repair (dMMR), BRAF, and KRAS mutations in predicting tumor recurrence and sensitivity to chemotherapy. Patients and Methods Immunohistochemistry for dMMR and pyrosequencing for KRAS/BRAF were performed for 1,913 patients randomly assigned between fluorouracil and folinic acid chemotherapy and no chemotherapy in the Quick and Simple and Reliable (QUASAR) trial. Results Twenty-six percent of 695 right-sided colon, 3% of 685 left-sided colon, and 1% of 407 rectal tumors were dMMR. Similarly, 17% of right colon, 2% of left colon, and 2% of rectal tumors were BRAF mutant. KRAS mutant tumors were more evenly distributed: 40% right colon, 28% left colon, and 36% rectal tumors. Recurrence rate for dMMR tumors was half that for MMR-proficient tumors (11% [25 of 218] v 26% [438 of 1,695] recurred; risk ratio [RR], 0.53; 95% CI, 0.40 to 0.70; P < .001). Risk of recurrence was also significantly higher for KRAS mutant than KRAS wild-type tumors (28% [150 of 542] v 21% [219 of 1,041]; RR, 1.40; 95% CI, 1.12 to 1.74; P = .002) but did not differ significantly between BRAF mutant and wild-type tumors (P = .36). No marker predicted benefit from chemotherapy with efficacy not differing significantly by MMR, KRAS, or BRAF status. The prognostic value of MMR and KRAS was similar in the presence and absence of chemotherapy. Conclusion MMR assays identify patients with a low risk of recurrence. KRAS mutational analysis provides useful additional risk stratification to guide use of chemotherapy.

scholarly journals Clinical presentations of colorectal cancer at initial presentation to hospital and its site specific correlation

2018 ◽  
Vol 6 (11) ◽  
pp. 3652
Author(s):  
Rauf Ahmad Bhat ◽  
Shams Ul Bari
Keyword(s):  
Colorectal Cancer ◽  
Hepatic Flexure ◽  
Left Colon ◽  
Age Group ◽  
Right Colon ◽  
Site Specific ◽  
Clinical Presentations ◽  
Number Of Patients ◽  
Bleeding Per Rectum ◽  
Sixth Decade

Background: Colorectal cancer is one of the leading cause of death all over the world. It progresses slowly and may be asymptomatic for as many as 5 years. Aim of this study was to find the incidence and the initial clinical presentations of patients with colorectal cancer and its site specific correlationMethods: This was a prospective hospital-based study conducted over a period of two years from August 2015 to September 2017 in the postgraduate department of surgery, Government medical college, Srinagar. Total of fifty three patients in the age group of 10 years to 80 years were included in the study. Colorectal tumors were divided into right colon growths (caecum, ascending colon and hepatic flexure), left colon growths (splenic flexure, descending colon and sigmoid colon) and rectal growths. Data was collected from their hospital records and analysed using SPSS computer program.Results: In present study incidence of colorectal cancer was 0.2 per 100,000 people. Thirty percent of our patients were found to be in the sixth decade of their life with male preponderance in almost every age group. Mean age of presentation being 46.44 years (males= 48.5years, females= 43.76years). Out of 53 patients, rectal growths constituted 36%, left colonic growths 36% followed by 28% cases of right colonic growths. More than one symptom was present in several patients. Maximum number of patients (43%) presented with anemia (microcytic hypochromic) with Hb of <9gm% followed by constipation 38% and bleeding per rectum 28%. Pain abdomen was present in 23% of patients. Loss of weight and diarrhoea was equally seen in 19% of patients. Diarrhoea was seen in 6 males and 4 females and was statistically significant (p<0.05).Conclusions: Colorectal cancer was found to affect the Kashmiri patients at younger age (38% were 40 years or less) with peak incidence at sixth decade. Males were affected more than females. Anaemia, constipation and bleeding per rectum were the most common predominant clinical features in right colon, left colon and rectal growths respectively.

Hurdle Poisson Regression Model for Identifying Factors Related to Noncompliance and Waiting Time for Confirmatory Diagnosis in Colorectal Cancer Screening

2019 ◽  
Vol 35 (2) ◽  
pp. 85-91 ◽  
Author(s):  
Hsiao-Hsuan Jen ◽  
Tsung-Hsi Wang ◽  
Han-Mo Chiu ◽  
Szu-Min Peng ◽  
Chen-Yang Hsu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Regression Model ◽  
Waiting Time ◽  
Poisson Regression ◽  
Contextual Factors ◽  
Individual Characteristics ◽  
Assessment Model ◽  
Poisson Regression Model ◽  
Screening Programs ◽  
Factors Associated

AbstractObjectivesPopulation-based colorectal cancer (CRC) screening programs that use a fecal immunochemical test (FIT) are often faced with a noncompliance issue and its subsequent waiting time (WT) for those FIT positives complying with confirmatory diagnosis. We aimed to identify factors associated with both of the correlated problems in the same model.MethodsA total of 294,469 subjects, either with positive FIT test results or having a family history, collected from 2004 to 2013 were enrolled for analysis. We applied a hurdle Poisson regression model to accommodate the hurdle of compliance and also its related WT for undergoing colonoscopy while assessing factors responsible for the mixture of the two outcomes.ResultsThe effect on compliance and WT varied with contextual factors, such as geographic areas, type of screening units, and level of urbanization. The hurdle score, representing the risk score in association with noncompliance, and the WT score, reflecting the rate of taking colonoscopy, were used to classify subjects into each of three groups representing the degree of compliance and the level of health awareness.ConclusionOur model was not only successfully applied to evaluating factors associated with the compliance and the WT distribution, but also developed into a useful assessment model for stratifying the risk and predicting whether and when screenees comply with the procedure of receiving confirmatory diagnosis given contextual factors and individual characteristics.

scholarly journals Effectiveness of screening colonoscopy in reducing the risk of death from right and left colon cancer: a large community-based study

Gut ◽  
2016 ◽  
Vol 67 (2) ◽  
pp. 291-298 ◽  
Author(s):  
Chyke A Doubeni ◽  
Douglas A Corley ◽  
Virginia P Quinn ◽  
Christopher D Jensen ◽  
Ann G Zauber ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mortality Risk ◽  
Left Colon ◽  
Screening Colonoscopy ◽  
Cancer Death ◽  
Right Colon ◽  
Community Based ◽  
Risk Of Death ◽  
Colon Cancers ◽  
Rectal Cancers

ObjectiveScreening colonoscopy's effectiveness in reducing colorectal cancer mortality risk in community populations is unclear, particularly for right-colon cancers, leading to recommendations against its use for screening in some countries. This study aimed to determine whether, among average-risk people, receipt of screening colonoscopy reduces the risk of dying from both right-colon and left-colon/rectal cancers.DesignWe conducted a nested case–control study with incidence-density matching in screening-eligible Kaiser Permanente members. Patients who were 55–90 years old on their colorectal cancer death date during 2006–2012 were matched on diagnosis (reference) date to controls on age, sex, health plan enrolment duration and geographical region. We excluded patients at increased colorectal cancer risk, or with prior colorectal cancer diagnosis or colectomy. The association between screening colonoscopy receipt in the 10-year period before the reference date and colorectal cancer death risk was evaluated while accounting for other screening exposures.ResultsWe analysed 1747 patients who died from colorectal cancer and 3460 colorectal cancer-free controls. Compared with no endoscopic screening, receipt of a screening colonoscopy was associated with a 67% reduction in the risk of death from any colorectal cancer (adjusted OR (aOR)=0.33, 95% CI 0.21 to 0.52). By cancer location, screening colonoscopy was associated with a 65% reduction in risk of death for right-colon cancers (aOR=0.35, CI 0.18 to 0.65) and a 75% reduction for left-colon/rectal cancers (aOR=0.25, CI 0.12 to 0.53).ConclusionsScreening colonoscopy was associated with a substantial and comparably decreased mortality risk for both right-sided and left-sided cancers within a large community-based population.

scholarly journals MUC5AChypomethylation is a predictor of microsatellite instability independently of clinical factors associated with colorectal cancer

2014 ◽  
Vol 136 (12) ◽  
pp. 2811-2821 ◽  
Author(s):  
Florence Renaud ◽  
Audrey Vincent ◽  
Christophe Mariette ◽  
Michel Crépin ◽  
Laurence Stechly ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Clinical Factors ◽  
Factors Associated

scholarly journals Smoking-Related Risks of Colorectal Cancer by Anatomical Subsite and Sex

2020 ◽  
Vol 189 (6) ◽  
pp. 543-553 ◽  
Author(s):  
Inger T Gram ◽  
Song-Yi Park ◽  
Lynne R Wilkens ◽  
Christopher A Haiman ◽  
Loïc Le Marchand
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Colon Cancer ◽  
Cox Regression ◽  
Left Colon ◽  
Right Colon ◽  
Right Colon Cancer ◽  
Increased Risk ◽  
The Right ◽  
Incident Cases

Abstract The purpose of this study was to examine whether the increased risk of colorectal cancer due to cigarette smoking differed by anatomical subsite or sex. We analyzed data from 188,052 participants aged 45–75 years (45% men) who were enrolled in the Multiethnic Cohort Study in 1993–1996. During a mean follow-up period of 16.7 years, we identified 4,879 incident cases of invasive colorectal adenocarcinoma. In multivariate Cox regression models, as compared with never smokers of the same sex, male ever smokers had a 39% higher risk (hazard ratio (HR) = 1.39, 95% confidence interval (CI): 1.16, 1.67) of cancer of the left (distal or descending) colon but not of the right (proximal or ascending) colon (HR = 1.03, 95% CI: 0.89, 1.18), while female ever smokers had a 20% higher risk (HR = 1.20, 95% CI: 1.06, 1.36) of cancer of the right colon but not of the left colon (HR = 0.96, 95% CI: 0.80, 1.15). Compared with male smokers, female smokers had a greater increase in risk of rectal cancer with number of pack-years of smoking (P for heterogeneity = 0.03). Our results suggest that male smokers are at increased risk of left colon cancer and female smokers are at increased risk of right colon cancer. Our study also suggests that females who smoke may have a higher risk of rectal cancer due to smoking than their male counterparts.

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