scholarly journals GNAS1 T393C polymorphism is associated with histopathological response to neoadjuvant radiochemotherapy in esophageal cancer

2009 ◽  
Vol 9 (3) ◽  
pp. 202-207 ◽  
Author(s):  
H Alakus ◽  
U Warnecke-Eberz ◽  
E Bollschweiler ◽  
S P Mönig ◽  
D Vallböhmer ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Neoadjuvant Radiochemotherapy ◽  
Histopathological Response ◽  
Gnas1 T393c

Survivin expression in esophageal cancer: Association with histomorphological response to neoadjuvant therapy and prognosis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4536-4536 ◽  
Author(s):  
D. Vallboehmer ◽  
E. Kuhn ◽  
J. Brabender ◽  
R. Metzger ◽  
U. Warnecke-Eberz ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Protein Expression ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Survivin Expression ◽  
Neoadjuvant Radiochemotherapy ◽  
Advanced Esophageal Cancer ◽  
Survivin Protein ◽  
Histopathologic Response ◽  
Locally Advanced Esophageal Cancer

4536 Background: The poor prognosis associated with locally advanced esophageal cancer prompted an evaluation of combined modality treatments including neoadjuvant radiochemotherapy in combination with surgery. However, it has been well established that only patients with a complete pathological response to neoadjuvant therapy will have a significant survival benefit. Therefore, predictive markers to allow a tailored radiochemotherapy are needed. The aim of this study was to examine the association of the protein expression of survivin, an inhibitor of apoptosis, with histopathologic response to neoadjuvant radiochemotherapy and prognosis of patients with locally-advanced esophageal cancer. Methods: 59 patients with esophageal cancer (cT2–4, Nx, M0) received neoadjuvant radiochemotherapy (cisplatin, 5-FU, 36 Gy) followed by esophagectomy. Histomorphologic regression was defined as major response when resected specimens contained less than 10 % and as minor response when resected specimens contained more than 10 % of residual vital tumor cells. Pre- and post-therapeutic intratumoral protein expression of survivin was determined and correlated with clinicopathologic parameters. Results: The pre-therapeutic intratumoral survivin protein expression was not associated with any clinicopathologic factor, including histopathologic response and prognosis. Survivin protein expression was significantly reduced during neoadjuvant therapy, showing lower levels in post-therapeutic tumor samples (p<0.01). Higher postoperative survivin levels were significantly associated with a higher ypT-stage (p<0.009), a poorer histopathologic response (p<0.01) and a shorter overall survival (p<0.028). Conclusions: The intratumoral protein expression of survivin was significantly down-regulated during neoadjuvant therapy, whereas a higher survivin level after pre-operative therapy was significantly associated with a worse histopathologic response and prognosis. Therapeutic strategies which are able to reduce survivin expression or to block survivin mediated pathways might increase the histopathologic response rate and prognosis in the multimodal therapy of patients with locally-advanced esophageal cancer. No significant financial relationships to disclose.

T1908 Gene Polymorphisms of ERCC1 Predict Response to Neoadjuvant Radiochemotherapy in Esophageal Cancer

2008 ◽  
Vol 134 (4) ◽  
pp. A-893
Author(s):  
Ralf Metzger ◽  
Ute Warnecke-Eberz ◽  
Elfriede Bollschweiler ◽  
Daniel Vallbohmer ◽  
Jan Brabender ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Gene Polymorphisms ◽  
Neoadjuvant Radiochemotherapy

XPA and XRCC3 gene polymorphisms and survival in esophageal cancer patients receiving neoadjuvant radiochemotherapy with cisplatin (CDDP), docetaxel (DTX), and 5-fluorouracil (FU)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14571-e14571 ◽  
Author(s):  
M. Gusella ◽  
G. De Manzoni ◽  
R. Marinelli ◽  
S. Bruscagin ◽  
A. Bononi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Patients ◽  
Gene Polymorphisms ◽  
Locally Advanced ◽  
Pathological Response ◽  
Rank Test ◽  
Neoadjuvant Radiochemotherapy ◽  
Risk Of Death ◽  
Increased Risk ◽  
Xrcc3 Gene

e14571 Background: The aim of the study was to evaluate if genetic polymorphism of DNA repair genes may predict pathological response and survival in patients affected by locally advanced esophageal cancer, treated with a neoadjuvant schedule including weekly DTX (35 mg/mq) and CDDP (25mg/mq), protracted venous infusion of FU (150 mg/mq/die) and concomitant radiotherapy for 8 weeks followed by surgery. Methods: Fifty-seven patients were enrolled, aged 60±7 years old. Median follow-up was 27 months. Genomic DNA was extracted from peripheral blood lymphocytes and XPA, XPD, XRCC1, ERCC1 and XRCC3 were genotyped through RFLP analysis. Associations between gene polymorphisms and pathological response and survival were analysed through Chi square test and Log rank test respectively. Results: Thirty-two patients presented complete remission (pCR) and 10 patients microfocal residual disease (pMRD); the remaining 15 patients were considered stable or non-responders (pS-NR). The event free(EFS) and overall (OS) median survival times have not yet reached; significantly better 3-year survival rates were observed after pCR than in case of pMRD and pS-NR (EFS: 87% vs 42.8%, p=0.0004; OS: 86% vs 56%, p=0.02, respectively). No association was found between pathological response or survival with XRCC1, ERCC1 and XPD polymorphisms. On the contrary, the XPA 23AA genotype showed an increased risk of recurrence (HR=3.5; 95% CI 1.3 to 43.7, p=0.02) and death (HR=4.4, 95% CI 1.9 to 78.2, p=0.009); there was a trend for reduced risk of negative pathological response with decreasing number of allele 23A : MRD and S-NR were found in 71%, 45% and 35% cases for AA, AG and GG genotypes, respectively. The XRCC3 241MetMet variant was significantly associated with increased risk of death (HR= 6.0, 95% CI 3.0 to 40.0, p=0.008); a trend toward a higher recurrence (p=0.07) and worse response (60% vs 43%) was found. Conclusions: XPA and XRCC3 gene defective variants were significantly associated with worse outcome and could predict OS in esophageal cancer patients treated with a neo-adjuvant intensive radio-chemotherapy protocol. Founded by CARIPARO, Italy No significant financial relationships to disclose.

Quantitative analysis ofSurvivinRNA expression in blood as a non-invasive predictor of response to neoadjuvant radiochemotherapy in esophageal cancer

2009 ◽  
Vol 100 (6) ◽  
pp. 447-451 ◽  
Author(s):  
Peter Grimminger ◽  
Daniel Vallböhmer ◽  
Andreas Hoffmann ◽  
Christian Schulte ◽  
Elfriede Bollschweiler ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Quantitative Analysis ◽  
Neoadjuvant Radiochemotherapy ◽  
Non Invasive

Abstract 1167: The GNAS1 T393C polymorphism is a predictor of clinical outcome in esophageal cancer

2010 ◽  
Author(s):  
Katharina E. Effenberger ◽  
Safije Musici ◽  
Emre F. Yekebas ◽  
Asad Kutup ◽  
Till Kamradt ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Clinical Outcome ◽  
Gnas1 T393c
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