Prognostic significance of thymidylate synthase polymorphisms in rectal cancer patients treated with neoadjuvant chemoradiotherapy

2013 ◽  
Vol 15 (4) ◽  
pp. 428-435 ◽  
Author(s):  
V. Arrazubi ◽  
J. Suárez ◽  
D. Guerrero ◽  
M. Gómez ◽  
A. Viúdez ◽  
...  
In Vivo ◽  
2019 ◽  
Vol 33 (6) ◽  
pp. 1959-1965 ◽  
Author(s):  
HEE JEONG CHO ◽  
JIN HO BAEK ◽  
DONG WON BAEK ◽  
BYUNG WOOG KANG ◽  
SOO JUNG LEE ◽  
...  

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 435-435
Author(s):  
L. Conradi ◽  
A. Bleckmann ◽  
M. Schirmer ◽  
T. Sprenger ◽  
K. Homayounfar ◽  
...  

435 Background: Fluorouracil (5FU) remains the backbone of neoadjuvant radiochemotherapy (RCT) as well as adjuvant therapeutic strategies in multimodal treatment of rectal cancer patients. Due to its central role as the major target of 5FU thymidylate synthase (TS) is a promising biomarker in rectal cancer. We assessed TS in 208 patients with regard to its predictive/prognostic capacity for disease free DFS and overall cancer specific survival (CSS). Methods: 167 patients cUICC stages II (28%) and III (72%) received preoperative 5FU based RCT followed by total mesorectal excision (TME) A comparison group n = 41 received postoperative RCT after primary TME. All patients were treated after standardized protocols within phase-II/-III trials of the German Rectal Cancer Study Group. TS levels from pretreatment biopsies and corresponding resection specimens were assessed by immunohistochemical staining for their impact on DFS and CSS. Additionally, a TS gene polymorphism (28 bp repeat) was analysed in respect to intracellular protein expression levels and prognostic significance. Results: Patients with low TS expression in pre-treatment biopsies showed a correlation with impaired CSS (p = 0.015). After neoadjuvant RCT there was evidence of lymph node metastases ypUICC stage III in 32.6%. Complete histopathologically confirmed tumor regression TRG 4 was achieved in 16 patients (9.5%). During follow-up (median 57 months) patients with low intratumoral TS expression and positive nodal status were at high risk for local and/or distant metastatic recurrence (p = 0.040). Analysis of the 28bp repeat revealed a correlation of *3/*3 genotype with high TS expression in pretherapeutical biopsies (p = 0.05). Conclusions: TS represents a prognostic biomarker in locally advanced rectal cancer indicating an unfavourable outcome for patients with low TS expression and might help to adapt adjuvant therapy regimens by stratifying patients according to their risk for cancer recurrence. No significant financial relationships to disclose.


BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Iryna Trotsyuk ◽  
Halina Sparschuh ◽  
Alice Josephine Müller ◽  
Konrad Neumann ◽  
Martin Kruschewski ◽  
...  

Abstract Background Budding is a complementary prognostic factor for colorectal cancer. In this study, we aimed to clarify the role of tumor budding in rectal cancer patients after preoperative chemoradiotherapy. Methods A total of 124 patients with rectal cancer treated with neoadjuvant chemoradiotherapy and consecutive surgery were included. Surgical specimens were evaluated for budding and routine clinicopathological features. Budding was evaluated on hematoxylin and eosin (H&E)-stained slides and by cytokeratin immunohistochemical (IHC) staining. Results A budding rate of 36.9% (n = 38) by H&E and 55.6% (n = 55) by IHC was observed. Budding was significantly associated with a high ypT and ypN status, poor differentiation, and low degrees of tumor regression. Moreover, budding was strongly predictive of a worse patient outcome, as measured by tumor recurrence or death. In multivariate analyses, budding remained the only significant parameter for overall survival and was even superior to the ypT and ypN status (budding in H&E: hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.15–6.44, p = 0.023; budding in IHC: HR 5.19, 95% CI 1.62–16.61, p = 0.006). Conclusion Budding is a strong prognostic predictor of survival in rectal cancer patients after neoadjuvant therapy. A standardized evaluation of tumor budding after neoadjuvant therapy may thus aid in risk stratification and guide the clinical management of patients with rectal cancer. Immunostaining can help to enhance the diagnostic accuracy and prognostic significance.


2010 ◽  
Vol 136 (11) ◽  
pp. 1681-1689 ◽  
Author(s):  
David Páez ◽  
Laia Paré ◽  
Albert Altés ◽  
Francesc Josep Sancho-Poch ◽  
Lourdes Petriz ◽  
...  

Onkologie ◽  
2016 ◽  
Vol 10 (5) ◽  
pp. 228-230
Author(s):  
David Buka ◽  
Josef Dvořák ◽  
Veronika Sitorová ◽  
Igor Richter ◽  
Igor Sirák ◽  
...  

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