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Integrating TYMS, KRAS and BRAF testing in patients with metastatic colorectal cancer

World Journal of gastroenterology 2017年第32期23卷 5913-5924页

作者： Anastasios Ntavatzikos Aris Spathis Paul Patapis Nikolaos Machairas george Peros Stefanos Konstantoudakis Danai Leventakou ioannis g panayiotides Petros Karakitsos Anna Koumarianou Hematology-Oncology Unit 4^th Department of Internal MedicineMedical SchoolNational and Kapodistrian University of Athens“ATTIKON”University Hospital Department of Cytopathology National and Kapodistrian University of AthensMedical School“ATTIKON”University Hospital 3^rd Department of Surgery Medical SchoolNational and Kapodistrian University of Athens“ATTIKON”University Hospital Department of Surgery Medical SchoolNational and Kapodistrian University of AthensEvgenideio Therapeutirio S.A.“I AGIA TRIAS”11528 AthensGreece 2^nd Department of Pathology University of AthensMedical School“ATTIKON”University Hospital

AIM To investigate the impact of thymidylate synthase(TYMS), KRAS and BRAF in the survival of metastatic colorectal cancer(m CRC) patients treated with chemotherapy. METHODS Clinical data were collected retrospectively from records of consecutive patients with m CRC treated with fluoropyrimidine-based chemotherapy from 1/2005 to 1/2007. Formalin-fixed paraffin-embedded tissues were retrieved for analysis. TYMS genotypes were identified with restriction fragment analysis PCR, while KRAS and BRAF mutation status was evaluated using real-time PCR assays. TYMS gene polymorphisms of each of the 3' untranslated region(UTR) and 5'UTR were classified into three groups according to the probability they have for high, medium and low TYMS expression(and similar levels of risk) based on evidence from previous studies. Univariate and multivariate survival analyses were *** The analysis recovered 89 patients with m CRC(46.1% de novo metastatic disease and 53.9% relapsed). Of these, 46 patients(51.7%) had colon cancer and 43(48.3%) rectal cancer as primary. All patients were treated with fluoropyrimidine-based chemotherapy(5FU or capecitabine) as single-agent or in combination with irinotecan or/and oxaliplatin or/and bevacizumab. With a median follow-up time of 14.8 mo(range 0-119.8), 85 patients(95.5%) experienced disease progression, and 63 deaths(70.8%) were recorded. The 3-year and 5-year OS rate was 25.4% and 7.7% while the 3-year progression-free survival rate was 7.1%. Multivariate analysis of TYMS polymorphisms, KRAS and BRAF with clinicopathological parameters indicated that TYMS 3'UTR polymorphisms are associated with risk for disease progression and death(P genotypes ins/ins and ins/loss of heterozygosity(LOH) linked with high TYMS expression) tumors with del/del genotype(low expression group) and tumors with ins/del or del/LOH(intermediate expression group) have lower risk

关键词： Thymidylate synthase Polymorphisms m CRC Loss of heterozygosity Survival Chemotherapy KRAS BRAF TYMS

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Simultaneous occurrence of colonic adenocarcinoma and MALT lymphoma:A series of three cases

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World Journal of gastrointestinal Oncology 2012年第4期4卷 89-93页

作者： Theodoros Argyropoulos Periklis Foukas Maria Kefala Panagiotis Xylardistos Sotirios Papageorgiou Nikolaos Machairas Evmorfia Boltetsou Anastasios Machairas ioannis g panayiotides 2nd Department of Pathology University of Athens Medical School'Attikon' University HospitalRimini1GR-12464ChaidariGreece 3rd Department of Surgery University of Athens Medical School'Attikon' University HospitalRimini1GR-12464ChaidariGreece Haematology Unit 2nd Department of Internal Medicine-PropaedeuticUniversity of Athens Medical School'Attikon' University HospitalRimini1GR-12464ChaidariGreece

Simultaneous development of adenocarcinoma and primary B cell lymphoma of mucosa-associated lymphoid tissue(MALT) lymphoma of the colon is rare;only one case has so far been reported out of 13 cases with the coexistence of colonic adenocarcinoma with involvement of the colon by *** hereby present three more cases,two females(aged 75 and 71 years) and a male(aged 72 years).All three underwent colectomy based on a preoperative biopsy revealing colonic *** examination of the resection specimens disclosed a colonic adenocarcinoma in two cases,whereas a tubulovillous adenoma with superficial foci of intraepithelial adenocarcinoma was seen in the ***,in all three cases,a coexisting MALT lymphoma was diagnosed in the colon(1 case),in both colon and adjacent lymph nodes(1 case) or in colonic lymph nodes and omentum(1 case).In the last case,a post-operative bone marrow biopsy revealed extensive infiltration of the bone marrow,due to which the patient received postoperative *** and treatment issues are briefly discussed.

关键词： Colon Adenocarcinoma B cell lymphoma of mucosa-associated lymphoid tissue lymphoma

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TYMS/KRAS/BRAF molecular profiling predicts survival following adjuvant chemotherapy in colorectal cancer

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World Journal of gastrointestinal Oncology 2019年第7期11卷 551-566页

作者： Anastasios Ntavatzikos Aris Spathis Paul Patapis Nikolaos Machairas georgia Vourli george Peros Iordanis Papadopoulos ioannis panayiotides Anna Koumarianou Hematology-Oncology Unit 4th Department of Internal Medicine Medical School National and Kapodistrian University of Athens“ATTIKON” University Hospital Athens 12462 Greece Department of Cytopathology National and Kapodistrian University of Athens Medical School“ATTIKON” University Hospital Athens 12462 Greece 3rd Department of Surgery Medical School National and Kapodistrian University of Athens“ATTIKON” University Hospital Athens 12462 Greece Department of Hygiene Epidemiology and Medical Statistics Medical School National and Kapodistrian University of Athens Athens 11527 Greece Department of Surgery Medical School National and Kapodistrian University of Athens Evgenideio Therapeutirio S.A.“I AGIA TRIAS” Athens 11528 Greece 2nd Department of Pathology University of Athens Medical School“ATTIKON” University Hospital Athens 12462 Greece

BACKgROUND Patients with stage II-III colorectal cancer (CRC) treated with adjuvant chemotherapy, gain a 25% survival benefit. In the context of personalized medicine, there is a need to identify patients with CRC who may benefit from adjuvant chemotherapy. Molecular profiling could guide treatment decisions in these patients. Thymidylate synthase (TYMS) gene polymorphisms, KRAS and BRAF could be included in the molecular profile under consideration. AIM To investigate the association of TYMS gene polymorphisms, KRAS and BRAF mutations with survival of CRC patients treated with *** A retrospective study studied formalin-fixed paraffin-embedded tissues (FFPEs) of consecutive patients treated with adjuvant chemotherapy during January/2005-January/2007. FFPEs were analysed with PCR for the detection of TYMS polymorphisms, mutated KRAS (mKRAS) and BRAF (mBRAF). Patients were classified into three groups (high, medium and low risk) according to 5’UTR TYMS polymorphisms Similarly, based on 3’UTR polymorphism ins/loss of heterozygosity (LOH) patients were allocated into two groups (high and low risk of relapse, respectively). Cox regression models examined the associated 5- year survival outcomes. RESULTS One hundred and thirty patients with early stage CRC (stage I-II: 55 patients;stage III 75 patients;colon: 70 patients;rectal: 60 patients) were treated with surgery and chemotherapy. The 5-year disease free survival and overall survival rate was 61.6% and 73.9% respectively. 5’UTR polymorphisms of intermediate TYMS polymorphisms (2Rg/3Rg, 2Rg/LOH, 3RC/LOH) were associated with lower risk for relapse [hazard ratio (HR) 0.320, P = 0.02 and HR 0.343, P = 0.013 respectively] and death (HR 0.368, P = 0.031 and HR 0.394, P = 0.029 respectively). The 3’UTR polymorphism ins/LOH was independently associated with increased risk for disease recurrence (P = 0.001) and death (P = 0.005). mBRAF (3.8% of patients) was associated with increased risk of death (HR 4.500,

关键词： Colorectal neoplasms Thymidylate synthase Untranslated regions Fluorouracil KRAS BRAF Prognosis

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Human epidermal growth factor receptor-2 gene amplification in gastric cancer using tissue microarray technology

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World Journal of gastroenterology 2012年第2期18卷 150-155页

作者： Dimitrios Tsapralis ioannis panayiotides george Peros Theodore Liakakos Eva Karamitopoulou 3rd Department of Surgery Attikon University HospitalUniversity of AthensRimini 112464 AthensGreece 2nd Department of Pathology University of AthensRimini 112464 AthensGreece 4th Department of Surgery Attikon University HospitalUniversity of AthensRimini 112464 AthensGreece Department of Pathology Aretaieion University HospitalUniversity of AthensVass.Sophias 7611528 AthensGreece

AIM:To assess human epidermal growth factor receptor-2 (HER2)-status in gastric cancer and matched lymph node metastases by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH).METHODS:120 cases of primary gastric carcinomas and 45 matched lymph node metastases from patients with full clinicopathological features were mounted onto multiple-punch and single-punch tissue microarrays,respectively,and examined for HER2 overexpression and gene amplification by IHC and ***:Twenty-four tumors (20%) expressed HER2 *** IHC score of ≥ 2+ was observed in 20 tumors (16.6%).HER2 amplification was detected by CISH in 19 tumors (15.8%) and in their matched lymph node metastases.A high concordancerate was found between HER2 positivity (as detected by IHC) and HER2 gene amplification (as detected by CISH),since 19 of the 20 IHC positive cases were amplified (95%).All amplified cases had 2+ or 3+ IHC *** was associated with intestinal phenotype (P grading,staging or survival was ***:In gastric cancer,HER2 amplification is the main mechanism for HER2 protein overexpression and is preserved in lymph node metastases.

关键词： Human epidermal growth factor receptor-2 Immunohistochemistry Chromogenic in situ hybridiza-tion gastric cancer

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