scholarly journals Mikroszatellita-instabilitás előfordulása, intratumoralis heterogenitása, prognosztikus és prediktív potenciálja primer colorectalis carcinomák és párosított májáttéteik sebészi kezelését követően

2015 ◽  
Vol 156 (36) ◽  
pp. 1460-1471 ◽  
Author(s):  
Emese Irma Ágoston ◽  
Zsolt Baranyai ◽  
Kristóf Dede ◽  
György Bodoky ◽  
Janina Kulka ◽  
...  
Keyword(s):  
Overall Survival ◽  
Molecular Markers ◽  
Mismatch Repair ◽  
Staining Intensity ◽  
Response To Therapy ◽  
Clinicopathological Parameters ◽  
Colorectal Carcinomas ◽  
Therapy Regimen ◽  
Methylator Phenotype ◽  
Mismatch Repair Status

Introduction: Besides clinicopathological parameters, molecular markers can be very important, and further characterize colorectal carcinomas into chromosomally unstable, microsatellite instable and “CqG-island methylator phenotype” groups. Aim: To study the frequency of microsatellite instability using immunohistochemical evaluation of MLH1, MSH2, MSH6 and PMS2 proteins in colorectal carcinoma. Method: 122 colorectal carcinomas as well as in 69 paired liver metastases were evaluated. Additionally, prognostic and predictive potential of mismatch repair status was tested. Results: Microsatellite instable phenotype was identified in 11.5% (14/122) of the tumours. There were no differences regarding staining intensity of tumour regions. Mismatch repair status was discordant in primaries vs. metastases in 20.2%. There was no difference in progression free- and overall survival according to mismatch repair status. The mismatch repair status was not predictive for survival within systemic therapy regimen groups. Conclusions: The subgroups of colorectal carcinomas could be evaluated in a larger and homogenised patient cohort to predict prognosis and response to therapy. Orv. Hetil., 2015, 156(36), 1460–1471.

scholarly journals Deciding the operation type according to mismatch repair status among hereditary nonpolyposis colorectal cancer patients: should a tailored approach be applied, or does one size fit all?

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chun-Kai Liao ◽  
Yueh-Chen Lin ◽  
Yu-Jen Hsu ◽  
Yih-Jong Chern ◽  
Jeng-Fu You ◽  
...  
Keyword(s):  
Overall Survival ◽  
Protein Expression ◽  
Mismatch Repair ◽  
Multivariate Analyses ◽  
Extent Of Resection ◽  
Significant Difference ◽  
Tailored Approach ◽  
Mismatch Repair Status ◽  
Colorectal Cancer Patients

Abstract Background Although extended colectomy (EC) was recommended for HNPCC patients, previous studies did not show significantly improved overall survival. Immunohistochemical (IHC) stain of mismatch repair (MMR) gene protein expression is now a feasible and reliable test clinically. Therefore, we tried to investigate whether we could use MMR IHC stain to select operation types in HNPCC patients. Patients and methods Between 1995 and 2013, 186 HNPCC patients were collected. Status of MMR protein expression, perioperative clinic-pathological variables and post-operative follow up status were analyzed by multivariate analyses. Results Sixty-five percent (121 of 186) patients of these HNPCC patients demonstrated loss of at least one MMR protein. There were several significant differences existing between deficient MMR (dMMR) and proficient MMR (pMMR) subgroups in terms of clinic-pathological characteristics. With the average follow-up duration of 93.9 months, we observed significantly high risk of developing metachronous CRC between SC and EC subgroups (crude rate 8.5% vs. 0%, p = 0.035). However, no significant difference was observed among the presence of extra-colonic tumors (12.4% vs. 5.8%, p = 0.284). The positive and negative prediction rate of metachronous CRC in dMMR subgroup was 12.8 and 87.2% while 1.9 and 98.1% in the pMMR subgroup. Survival outcomes were significantly affected by MMR status and resection types by multivariate analysis. Significantly better OS in dMMR subgroup (HR = 0.479, 95% CI: 0.257–0.894, p = 0.021) comparing with pMMR subgroup was observed. However, significant improved DFS (HR = 0.367, 95% CI: 0.172–.0787, p = 0.010) but not significant for OS (HR = 0.510, 95% CI: 0.219–1.150, p = 0.103) for EC subgroup compared with SC subgroup. Differences existing among different subgroups by combing extent of resection and MMR status. In dMMR subgroup, SC, compared with EC, demonstrated significantly worse DFS by multivariate analyses (HR = 3.526, 95% CI: 1.346–9.236, p = 0.010) but not for OS (HR = 2.387, 95% CI: 0.788–7.229, p = 0.124), however, no significantly differences of OS and DFS in pMMR subgroup between SC and EC were found. Conclusions Significantly better overall survival and higher rate of metachronous CRC exist in dMMR subgroup of HNPCC patients comparing with pMMR subgroup. Extended colectomy significantly improved DFS and was thus recommended for dMMR subgroup but not pMMR subgroup of HNPCC patients.

scholarly journals Resistance to chemotherapy and hormone therapy in endometrial cancer

2009 ◽  
Vol 16 (2) ◽  
pp. 363-380 ◽  
Author(s):  
Parvesh Chaudhry ◽  
Eric Asselin
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
Molecular Markers ◽  
Hormone Therapy ◽  
Signaling Pathways ◽  
Developed Countries ◽  
Response To Therapy ◽  
Extensive Literature ◽  
Gynecological Malignancy ◽  
Number Of Patients

Endometrial cancer is the most common gynecological malignancy in developed countries and represents the eighth leading cause of cancer related death in women. The growing incidence of endometrial cancer leads scientists and oncologists to identify effective preventive measures and also molecular markers for diagnosis and prognosis. Chemotherapy and hormone therapy is the mainstay treatment option for advanced and recurrent endometrial cancer and response to therapy is one of the most important factor which favors prognosis and overall survival. In recent years, there have been major advances in the treatment of patients with endometrial cancer. Despite advances made in the treatment of this cancer, the overall survival of patients has not significantly improved because considerable number of patients harbor tumor refractory to these therapies and the majority of the initially responsive tumors become refractory to treatments. Therefore, determination of sensitivity/resistance is becoming increasingly important for individualization of endometrial cancer therapy. The aim of this review is to present the existing knowledge about the molecular markers that could play a crucial role in determining resistance to chemo- and hormone therapy. Extensive literature search for the cell signaling pathways and factors responsible for chemoresistance have been performed and reviewed. Several recent studies suggest that deregulations in the apoptotic pathways (such as p53, Fas/FasL, Bcl-2 family proteins, inhibitor of apoptosis proteins), survival pathways (PI3K/AKT, MAPK), hormone receptor signaling pathways (progesterone receptor), Cyclooxygenase-2 and Her-2 are considered as key factors involved in the onset and maintenance of therapeutic resistance, suggesting that resistance is a multi-factorial phenomenon.

scholarly journals KK-LC-1 may be an effective prognostic biomarker for gastric cancer

2020 ◽  
Author(s):  
Jun Ji ◽  
Jiahui Chen ◽  
Anqiang Wang ◽  
Wei Zhang ◽  
Hongge Ju ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Staining Intensity ◽  
Good Prognosis ◽  
Clinicopathological Parameters ◽  
Chi Square ◽  
Clinical Prognosis ◽  
Cox Regression Analysis ◽  
Normal Tissues

Abstract Background: To detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyze the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. Methods: A total of 94 patients with GC who underwent surgical resection were enrolled in this study. The expression of KK-LC-1 in GC tissues was detected by immunohistochemistry. The assessment of KK-LC-1 expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of KK-LC-1 in the cytoplasm and was scored to achieve respective H-score values. The correlations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. Results: In the cytoplasm, the expression of KK-LC-1 in tumor tissues was significantly higher than that in normal tissues (P < 0.001, respectively). Using the median H-score as the cutoff value, it was discovered that, GC patients with higher levels of KK-LC-1expression in the cytoplasm, had favorable overall survival (P =0.016), and it was still statistically meaningful in Cox regression analysis. At the same time, the study found that there was a negative correlation between KK-LC-1’s protein expression and the pathological grade of the tumor (P = 0.036). Conclusions: Our research data shows that KK-LC-1’s expression in GC is higher than that of normal tissues, which is associated with a longer overall survival in GC. KK-LC-1 can be used as a biomarker for GC patients with good prognosis.

scholarly journals Significant Associations of Mismatch Repair Gene Polymorphisms With Clinical Outcome of Pancreatic Cancer

2009 ◽  
Vol 27 (10) ◽  
pp. 1592-1599 ◽  
Author(s):  
Xiaoqun Dong ◽  
Li Jiao ◽  
Yanan Li ◽  
Douglas B. Evans ◽  
Huamin Wang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Clinical Outcome ◽  
Mismatch Repair ◽  
Cellular Response ◽  
Tumor Response ◽  
Tumor Resection ◽  
Response To Therapy ◽  
Mismatch Repair Gene ◽  
Mmr Genes

Purpose DNA mismatch repair (MMR) is critical in maintaining genomic stability and may modulate the cellular response to gemcitabine. We hypothesized that genetic variations in MMR may affect the clinical outcome of patients with pancreatic cancer. Patients and Methods We evaluated 15 single-nucleotide polymorphisms (SNPs) of eight MMR genes in 154 patients with potentially resectable pancreatic adenocarcinoma who were enrolled onto phase II clinical trials for preoperative gemcitabine-based chemoradiotherapy from 1999 to 2006. Associations of genotypes with tumor response to therapy (change of tumor size by radiologic evaluation at restaging), margin-negative tumor resection, and overall survival were evaluated using logistic regression and Cox proportional regression models. Results Five, six, and 10 genotypes were significantly associated with tumor response to preoperative chemoradiotherapy, tumor resectability, and overall survival, respectively, in univariable analysis. TREX1 EX14-460C>T and TP73 Ex2+4G>A genotypes remained as significant predictors for tumor response, MLH1 IVS12-169C>T and TP73 remained as significant predictors for tumor resectability, and EXO1 R354H, TREX1, and TP73 remained as significant predictors for overall survival in multivariable models that included all clinical factors and genotypes examined. A strong combined genotype effect on each clinical end point was observed. For example, 20 of the 25 patients with zero to one adverse genotypes were alive, those with two, three, four, five, and six to seven adverse genotypes had median survival times of 36.2, 23.9, 16.3, 13.0, and 8.3 months, respectively (P < .001). Conclusion SNPs of MMR genes have a potential value as predictors for clinical response to chemoradiotherapy and as prognostic markers for tumor resectability and overall survival of patients with resectable pancreatic cancer.

scholarly journals KK-LC-1 may be an effective prognostic biomarker for gastric cancer

2021 ◽  
Author(s):  
Jun Ji ◽  
Jiahui Chen ◽  
Anqiang Wang ◽  
Wei Zhang ◽  
Hongge Ju ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Staining Intensity ◽  
Intestinal Type ◽  
Clinicopathological Parameters ◽  
Diffuse Type ◽  
Clinical Prognosis ◽  
Cox Regression Analysis ◽  
Normal Tissues

Abstract Background: To detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyze the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. Methods : A total of 94 patients with GC who underwent surgical resection were enrolled in this study. The expression of KK-LC-1 in GC tissues was detected by immunohistochemistry. The assessment of KK-LC-1 expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of KK-LC-1 in the cytoplasm and was scored to achieve respective H-score values. The correlations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. Results: In the cytoplasm, the expression of KK-LC-1 in tumor tissues was significantly higher than that in normal tissues (P < 0.001, respectively). Using the median H-score as the cutoff value, it was discovered that, GC patients with higher levels of KK-LC-1expression in the cytoplasm, had favorable overall survival (P =0.016), and it was still statistically meaningful in Cox regression analysis. At the same time, the study found that there was a negative correlation between KK-LC-1’s protein expression and the pathological grade of the tumor (P = 0.036); KK-LC-1 protein is more highly expressed in the intestinal type than the diffuse type, and it is statistically significant. The high expression of KK-LC-1 protein in the intestinal type is more than that in the diffuse type (P =0.008). Conclusions: Our research data shows that KK-LC-1’s expression in GC is higher than that of normal tissues, which is associated with a longer overall survival in GC. KK-LC-1 can be used as a biomarker for GC patients with good prognosis.

scholarly journals The Survivin −31 Snp in Human Colorectal Cancer Correlates with Survivin Splice Variant Expression and Improved Overall Survival

2010 ◽  
Vol 33 (5-6) ◽  
pp. 177-189 ◽  
Author(s):  
Anna G. Antonacopoulou ◽  
Konstantina Floratou ◽  
Vasiliki Bravou ◽  
Anastasia Kottorou ◽  
Fotinos-Ioannis Dimitrakopoulos ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Splice Variant ◽  
Splice Variants ◽  
Colorectal Carcinogenesis ◽  
Clinicopathological Parameters ◽  
Mrna Levels ◽  
Colorectal Carcinomas ◽  
Tissue Samples ◽  
Survivin Protein

Background: Survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386C/T and −31G/C polymorphisms were investigated.Methods: Quantitative RT-PCR was used to assess mRNA levels in fresh/frozen tissue samples. Protein levels were immunohistochemically evaluated on formalin-fixed paraffin-embedded tissue sections. Individuals were genotyped using real time PCR.Results: Expression of all 5 survivin splice variants as well as survivin protein was elevated in colorectal carcinomas compared to normal tissue. Specific splice variant expression differentially correlated with clinicopathological parameters. Furthermore, both snps correlated with splice variant levels or their ratios in colorectal carcinomas while the −31G/C snp may be related to CRC development and improved overall survival.Conclusion: Our results support a role of survivin in colorectal carcinogenesis while the −31G/C snp may constitute a marker of survival.

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