Fraction of LOH on chromosome 17 and 18 (LOH-ratio) predicts colorectal cancer outcome

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20114-20114
Author(s):  
T. Kanazawa ◽  
T. Watanabe ◽  
H. Nagawa

20114 Background: Identification of patients at high risk for recurrence remains a central issue in the treatment of colorectal cancer. Our goal was to identify predictive factors for recurrence in colorectal cancer patients. Methods: DNA from 84 colorectal cancers were analyzed for wide-ranging allelotyping. Using 27 microsatellite markers spanning every 10cM on chromosome 17 and 18, we defined the LOH-ratio as the proportion of markers which show LOH out of 27 markers. Tumors were grouped into two groups by the median value of LOH-ratio (0.19). Recurrence free survival was compared with Kaplan-Meier analysis and log rank statistic. The Cox proportional hazards regression model was used for both univariate and multivariate analysis of recurrence free survival. Results: Log rank statistic revealed that LOH-ratio, stage, lymph node metastasis significantly related to recurrence free survival. On univariate analysis, significant predictors of Recurrence free survival were LOH-ratio, lymph node metastasis, Dukes’ classification, and pathological type. On multivariate analysis, LOH-ratio (HR 3.1, p = 0.02) and lymph node metastasis (HR 5.2, p = 0.002) independently predicted for recurrence free survival. Conclusions: LOH-ratio and lymph node metastasis were the only independent predictors of recurrence free survival. Altogether with lymph node metastasis, LOH-ratio could help to improve postoperative surveillance and adjuvant therapy. No significant financial relationships to disclose.

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Hyungju Kwon ◽  
Byung-In Moon

Abstract Background Patients with Graves’ disease (GD) are at a 2.5 times higher risk of developing thyroid cancer than the general population. Previous studies reported conflicting results about the prognosis of thyroid cancer concomitant with GD. This study aimed to investigate the effect of GD to the recurrence rates of papillary thyroid carcinoma (PTC). Methods We reviewed 3628 patients who underwent total thyroidectomy for PTC at the Ewha Womans University Medical Center from January 2006 to June 2014. Of those, 114 patients had non-occult PTC with concomitant GD. To reduce potential confounding effects and selection bias, we conducted 1:5 propensity score matching and analyzed the recurrence-free survival. Results Thyroid cancer in patients with GD showed lower rate of lymphatic invasion (1.8% vs. 6.7%; p = 0.037), microscopic resection margin involvement (0.9% vs. 5.8%; p = 0.024), and lymph node metastasis (29.8% vs. 37.3%; p = 0.001) than in patients without GD, respectively. During the median follow-up of 94.1 months, recurrence occurred in one patient (0.9%) with GD. After propensity score matching for adjusting clinicopathological features, 5-year recurrence-free survival was comparable between patients with GD and euthyroid patients (100% vs. 98.4%, p = 0.572). Both tumor size [hazard ratio (HR) 1.585, p < 0.001] and lymph node metastasis (HR for N1a 3.067, p = 0.024; HR for N1b 15.65, p < 0.001) were predictive factors for recurrence-free survival, while GD was not associated with the recurrence. Conclusions Our data suggest that GD does not affect the prognosis of PTC. Thyroid cancer in patients with GD is not more aggressive than in euthyroid patients.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11038-11038
Author(s):  
Tadeu Ferreira Paiva ◽  
Alexandre Andre Balieiro Anastacio da Costa ◽  
Flavio Augusto Ismael Pinto ◽  
Victor Hugo Fonseca Jesus ◽  
Raul A. Marques ◽  
...  

11038 Background: There are no validated biomarkers for clinical response or survival benefit in patients treated with bevacizumab (Bv) in advanced metastatic colorectal cancer (mCRC). The aim of this study was to evaluate the predictive value of putative biomarkers in mCRC. Methods: One hundred and five mCRC patients who received Bv combined with FOLFOX or FOLFIRI were retrospectively evaluated for clinical and pathological characteristics. VEGFR1, VEGFR2, VEGFR3, PlGF, DLL4 and NOTCH1 expression were assessed by immunohistochemistry on formalin-fixed, paraffin-embedded neoplastic tissue of either primary or metastatic tissue in a tissue microarray. High levels of expression were defined as less than or equal to or more than the median. Survival curves were calculated by the Kaplan-Meier method and compared by the log-rank test. For multivariate analysis the Cox proportional hazards model was used. Results: Grade 1 or 2 (p=0.01), non-mucin-producing histology (p=0.04) and presence of liver metastasis (p=0.001) were associated with a higher response rate. There was no difference between the expression of markers and the response rate. ECOG 0 or 1 (p=0.002), grade 1 or 2 (p=0.02), liver metastasis (p=0.003), no lymph node metastasis (p=0.01) no peritoneal metastasis (p=0.02) and resection of metastasis (p<0.001) were correlated with higher progression-free survival (PFS). There was also a strong correlation between ECOG 0 or 1 (p=0.001), grade 1 or 2 (p=0.006), no lymph node metastasis (p=0.004), liver metastasis (p<0.001) and resection of metastasis (p<0.0001) with better overall survival. There was a trend between high expression of NOTCH1 (p=0.06) and worst PFS.High expression of VEGFR2 (p=0.07) was slightly associated with a better overall survival, while high expression of NOTCH1 was associated with a worse overall survival (p=0.01). Using multivariate analysis, NOTCH1 proved to be an independent variable for adverse overall survival (HR 2.01, IC 1.07 – 3.77, p=0.02). Conclusions: High NOTCH1 expression assessed by immunohistochemistry is capable of predicting poor survival in advanced colorectal cancer patients treated with bevacizumab.


2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 200s-200s
Author(s):  
K. Lee

Background: ASXL1 gene is on chromosome region 20q11.21. Either amplification in cervical cancer or truncation mutations in colorectal cancers with microsatellite instability (MSI), malignant myeloid diseases, chronic lymphocytic leukemia, liver, prostate and breast cancers occurred. The functional and the prognostic roles of ASXL1 mutations and the expression of protein in colorectal cancer are still unknown. Aim: The aim of this study is to investigate the functional roles of ASXL1 mutations and the expression of protein in colorectal cancer. Methods: We performed NGS of 10 colorectal cancer with peritoneal seeding to find genetic markers for aggressive phenotype. All showed a frameshift deletion at codon 1934delG. To clinically validate the functional and the prognostic roles of the mutations, we performed an immunohistochemical staining (IHC) on tissue microarrays of 414 consecutive colorectal cancers. Results: The ASXL1 protein expression was strong positive in 5.8% (24 patients), moderate positive in 38.5% (157 patients) and negative in 55.6% (227 patients). The patients with negative ASXL1 expression had more lymph node metastasis than the patients with strong positive expression [59.0% (134/227 patients) vs 33.3% (8/24 patients), P = 0.038]. None of the patients with strong positive expression had recurrent disease in the stage I-III cancers [0% (0/21 patients) vs 19.4% (27/139 patients) vs 18.9% (34/180 patients)] and the disease-free survival rate of the patients with strong positive expression was significantly better than that of the patients with moderate positive or negative expression ( P = 0.037; P = 0.031). Conclusion: The decreased level of the expression of the ASXL1 protein was associated with lymph node metastasis in its progression of cancer. Strong positive ASXL1 protein expression was a 'good' prognostic factor of colorectal cancers. The ASXL1 protein might be tumor suppressive in colorectal cancer.


BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e027185 ◽  
Author(s):  
Yun Hong Ren ◽  
Feng Juan Zhao ◽  
Han Yue Mo ◽  
Rong Rong Jia ◽  
Juan Tang ◽  
...  

ObjectivesLiver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and prognosis is controversial. This review aimed to quantitatively examine the latest evidence on this question.DesignAn updated systematic review and meta-analysis on the association between LKB1 expression and prognosis of patients with solid tumours were performed.Data sourcesEligible studies were identified through literature searches from database establishment until 15 June 2018 in the following databases: Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases.Eligibility criteriaThe association between LKB1 expression and clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) of patients with solid tumours were reported. Sufficient data were available to calculate the OR or HR and 95% CI.Data extraction and synthesisRelevant data were meta-analysed for OS, DFS, RFS and various clinical parameters.ResultsThe systematic review included 25 studies containing 6012 patients with solid tumours. Compared with patients with high LKB1 expression, patients with low expression showed significantly shorter OS in univariate analysis (HR=1.63, 95% CI 1.35 to 1.97, p<0.01) and multivariate analysis (HR=1.61, 95% CI 1.26 to 2.06, p<0.01). In contrast, the two groups showed similar DFS in univariate analysis (HR=1.49, 95% CI 0.73 to 3.01, p=0.27) as well as similar RFS in univariate analysis (HR=1.44, 95% CI 0.65 to 3.17, p=0.37) and multivariate analysis (HR=1.02, 95% CI 0.42 to 2.47, p=0.97). Patients with low LKB1 expression showed significantly worse tumour differentiation (OR=1.71, 95% CI 1.14 to 2.55, p<0.01), larger tumours (OR=1.68, 95% CI 1.24 to 2.27, p<0.01), earlier lymph node metastasis (OR=1.43, 95% CI 1.26 to 1.62, p<0.01) and more advanced tumour, node, metastases (TNM) stage (OR=1.80, 95% CI 1.56 to 2.07, p<0.01).ConclusionLow LKB1 expression predicts shorter OS, worse tumour differentiation, larger tumours, earlier lymph node metastasis and more advanced TNM stage. Low LKB1 expression may be a useful biomarker of poor clinicopathology and prognosis.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14559-14559
Author(s):  
S. Takahashi ◽  
T. Kinoshita ◽  
N. Saito ◽  
M. Sugitoh ◽  
A. Ochiai

14559 Background: Rare occurrence of CLM was reported in patients (pts) with HBV or HCV infection, or liver cirrhosis (LC). However, it is obscure whether HBV or HCV infection itself influence occurrence of CLM irrespective of liver cirrhosis (LC). The aim of this retrospective study was to evaluate correlation between HBV or HCV infection and occurrence of CLM. Methods: Subjects of this study were colorectal carcinomas treated by curative resection at our institution between Nov ’92 and Dec ’01 and fulfilled the following criteria; TNM Stage I-III, histologically confirmed colorectal adenocarcinoma, having definitive results of preoperative tests for HB surface antigen (HBsAg) and HCV antibody, and no LC. Results: A total of 1040 pts met the recruitment criteria. Eleven and 60 pts were positive for HBsAg and HCV antibody respectively. Both HBsAg and HCV antibody were negative in the remaining 969 pts. Comparing characteristics between the infection group and the non-infection group, stage (I/II/III: 19/31/21, 305/306/358), lymph node metastasis (present/absent: 51/20, 607/362), histological type (well, mod/por, others: 62/9, 895/74) depth of tumor (T1,T2/T3,T4: 21/50, 358/611), and preoperative CEA level (ng/ml: 6.5±7.5, 9.2±24.6) did not differ between two groups significantly by the chi-square test (stage, lymph node metastasis, histological type, and depth of tumor) and Mann-Whitney’s U test (CEA). Hepatic function of the infection group was slightly worse than those of the non-infection group by student t-test; alb (g/dl: 3.8±0.5, 4.0±0.4, p<0.01), t-bil (mg/dl: 0.8±0.4, 0.7±0.3, p<0.01). When correlations between hepatic recurrence-free survival and clinicopathological factors were examined, depth of tumor (T3.T4), lymph node metastasis, and alb < 3.8g/dl were the independent poor prognostic factors by the Cox regression model. HBV or HCV infection did not correlate with hepatic recurrence-free survival, recurrence- free survival, or overall survival. Conclusions: HBV or HCV infection does not influence on occurrence of CLM. No significant financial relationships to disclose.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 965
Author(s):  
Selina Hiss ◽  
Markus Eckstein ◽  
Patricia Segschneider ◽  
Konstantinos Mantsopoulos ◽  
Heinrich Iro ◽  
...  

Objectives: The aim of this study was to assess the number of tumour-infiltrating lymphocytes (TILs) and the expression of Programmed Cell Death 1 Ligand 1 (PD-L1) in Acinic Cell Carcinoma (AciCC) of the salivary glands, to enable a correlation with clinico-pathological features and to analyse their prognostic impact. Methods: This single centre retrospective study represents a cohort of 36 primary AciCCs with long-term clinical follow-up. Immunohistochemically defined immune cell subtypes, i.e., those expressing T-cell markers (CD3, CD4 and CD8) or a B-cell marker (CD20) were characterized on tumour tissue sections. The number of TILs was quantitatively evaluated using software for digital bioimage analysis (QuPath). PD-L1 expression on the tumour cells and on immune cells was assessed immunohistochemically employing established scoring criteria: tumour proportion score (TPS), Ventana immune cell score (IC-Score) and combined positive score (CPS). Results: Higher numbers of tumour-infiltrating T- and B- lymphocytes were significantly associated with high-grade transformation. Furthermore, higher counts of T-lymphocytes correlated with node-positive disease. There was a significant correlation between higher levels of PD-L1 expression and lymph node metastases as well as the occurrence of high-grade transformation. Moreover, PD-L1 CPS was associated with poor prognosis regarding metastasis-free survival (p = 0.049). Conclusions: The current study is the first to demonstrate an association between PD-L1 expression and lymph node metastases as well as grading in AciCCs. In conclusion, increased immune cell infiltration of T and B cells as well as higher levels of PD-L1 expression in AciCC in association with high-grade transformation, lymph node metastasis and unfavourable prognosis suggests a relevant interaction between tumour cells and immune cell infiltrates in a subset of AciCCs, and might represent a rationale for immune checkpoint inhibition.


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