Clinical implications of microsatellite instability in mucinous colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 657-657
Author(s):  
Fergus Keane ◽  
Darrell Martin ◽  
Gregory D. Leonard ◽  
Sean Hynes ◽  
Margaret Sheehan
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Who Classification ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Stage Iii ◽  
Low Grade ◽  
Tumor Type ◽  
Response To Chemotherapy ◽  
Microsatellite Stability

657 Background: Colorectal Cancer(CRC) is becoming increasingly recognised as a heterogeneous tumor type. Mucinous histological subtype is identified in 10-15% of CRCs, most commonly those with microsatellite instability (MSI), and has traditionally been associated with unfavorable outcomes and poor response to chemotherapy. In contrast, MSI is associated with relatively favourable pathological features and better outcomes, compared with CRCs with microsatellite stability (MSS), such that under the 2010 WHO classification, MSI mucinous CRC is considered low grade, while MSS mucinous CRC is classified as high grade. The aim of this study is to establish the significance of microsatellite stability status in non-metastatic mucinous colorectal cancer. Methods: Between 2010 and 2017, 69 patients with stage II or stage III mucinous colorectal cancer were identified. Microsatellite status was tested in all patients (MSS or MSI), and histological and clinical data, as well as recurrence rates, were assessed in both groups. MSI status was established using polymerase chain reaction(PCR) technique. Results: Sixty-nine patients with mucinous CRC were identified. The median age for the entire group was 73 years (range 32-87), no difference in gender was identified. 63%(n=43) and 37%(n=26) were stage II and stage III respectively at diagnosis. The majority of mucinous CRCs were right-sided (72%). 33% (n=23) were identified as microsatellite unstable (MSI). MSI status was associated with right sided tumours (78% right-sided vs 22% left-sided, p<0.05), older age at diagnosis (mean 76 years vs 68 years, p=0.01), and lower TNM staging at diagnosis (83% vs 52% diagnosed stage 2, p=0.007) compared with the MSS group. A lower disease recurrence rate was identified in the MSI group (4.3% vs 13% in MSS group) at median follow-up time of 33 months (range 8-93 months). Conclusions: In patients with mucinous colorectal cancer, MSI status is a useful marker of favourable histological and clinical features, and is associated with better outcomes. Our study supports the current 2010 WHO classification, and highlights the clinical and prognostic significance of MSI status in this patient cohort.

scholarly journals Thrombocytosis portends adverse prognostic significance in patients with stage II colorectal carcinoma

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 180 ◽  
Author(s):  
Tianhua Guo ◽  
Marcin Krzystanek ◽  
Zoltan Szallasi ◽  
Arpad Szallasi
Keyword(s):  
Colorectal Cancer ◽  
Platelet Count ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Stage Iv ◽  
Early Recurrence ◽  
Stage Ii ◽  
Stage Iii ◽  
Normal Limits ◽  
Stage Ii Colon Cancer

Thrombocytosis portends adverse prognostic significance in many types of cancers including ovarian and lung carcinoma. In this study, we determined the prevalence and prognostic significance of thrombocytosis (defined as platelet count in excess of 400 × 103/μl) in patients with colorectal cancer. We performed a retrospective analysis of 310 consecutive patients diagnosed at our Institution between 2004 and 2013. The patients (48.7% male and 51.3% female) had a mean age of 69.9 years (+/- 12.7 years) at diagnosis. Thrombocytosis was found in a total of 25 patients, with a higher incidence in those with stage III and IV disease (14.4% of patients). Although the mean platelet count increased with the depth of tumor invasion (pT), its values remained within normal limits in the whole patient cohort. No patient with stage I cancer (n=57) had elevated platelet count at diagnosis. By contrast, five of the 78 patients (6.4%) with stage II cancer showed thrombocytosis, and four of these patients showed early recurrence and/or metastatic disease, resulting in shortened survival (they died within one year after surgery). The incidence of thrombocytosis increased to 12.2% and 20.6%, respectively, in patients with stage III and IV disease. The overall survival rate of patients with thrombocytosis was lower than those without thrombocytosis in the stage II and III disease groups, but this difference disappeared in patients with stage IV cancer who did poorly regardless of their platelet count. We concluded that thrombocytosis at diagnosis indicates adverse clinical outcome in colorectal cancer patients with stage II or III disease. This observation is especially intriguing in stage II patients because the clinical management of these patients is controversial. If our data are confirmed in larger studies, stage II colon cancer patients with thrombocytosis may be considered for adjuvant chemotherapy.

Prognostic significance of KRAS and BRAF mutations in Japanese patients with colorectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14033-e14033
Author(s):  
Eiji Oki ◽  
Ryota Nakanishi ◽  
Koji Ando ◽  
Hiroshi Saeki ◽  
Takefumi Ohga ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Braf Mutation ◽  
Kras Mutation ◽  
Molecular Mechanisms ◽  
Prognostic Significance ◽  
Japanese Patients ◽  
Genetic Alterations ◽  
Stage Ii ◽  
Anatomical Site

e14033 Background: Recent evidence highlights the potential prognostic and predictive value of BRAF and K-RAS gene alterations in patients with colorectal cancer. To determine whether differences exist in the molecular mechanisms driving colorectal cancer between Japanese and Western, we characterized Japanese patients with colorectal cancer by assessing genetic alterations involved in cancer progression and response to treatment. Methods: We retrospectively evaluated 254 Japanese diagnosed with colorectal cancer at our institution between 1994 and 2009. Mutations in KRAS codons 12 and 13 and BRAF codon 600 were identified by direct sequencing. Microsatellite instability (MSI) status was determined by genotyping in the 5 loci. Associations between KRAS or BRAF mutation and clinicopathological characteristics and prognosis were evaluated. Results: KRAS and BRAF mutation were detected in 33.5% and 6.7% of all patients, respectively. KRAS mutation was correlated with poor recurrence free survival (RFS) (p = 0.03), especially in stage II patients (p = 0.007). BRAF mutation was significantly correlated with the anatomical site of tumor (p < 0.001), tumor grade (p = 0.001) and high frequency of microsatellite instability (p < 0.001). BRAF mutation was also correlated with poor overall survival in all cases of patients (p = 0.009). Overall, the background of KRAS and BRAF mutation was almost similar between CRCs of Western countries and those of Japanese. However, KRAS mutation status was considered to be helpful to predict recurrence in Japanese patients with stage II CRC. Conclusions: Our findings indicate that BRAF and K-RAS mutation plays an important role in the tumorigenesis of colorectal cancer. These results indicate that molecular analysis for BRAF and K-RAS may be a useful biomarker for identifying patients with right-sided colon cancer with poor outcome who may benefit from a more individualized course of therapy.

Prognostic Significance of Microsatellite Instability and Ki-ras Mutation Type in Stage II Colorectal Cancer

Oncology ◽  
2003 ◽  
Vol 64 (3) ◽  
pp. 259-265 ◽  
Author(s):  
Cathy Wang ◽  
Marius van Rijnsoever ◽  
Fabienne Grieu ◽  
Sean Bydder ◽  
Hany Elsaleh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Stage Ii Colorectal Cancer ◽  
Mutation Type

Immunohistochemical Test for MLH1 and MSH2 Expression Predicts Clinical Outcome in Stage II and III Colorectal Cancer Patients

2006 ◽  
Vol 24 (15) ◽  
pp. 2359-2367 ◽  
Author(s):  
Giovanni Lanza ◽  
Roberta Gafà ◽  
Alessandra Santini ◽  
Iva Maestri ◽  
Laura Guerzoni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Stage Iii ◽  
Prognostic Information ◽  
Colorectal Cancer Patients ◽  
Risk Of Cancer

Purpose To evaluate the prognostic significance of DNA mismatch repair (MMR) status in a large series of stage II and III colorectal cancer patients. The relationship among MMR status, adjuvant chemotherapy, and clinical outcome was also investigated. Patients and Methods The study included 718 patients with colorectal adenocarcinoma (393 stage II and 325 stage III) who underwent curative surgical resection. MMR status was determined by immunohistochemical analysis of MLH1 and MSH2 expression. Microsatellite instability (MSI) was assessed in 363 patients using mononucleotide and dinucleotide markers. Results One hundred fourteen (15.9%) carcinomas showed abnormal MMR protein (MMRP) expression (96 MLH1 negative and 18 MSH2 negative) and were classified as MMRP negative, whereas 604 tumors demonstrated normal MLH1/MSH2 immunoreactivity (MMRP positive). MLH1/MSH2 expression was closely related to MSI status (P < .001) and several clinicopathologic features. Patients with MMRP-negative carcinomas demonstrated a marked reduction in the risk of cancer-related death with respect to patients with MMRP-positive tumors (hazard ratio, 0.2579; 95% CI, 0.1289 to 0.5159). A better clinical outcome for patients with MMRP-negative tumors was observed in both stage II (P = .0006) and stage III (P = .0052) disease. In stage III disease, the survival advantage conferred by MMRP-negative tumors was more evident among patients treated with surgery alone than among patients who received adjuvant chemotherapy. A nonsignificant trend for survival benefit from adjuvant chemotherapy was observed among patients with MMRP-positive carcinomas but not among those with MMRP-negative carcinomas. Conclusion Immunohistochemical testing for MLH1/MSH2 expression provides useful prognostic information for the management of stage II and III colorectal cancer patients.

scholarly journals Prognostic significance of macrosatellite instability in patients under 50 years of age suffering from colorectal cancer

2009 ◽  
Vol 62 (5-6) ◽  
pp. 217-223
Author(s):  
Atila Fenjvesi
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Prognostic Significance ◽  
Young Patients ◽  
Dna Mismatch ◽  
Significant Difference ◽  
Sporadic Cases ◽  
Microsatellite Stability ◽  
Better Than

Introduction Colorectal cancer (CRC) can arise through two distinct mutational pathways: microsatellite instability or chromosomal instability. High-frequency microsatellite instability (MSI) occurs in approximately 15 percent of sporadic cases of CRCs. Many studies have well established that MSI, the hallmark of defective DNA mismatch repair, is associated with prolonged survival of CRC patients compared with tumors that are microsatellite stable. CRCs in patients under 50 years of age are rare and represent about 5% of the total number of tumors. The aim of this study was to analyze the prognostic significance of MSI in CRC patients younger than 50 at the time of diagnosis. Material and methods 31 patients with CRC under 50 years of age were tested for the presence of MSI, and compared with 35 patients aged 50 or more at the time of diagnosis. CRC-specific survival five-year- follow-up period was analyzed in relation to MSI status. Results The frequency of MSI among the young patients was 35.48%, which was significantly higher than the rate of 11.43% noted in older patients with CRCs (p<0.042). This study revealed no difference in survival in patients with CRCs aged less than 50 compared with those over 50 years of age. The five-years survival of young CRCs patients with MSI 81.82%, was better than that of the patients with cancers with microsatellite stability, 60%, but there was no significant difference in statistics. Discussion and conclusion In our study there was no statistically detectable significant difference between tumor microsatellite status and survival in young patients, although we confirmed the previous observations that MSI is associated with better prognosis. We found that the pathological stage of CRC was an independent and powerful predictor of the clinical outcome.

Adverse Prognostic Effect of Methylation in Colorectal Cancer Is Reversed by Microsatellite Instability

2003 ◽  
Vol 21 (20) ◽  
pp. 3729-3736 ◽  
Author(s):  
Robyn Lynne Ward ◽  
Kay Cheong ◽  
Su-Lyn Ku ◽  
Alan Meagher ◽  
Terence O’Connor ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Microsatellite Instability ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Curative Surgery ◽  
Fresh Tissue ◽  
Vascular Space ◽  
Response To Chemotherapy ◽  
Vascular Space Invasion

Purpose: DNA methylation is an important biologic event in colorectal cancer and in some cases is associated with the development of microsatellite instability (MSI). In this study, we sought to determine the prognostic significance of DNA methylation, both in univariate analysis and in concert with other clinicopathologic factors known to influence outcome. Patients and Methods: Fresh tissue (625 cancers) was obtained from 605 individuals (age range, 29 to 99 years) undergoing curative surgery for colorectal cancer at one institution during a period of 8 years. Clinicopathologic details were recorded for all tumors, including stage, grade, type, vascular space invasion, and clinical follow-up to 5 years. Microsatellite status was assessed using standard markers. Methylation of p16 and hMLH1 promoters was determined by methylation-specific polymerase chain reaction (PCR), whereas methylation at methylated-in-tumor loci (MINT)1, MINT2, MINT12, and MINT31 loci were assessed by bisulfite-PCR. Results: Patients with microsatellite unstable tumors (12%) had better disease-specific survival than those with microsatellite stable (MSS) tumors (univariate analysis: hazard ratio [HR], 0.53; 95% CI, 0.27 to 1.0). Overall survival of individuals with MSS tumors was influenced by three independently significant factors: tumor stage (HR, 7.3; 95% CI, 5.1 to 10.4), heavy tumor methylation (HR, 2.1; 95% CI, 1.1 to 4.0), and vascular space invasion (HR, 1.9; 95% CI, 1.3 to 2.9). In MSS tumors, methylation at any single site was not independently predictive of survival. Neither methylation nor microsatellite status predicted a favorable response to chemotherapy. Conclusion: DNA methylation is associated with a worse outcome in colorectal cancer, but this adverse prognostic influence is lost in those methylated tumors showing MSI. The mechanisms of these events warrant additional investigation.

scholarly journals Low Level of Microsatellite Instability Correlates with Poor Clinical Prognosis in Stage II Colorectal Cancer Patients

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ehsan Nazemalhosseini Mojarad ◽  
Seyed Mohammad Hossein Kashfi ◽  
Hanieh Mirtalebi ◽  
Mohammad Yaghoob Taleghani ◽  
Pedram Azimzadeh ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Prognostic Significance ◽  
Tumor Stage ◽  
Cross Sectional Study ◽  
Stage Ii ◽  
Curative Surgery ◽  
Cross Sectional ◽  
Clinical Prognosis ◽  
Distinct Subgroup

The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance. In this study we found that MSI-H tumors were predominantly located in the colon versus rectum (p=0.03), associated with poorer differentiation (p=0.003) and TNM stage II/III of tumors (p=0.02). In CRC patients with stage II, MSI-L cases showed significantly poorer survival compared with patients who had MSI-H or MSS tumors (p=0.04). This study indicates that MSI-L tumors correlate with poorer clinical outcome in patients with stage II tumors (p=0.04) or in tumors located in the colon (p=0.02). MSI-L characterizes a distinct subgroup of CRC patients who have a poorer outcome. This study suggests that MSI status in CRC, as a clinical prognostic marker, is dependent on other factors, such as tumor stage and location.

Prognostic significance of pathological biomarkers in patients with stage II-III colorectal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14518-14518
Author(s):  
C. Funaioli ◽  
C. Pinto ◽  
C. Ceccarelli ◽  
F. Di Fabio ◽  
D. Cuicchi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Stage Iii ◽  
Disease Stage ◽  
Primary Tumor Site ◽  
The Impact

14518 Background: Biopathological colorectal cancer (CRC) studies have provided information on pathogenesis, but it is unclear how important biomarkers actually are in predicting prognosis. The aim of our study was to define the prognostic significance of biomarkers and a biopathological profile that could predict an increase in the disease relapse risk in stage II-III CRC patients (pts). Methods: The primary tumor of the CRC pts treated with surgery was immunohistochemically evaluated on the Ki67, p53, bcl-2, TS, EGFR, MLH1 and MSH2 expressions. All 7 markers were measured using standard immunohistochemical techniques. The biomarker evaluations were scored by just one pathologist. Results: Between March 2001 and October 2006 the primary tumor of 242 consecutive pts was investigated. Pt characteristics were: males 141(58.3%), females 101(41.7%); median age 68.5 (24–88); primary tumor site: right colon 94(38.8%), left colon 148(61.2%); stage II 102(42.1%), stage III 81(33.5%), stage IV 59(24.4%). 5-fluorouracil based adjuvant chemotherapy was performed in 121 (66.1%) pts. After a median follow up of 30 months (1–80), 34 pts (10 pts stage II, 24 pts stage III) of 183 stage II-III pts (18.6%) had a disease recurrence. In a univariate analysis of stage II-III pts, a higher expression of Ki67 (= 50% positive cells) was significantly associated with an improved DFS (p= 0.014) and overall survival (OS) (p=0.010). Expression of p53, bcl-2, TS, EGFR, MLH1 and MSH2 were not significantly associated with DFS and OS. In a multivariate analysis adjusted for the impact of the disease stage and adjuvant chemotherapy, a higher expression of Ki67 was significantly associated with diminished risk of recurrence (HR: 0.395; 95% CI: 0.183–0.855, p=0.018) and death (HR: 0.179; 95% CI: 0.046–0.696, p=0.013). The evaluation of DNA mismatch repair status (MLH1, MSH2) demonstrated that the lack of MLH1 is more frequent in non-relapsed II-III stage pts than in IV stage pts (p= 0.024). Conclusions: This analysis showed a significant correlation between higher Ki67 expression and better DFS and OS in pts with stage II-III CRC. An higher frequency of MLH1 deficiency was observed in non-relapsed pts with stage II-III than in advanced disease. No significant financial relationships to disclose.

scholarly journals The value of circulating fibrinogen-to-pre-albumin ratio in predicting survival and benefit from chemotherapy in colorectal cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110228
Author(s):  
Hou-Qun Ying ◽  
Fan Sun ◽  
Yu-Cui Liao ◽  
Dan Cai ◽  
Ying Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factor ◽  
Complete Response ◽  
Carbohydrate Antigen ◽  
Independent Prognostic Factor ◽  
Stage Iii ◽  
Low Grade ◽  
Response To Chemotherapy ◽  
Chemotherapy Efficacy

Background: To evaluate the prognostic role of circulating fibrinogen-to-pre-albumin (FPR) in colorectal cancer (CRC) with different tumor locations, and its involvement in chemosensitivity and chemoresistance. Patients and methods: A total of 2917 eligible CRC patients from multiple centers were enrolled in this prospective study, and 3 years follow-up was carried out to obtain the outcome of these patients. Circulating fibrinogen (Fib), pre-albumin (pAlb), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) were detected, and we calculated FPR according to the detected results. Kaplan–Meier curves, Cox proportional regression, time-dependent receiver operating characteristic curves, Harrell’s concordance index, calibration, and decision curves were used to investigate the role of FPR in predicting chemotherapy efficacy and prognosis of CRC patients. Results: Our results showed that cancer bulk, its infiltrating depth, and the distal metastasis status of CRC determined circulating FPR levels. A high FPR was associated with a significantly inferior prognosis, while the outcomes of right-sided patients with stage III and IV CRC were worse than left-sided cases. Only FPR was found to be a reliable and independent prognostic factor for each stage of CRC. In addition, the prognostic FPR-contained nomograms were superior to the non-FPR nomograms and FPR in predicting the outcomes in both localized and metastatic CRC patients. The circulating FPR was significantly associated with chemotherapeutic efficacy in stage III and IV CRC patients. In particular, low-grade (FPR < 15) and medium-grade (15 ⩽ FPR < 20) FPR patients exhibited a complete response to chemotherapy and attenuated chemosensitivity, respectively; in contrast, high-grade inflammation (FPR ⩾ 20) conferred resistance to the treatment. Conclusion: Circulating FPR is a robust and independent prognostic factor, a simple and economically-friendly predictor of chemotherapy efficacy within cases of localized and metastatic CRC. FPR-contained nomograms are more effective in predicting the prognosis of these patients. FPR and the nomogram can be recommended for the evaluation of chemotherapy efficacy and to aid decision-making associated with the management of these patients.

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