scholarly journals Prognostic significance of MUC2, CDX2 and SOX2 in stage II colorectal cancer patients

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara Ribeirinho-Soares ◽  
Diana Pádua ◽  
Ana Luísa Amaral ◽  
Elvia Valentini ◽  
Daniela Azevedo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Significance ◽  
Tumor Resection ◽  
Disease Free Survival ◽  
Predictive Biomarkers ◽  
Stage Ii ◽  
Health Concern ◽  
Rank Test ◽  
Low Expression

Abstract Background Colorectal cancer (CRC) remains a serious health concern worldwide. Despite advances in diagnosis and treatment, about 15 to 30% of stage II CRC patients subjected to tumor resection with curative intent, develop disease relapse. Moreover, the therapeutic strategy adopted after surgery is not consensual for these patients. This supports the imperative need to find new prognostic and predictive biomarkers for stage II CRC. Methods For this purpose, we used a one-hospital series of 227 stage II CRC patient samples to assess the biomarker potential of the immunohistochemical expression of MUC2 mucin and CDX2 and SOX2 transcription factors. The Kaplan-Meier method was used to generate disease-free survival curves that were compared using the log-rank test, in order to determine prognosis of cases with different expression of these proteins, different mismatch repair (MMR) status and administration or not of adjuvant chemotherapy. Results In this stage II CRC series, none of the studied biomarkers showed prognostic value for patient outcome. However low expression of MUC2, in cases with high expression of CDX2, absence of SOX2 or MMR-proficiency, conferred a significantly worst prognosis. Moreover, cases with low expression of MUC2 showed a significantly clear benefit from treatment with adjuvant chemotherapy. Conclusion In conclusion, we observe that patients with stage II CRC with low expression of MUC2 in the tumor respond better when treated with adjuvant chemotherapy. This observation supports that MUC2 is involved in resistance to fluorouracil-based adjuvant chemotherapy and might be a promising future predictive biomarker in stage II CRC patients.

Analysis of RGS2 expression and prognostic significance in stage II and III colorectal cancer

2010 ◽  
Vol 30 (6) ◽  
pp. 383-390 ◽  
Author(s):  
Zheng Jiang ◽  
Zhimin Wang ◽  
Ye Xu ◽  
Beilan Wang ◽  
Wei Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mrna Expression ◽  
Survival Time ◽  
Cell Lines ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Rank Test ◽  
Clinicopathological Factors ◽  
Real Time Quantitative Pcr

The role of RGS2 (regulator of G-protein signalling 2) has been studied in several tumours. The purpose of the present study is to investigate the correlations between clinicopathological factors and patients' survival time and RGS2 expression in stage II and III CRC (colorectal cancer) patients. Real-time quantitative PCR was performed in 36 CRC tissues with recurrence and 28 without recurrence, and in three CRC-metastasis-derived cell lines (SW620, LoVo and Colo205) and 3 primary-CRC-derived ones (SW480, Caco-2 and HCT116) to examine RGS2 mRNA expression. In addition, to provide visualized evidence for RGS2 mRNA expression, random CRC samples were also performed with RT–PCR (reverse transcription–PCR). RGS2 protein was detected by immunostaining in 118 paraffin-embedded specimens, and the correlations between clinicopathological factors and survival time and RGS2 expression were analysed. We found that RGS2 mRNA was down-regulated both in CRC tissues with recurrence and metastasis-derived cell lines, and the expression level of RGS2 was unrelated to gender, age, tumour grade, or lymphovascular or perineural invasion. However, it was positively related to disease-free survival time (P<0.05). Furthermore, low RGS2 expression indicated a poorer survival rate (P<0.05, log-rank test). Multivariate analysis also showed that weak RGS2 protein expression was an independent adverse prognosticator in CRC (P<0.05). Taken together, we suggested that down-regulation of RGS2 might play an important role in CRC metastasis and predict poor prognosis in stage II and III CRC patients.

scholarly journals Lymphopenia associated with adjuvant chemotherapy after potentially curative surgery for colorectal cancer correlates with recurrence

2016 ◽  
Author(s):  
Masatsune Shibutani ◽  
Kiyoshi Maeda ◽  
Hisashi Nagahara ◽  
Hiroshi Ohtani ◽  
Tetsuro Ikeya ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Adjuvant Chemotherapy ◽  
Lymphocyte Count ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Curative Surgery ◽  
Free Survival ◽  
Background Data ◽  
Disease Free

Abstract Objective: The aim of this retrospective study was to evaluate the prognostic significance of lymphopenia associated with chemotherapy in patients with colorectal cancer who received adjuvant chemotherapy after undergoing potentially curative surgery. Summary of background data: Lymphocyte plays an important role in anti-tumor immunity. Lymphopenia is sometimes induced during the period of adjuvant chemotherapy after potentially curative surgery for colorectal cancer. However, the prognostic significance of lymphopenia associated with chemotherapy is unknown. Methods: One hundred and fifteen patients who received adjuvant chemotherapy after potentially curative surgery for stage II/III colorectal cancer were enrolled in this study. All patients were classified into two groups, the lymphopenia group and the normal group, according to minimum lymphocyte count during the period of adjuvant chemotherapy. Lymphopenia was defined as a lymphocyte count of less than 1,000/Ã&#x8e;¼l. Lymphopenia associated with chemotherapy was found in 17 of the 115 patients (14.8%). Results: Lymphopenia was associated with a worse disease-free survival (p=0.018). Moreover, in a multivariate analysis, lymphopenia associated with chemotherapy was identified to be an independent prognostic factor.

scholarly journals Prognostic significance of S100A4 expression in stage II and III colorectal cancer: results from a population‐based series and a randomized phase III study on adjuvant chemotherapy

2016 ◽  
Vol 5 (8) ◽  
pp. 1840-1849 ◽  
Author(s):  
Kjetil Boye ◽  
Havjin Jacob ◽  
Kari‐Anne M. Frikstad ◽  
Jahn M. Nesland ◽  
Gunhild M. Mælandsmo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Significance ◽  
Population Based ◽  
Stage Ii ◽  
Phase Iii ◽  
S100a4 Expression ◽  
Phase Iii Study

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 The platelet to lymphocyte ratio is a potential inflammatory marker predicting the effects of adjuvant chemotherapy in patients with stage II colorectal cancer

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Fu ◽  
Xiaowan Chen ◽  
Yongxi Song ◽  
Xuanzhang Huang ◽  
Quan Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Treatment Effect ◽  
Inflammatory Marker ◽  
Stage Ii ◽  
Rank Test ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Stage Ii Colorectal Cancer ◽  
Chemotherapy Patients

Abstract Background The effects of adjuvant chemotherapy in patients with stage II colorectal cancer (CRC) has been in controversy for a long time. Our study aimed to find an effective inflammatory marker to predict the effects of chemotherapy. Methods Seven hundred eight stage II CRC patients in our institution were included. The subpopulation treatment effect pattern plot (STEPP) analysis was used to determine the optimal inflammatory marker and cut-off value. Propensity score matching (PSM) was performed to balance discrepancy between the chemotherapy and non-chemotherapy group. Survival analyses based on overall survival (OS) and cancer-specific survival (CSS) were performed with Kaplan-Meier methods with log-rank test and Cox proportional hazards regression. The restricted mean survival time (RMST) was used to measure treatment effect. Results The platelet to lymphocyte ratio (PLR) was chosen as the optimal marker with a cut-off value of 130 according to STEPP. In OS analysis, PLR was significantly associated with the effects of chemotherapy (interaction p = 0.027). In the low-PLR subgroup, the chemotherapy patients did not have a longer OS than the non-chemotherapy patients (HR: 0.983, 95% CI: 0.528–1.829). In the high-PLR subgroup, the chemotherapy patients had a significantly longer OS than the non-chemotherapy patients (HR: 0.371, 95% CI: 0.212–0.649). After PSM, PLR was still associated with the effects of chemotherapy. In CSS analysis, PLR was not significantly associated with the effects of chemotherapy (interaction p = 0.116). In the low-PLR subgroup, the chemotherapy patients did not have a longer CSS than the non-chemotherapy patients (HR: 1.016, 95% CI: 0.494–2.087). In the high-PLR subgroup, the chemotherapy patients had a longer CSS than the non-chemotherapy patients (HR: 0.371, 95% CI: 0.212–0.649). After PSM, PLR was not associated with the effects of chemotherapy. Conclusions PLR is an effective marker to predict the effects of chemotherapy in patients with stage II CRC.

scholarly journals Implications of Habitual Alcohol Intake With the Prognostic Significance of Mean Corpuscular Volume in Stage II-III Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Qi Liu ◽  
Yufei Yang ◽  
Xinxiang Li ◽  
Sheng Zhang
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Factors ◽  
Mean Corpuscular Volume ◽  
Alcohol Intake ◽  
Prognostic Significance ◽  
Stage Ii ◽  
Rank Test ◽  
Corpuscular Volume ◽  
Prognostic Role ◽  
Increased Risk

ObjectiveTo elucidate the prognostic significance of mean corpuscular volume (MCV), with implications of habitual alcohol intake in stage II-III colorectal cancer (CRC).BackgroundMCV had the potential to become an ideal prognostic biomarker and be put into clinical application. Few studies, however, have explored whether habitual alcohol intake which greatly increased the value of MCV would affect the prognostic role of MCV.MethodsEligible patients were identified from the CRC database of Fudan University Shanghai Cancer Center (FUSCC) between January 2012 and December 2013. Survival analyses were constructed using the Kaplan–Meier method to evaluate the survival time distribution, and the log-rank test was used to determine the survival differences. Univariate and multivariate Cox proportional hazard models were built to calculate the hazard ratios of different prognostic factors.ResultsA total of 694 patients diagnosed with stage II-III CRC between January 2012 and December 2013 were identified from FUSCC. Low pretreatment MCV was independently associated with 72.0% increased risk of overall mortality compared with normal MCV (HR = 1.720, 95%CI =1.028-2.876, P =0.039, using normal MCV as the reference). In patients with habitual alcohol intake, however, pretreatment MCV positively correlated with the mortality (P = 0.02) and tumor recurrence (P = 0.002) after adjusting for other known prognostic factors.ConclusionsIn CRC patients without habitual alcohol intake, low (&lt;80 fL) level of pretreatment MCV was a predictor of poor prognosis. In patients with habitual alcohol intake, however, pretreatment MCV showed the opposite prognostic role, which would elicit many fundamental studies to elucidate the mechanisms behind.

Tumor Diameter Is an Easy and Useful Predictor of Recurrence in Stage II Colorectal Cancer

2015 ◽  
Vol 32 (5) ◽  
pp. 338-343 ◽  
Author(s):  
Chiyo Maeda ◽  
Eiji Hidaka ◽  
Yuichi Mori ◽  
Shumpei Mukai ◽  
Hideyuki Miyachi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Multivariate Analysis ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Venous Invasion ◽  
Stage Ii ◽  
Tumor Diameter ◽  
Free Survival ◽  
Stage Ii Colorectal Cancer

Background/Aims: Adjuvant chemotherapy for stage II colorectal cancer (CRC) can generally be administered to high-risk subgroups. To better identify these patients, we aimed at assessing factors that affect recurrence. Methods: In our hospital, 432 colon and 96 rectal stage II cancer patients who underwent surgical resection between 2001 and 2011 were divided into recurrence and non-recurrence groups. Age, sex, lymphatic vessel invasion, venous invasion, tumor diameter, tumor depth, histological type, preoperative carcinoembryonic antigen level, number of sampled nodes, adjuvant chemotherapy, morphology, surgical approach, anastomotic leakage, preoperative bowel obstruction, and preoperative perforation were retrospectively compared between the groups. Results: For colon cancer, multivariate analysis revealed a significant association between tumor diameter ≥40 mm and recurrence (p = 0.039). For rectal cancer, multivariate analysis revealed that tumor diameter ≥50 mm (p = 0.001) and ≤12 sampled nodes (p = 0.021) were associated with recurrence. Tumor diameter in rectal cancer was associated with worse disease-free survival (p = 0.026). Conclusion: Tumor diameter is a significant predictor of recurrence in stage II CRC. This is an important finding because tumor diameter is easy to evaluate clinically and might help to identify candidates for adjuvant chemotherapy.

Prognostic Significance of CEA and CA 19–9 inc Colorectal Cancer in Kuwait

2000 ◽  
Vol 15 (1) ◽  
pp. 51-55 ◽  
Author(s):  
A.I. Behbehani ◽  
H. Al-Sayer ◽  
M. Farghaly ◽  
N. Kanawati ◽  
A. Mathew ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Prognostic Indicators ◽  
Chi Square ◽  
Free Survival ◽  
Significant Difference ◽  
Disease Free ◽  
Dukes C

Preoperative CEA and CA 19–9 levels have been used in the past as prognostic indicators in colorectal cancer, but Dukes’ stage is still considered to be the most important prognostic factor. Recent survival estimates may have been influenced by the fact that in the last decade adjuvant chemotherapy and postoperative irradiation have been included in the routine management of advanced-stage disease. In a heterogeneous Kuwaiti population higher reference levels (95th percentile) of CEA and CA 19–9 have been found than those usually employed. In the present study 62 patients with Dukes’ stage B + C could be analyzed for two-year disease-free survival (DFS). Relapse was observed in 19 patients, 28 patients were disease free and 15 patients with censored observations were included. No significant difference in DFS was observed in Dukes’ B (69%) versus Dukes’ C (48%) patients (p=0.09). On the other hand, Dukes’ stage B+C patients with elevated preoperative levels of CEA or CA 19–9 had a significantly poorer DFS than patients with normal levels. For CEA levels below or above the cutoff the DFS was 74% versus 23% (p=0.003); for CA 19–9 levels below or above the cutoff the DFS was 71% versus 33% (p=0.004). In 54 patients with Dukes’ stage B+C for whom preoperative levels of both CEA and CA 19–9 were available multivariate analysis revealed a decreasing risk of relapse in the following order: CEA and/or CA 19–9 elevated (chi-square 7.09; p=0.008), CA 19–9 elevated (chi-square 6.27; p=0.01), CEA elevated (chi-square 5.47; p=0.02), and Dukes’ C (chi-square 2.08; p=0.15 n.s.). Hence, novel treatment protocols may have improved the disease-free survival, but the use of adjuvant chemotherapy and/or radiotherapy is of questionable benefit in patients who have elevated levels of CEA and/or CA 19–9 prior to treatment.

Thymidylate Synthase Expression and Prognosis in Colorectal Cancer: A Meta-Analysis of Colorectal Cancer Survival Data

2012 ◽  
Vol 27 (3) ◽  
pp. 203-211 ◽  
Author(s):  
Yao Chen ◽  
Cuihua Yi ◽  
Lian Liu ◽  
Bei Li ◽  
Yawei Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Thymidylate Synthase ◽  
Survival Data ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

Background Although many studies have investigated the prognostic effect of thymidylate synthase (TS) in colorectal cancer, no consensus has been reached. The aim of this meta-analysis was to obtain a more precise estimate of the prognostic significance of TS expression in localized cancers treated by curative resection and adjuvant chemotherapy. Materials and method Seventeen eligible studies reporting survival in 2,893 patients stratified by TS expression were pooled using a fixed- or random-effects model. The main outcome measure was hazard ratio (HR). Results The overall HR for overall survival was 1.01 (95% CI 0.74–1.39, p=0.947), with an I2 of 64.4%. The total HR for disease-free survival was 1.36 (95% CI 0.97–1.89, p=0.072), with an I2 of 75.8%. In the TS protein-tested subgroup, the total HR for disease-free survival was 1.72 (95% CI 1.02–2.89, p=0.042), with an I2 of 81.3%. Conclusion Our meta-analysis showed that, in the adjuvant setting, TS expression does not predict a poorer disease-free survival or a worse overall survival. Therefore, we believe that it is inappropriate to regard TS expression as a prognostic factor for patients with stage II and stage III colorectal cancer treated by surgery and adjuvant chemotherapy.

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.

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