Increased ERCC Expression Correlates w ith Improved Outcome of Patients T reated w ith C isplatin as an A djuvant Therapy for Curatively Resected Gastric Cancer

Sun Kyung Baek,Si-Young Kim,이재진,Yoon Wha Kim,Hwi Joong Yoon,Kyung Sam Cho 대한암학회 2006 Cancer Research and Treatment Vol.38 No.1

Purpose: It has been reported that the overexpression of the excision repair cross-complementing 1 (ERCC1) gene, which is essential for the repair of cisplatin (CDDP)- DNA adducts, negatively influences the effectiveness of CDDP-based therapy for primary gastric cancer. We investigated whether the ERCC1 expression was associated with survival for gastric cancer patients in an adjuvant setting. Materials and Methods: We retrospectively analyzed 44 patients who were diagnosed with stage II or higher disease after undergoing curative resection and they had also received cisplatin-based chemotherapy. The ERCC1 expression was examined by performing immunohistochemical (IHC) staining, and this was divided into two groups according to the percentage of IHC staining of the tumor cell nuclei (negative: 10% or less, positive: more than 10%).Results: Among the 44 patients (ERCC1-negative/ERCC1-positive group=16/28), 32 patients were male and their median age was 52 years. There was no difference for the baseline characteristics of the two groups. The median follow-up duration was 41 months. The median disease-free survival (DFS) and the overall survival (OS) for the ERCC1-positive group were significant higher than those of the ERCC1-negative group (DFS: 40.4 vs. 14.6 months, p=0.02, OS: undefined vs. 20.4 months, p=0.008). Conclusion: The overall survival in gastric cancer patients who received cisplatin-based adjuvant chemotherapy after a curative resection is higher in those patients showing the overexpression of the ERCC1 gene. However, prospective studies using the ERCC1 gene expression as a prognostic marker for the DNA repair activity are needed. (Cancer Res Treat. 2006;38:19-24) Purpose: It has been reported that the overexpression of the excision repair cross-complementing 1 (ERCC1) gene, which is essential for the repair of cisplatin (CDDP)- DNA adducts, negatively influences the effectiveness of CDDP-based therapy for primary gastric cancer. We investigated whether the ERCC1 expression was associated with survival for gastric cancer patients in an adjuvant setting.Materials and Methods: We retrospectively analyzed 44 patients who were diagnosed with stage II or higher disease after undergoing curative resection and they had also received cisplatin-based chemotherapy. The ERCC1 expression was examined by performing immunohistochemical (IHC) staining, and this was divided into two groups according to the percentage of IHC staining of the tumor cell nuclei (negative: 10% or less, positive: more than 10%).Results: Among the 44 patients (ERCC1-negative/ERCC1-positive group=16/28), 32 patients were male and their median age was 52 years. There was no difference for the baseline characteristics of the two groups. The median follow-up duration was 41 months. The median disease-free survival (DFS) and the overall survival (OS) for the ERCC1-positive group were significant higher than those of the ERCC1-negative group (DFS: 40.4 vs. 14.6 months, p=0.02, OS: undefined vs. 20.4 months, p=0.008).Conclusion: The overall survival in gastric cancer patients who received cisplatin-based adjuvant chemotherapy after a curative resection is higher in those patients showing the overexpression of the ERCC1 gene. However, prospective studies using the ERCC1 gene expression as a prognostic marker for the DNA repair activity are needed. (Cancer Res Treat. 2006;38:19-24)

Combination of TRAP1 and ERCC1 Expression Predicts Clinical Outcomes in Metastatic Colorectal Cancer Treated with Oxaliplatin/5-Fluorouracil

한재준,백선경,이재진,김교영,김시영,이석환 대한암학회 2014 Cancer Research and Treatment Vol.46 No.1

PurposeThe novel heat shock protein tumor necrosis factor receptor-associated protein 1(TRAP1) is associated with multidrug resistance in colorectal cancer (CRC) cells invitro. Excision repair cross-complementation group 1 (ERCC1) expression levels intumor tissues also predict clinical outcomes in metastatic CRC patients receivingcombination oxaliplatin and 5-fluorouracil treatment. We investigated whether TRAP1and ERCC1 protein expression by immunohistochemistry predict clinical outcomes inCRC patients. Materials and MethodsThe study population consisted of 56 patients with metastatic CRC who receivedfirst-line oxaliplatin/5-fluorouracil therapy. Clinical response and overall survival (OS)by levels of the markers TRAP1 and ERCC1 were evaluated. ResultsThe rates of TRAP1 and ERCC1 expression were 21% and 52%, respectively. Patientsnegative for ERCC1 expression showed a tendency to respond to chemotherapy(p=0.066). Median OS was significantly longer in patients negative for TRAP1 thanthose positive for TRAP1 (p=0.023). Patients negative for ERCC1 expression also hada better OS than those positive for ERCC1 (p=0.021). The median OS was 30.9months for patients negative for TRAP1 and ERCC1 compared to 13.2 months forthose positive for TRAP1 and/or positive for ERCC1 expression (p=0.006). Thecombination of TRAP1 and ERCC1 expression was significantly associated with theresponse to chemotherapy (p=0.046) and independently predicted median OS inmultivariate analysis (hazard ratio, 2.98; 95% confidence interval, 1.18 to 7.49). ConclusionThe present study demonstrates that the combination of TRAP1 and ERCC1 expressionpredicts the survival of metastatic CRC patients who were treated with oxaliplatin/5-fluorouracil.

Expression of ERCC1, MSH2 and PARP1 in Non-small Cell Lung Cancer and Prognostic Value in Patients Treated with Platinum-based Chemotherapy

Xie, Ke-Jie,He, Hong-Er,Sun, Ai-Jing,Liu, Xi-Bo,Sun, Li-Ping,Dong, Xue-Jun Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.6

Purpose: To evaluate the prognostic value of the expression of excision repair cross-complementation group l (ERCC1), MutS protein homolog 2 (MSH2) and poly ADP-ribose polymerase 1 (PARP1) in non-small-cell lung cancer patients receiving platinum-based postoperative adjuvant chemotherapy. Methods: Immunohistochemistry was applied to detect the expression of ERCC1, MSH2 and PARP1 in 111 cases of non-small cell lung cancer paraffin embedded surgical specimens. Through og-rank survival analysis, we evaluated the prognostic value of the ERCC1, MSH2, PARP1 and the related clinicopathological factors. COX regression analysis was used to determine whether ERCC1, MSH2 and PARP1 were independent prognostic factors. Results: In the enrolled 111 non-small cell lung cancer patients, the positive expression rate of ERCC1, MSH2 and RARP1 was 33.3%, 36.9% and 55.9%, respectively. ERCC1 (P<0.001) and PARP1 (P=0.033) were found to be correlated with the survival time while there was no correlation for MSH2 (P=0.298). Patients with both ERCC1 and PARP1 negative cancer had significantly longer survival time than those with ERCC1 (P=0.042) or PARP1 (P=0.027) positive alone. Similalry, the survival time of patients with both ERCC1 and PARP1 positive cancer was shorter than those with ERCC1 (P=0.048) or PARP1 (P=0.01) positive alone. Conclusion: Patients with ERCC1 or PARP1 negative non-small cell lung cancer appear to benefit from platinum-based postoperative adjuvant chemotherapy.

GSTP1, ERCC1 and ERCC2 Polymorphisms, Expression and Clinical Outcome of Oxaliplatin-based Adjuvant Chemotherapy in Colorectal Cancer in Chinese Population

Li, Hui-Yan,Ge, Xin,Huang, Guang-Ming,Li, Kai-Yu,Zhao, Jing-Quan,Yu, Xi-Miao,Bi, Wen-Si,Wang, Yu-Lin Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

Aim: Platinum agents have shown to be effective in the treatment of colorectal cancer. We assessed whether single nucleotide polymorphisms (SNPs) in GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln might predict the overall survival in patients receiving oxaliplatin-based chemotherapy in a Chinese population. Methods: SNPs of GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln in 335 colorectal cancer patients were assessed using TaqMan nuclease assays. Results: At the time of final analysis on Nov. 2011, the median follow-up period was 37.7 months (range from 1 to 60 months). A total of 229 patients died during follow-up. Our study showed GSTP1 Val/Val (HR=0.44, 95% CI=0.18-0.98), ERCC1 C/C (HR=0.20, 95% CI=0.10-0.79) and ERCC2 G/G (HR=0.48, 95% CI=0.19-0.97) to be significantly associated with better survival of colorectal cancer. GSTP1 Val/Val, ERCC1 C/C and ERCC2 G/G were also related to longer survival among patients with colon cancer, with HRs (95% CIs) of 0.41 (0.16-0.91), 0.16 (0.09-0.74) and 0.34 (0.16-0.91), respectively. Conclusion: GSTP1, GSTP1, ERCC1 Asn118Asn and ERCC2 Lys751Gln genotyping might facilitate tailored oxaliplatin-based chemotherapy for colorectal cancer patients.

ERCC1 as a Biological Marker Guiding Management in Malignant Pleural Mesothelioma

Cihan, Yasemin Benderli,Ozturk, Ahmet,Arslan, Alaettin,Deniz, Kemal,Baran, Munevver,Karaca, Halit Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.10

Background: To determine prognostic value of excision repair cross-complementation 1 (ERCC1) in patients with malignant pleural mesothelioma (MPM). Materials and Methods: The study included 60 patients with MPM who were diagnosed and treated in the Radiation Oncology Department of Kayseri Teaching Hospital and Medical Oncology Department of Erciyes University, Medicine School between 2005 and 2013. By using immunohistochemical methods, ERCC1 expression in biopsy specimens was evaluated. We retrospectively assessed whether there is a correlation between ERCC1 and response to anti-neoplastic therapy or survival. Results: There were 50 men and 10 women with median age of 62 years (range: 39-83). Histological type was epithelial mesothelioma in the majority of the cases (85%), most commonly presenting in stage four. Of the cases, 20 (33%) received radiotherapy, 60 (%100) received first-line chemotherapy and 15 (%25) received second-line chemotherapy. In the assessment after therapy, it was found that there was partial response in 12 cases (20%), stable disease in 19 cases (31.4%) and progression in 25 cases (41.7%). ERCC1 was positive in 43% of the cases. Mean OS was 11.7 months and mean DFS was 9.5 months in ERCC1-positive cases regardless of therapy, while they were 19.2 months and 17.1 months in ERCC1-negative cases, respectively. The difference was found to be significant (p<0.05). In univariate analysis, stage, comorbidity, response to treatment and ERCC1 expression were found to be significantly associated with OS (p=0.083; p=0.043; p=0.041; p=0.050). In multivariate analysis, response to treatment remained to be significant for OS (p=0.005). In univariate and multivariate analyses, response to treatment and ERCC1 were found to be significantly associated with DFS (p=0.049; p=0.041). Conclusions: ERCC1 was identified as poor prognostic factor in patients with MPM.

Association of Four ERCC1 and ERCC2 SNPs with Survival of Bone Tumour Patients

Hao, Ting,Feng, Wei,Zhang, Jie,Sun, Yong-Jian,Wang, Gang Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.8

Aim: SNPs of ERCC1 and ERCC2 genes have been found to be associated with response to platinum therapy in different clinical settings. In the current study, we investigated the relationship of SNPs in ERCC1 and ERCC2 to cisplain response and survival in osteosarcoma patients. Methods: 267 consecutive patients diagnosed with osteosarcoma between January 2003 to January 2005 were followed up until the end of January 2010. ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln polymorphisms were detected based upon the Sequenom MassARRAY platform.Results: For ERCC1 Asn118Asn, the variant genotype T/T was strongly significantly associated with a higher event free survival when compared with the wild-type C/C, with an adjusted OR (95% CI) of 0.39 (0.14-0.95). ERCC2 751 A/A genotype showed increased event free survival of osteosarcoma (HR=0.44; 95%CI=0.10-0.87). However, we did not find significant association of ERCC1 Gln504Lys and ERCC2 Asp312Asn polymorphisms with prognosis of osteosarcoma. Conclusions: We first report associations of four SNPs, ERCC1 Asn118Asn, ERCC1 Gln504Lys, ERCC2 Asp312Asn and ERCC2 Lys751Gln, with risk of death from osteosarcoma in a Chinese population, indicating ERCC1 118T/T and ERCC2 A/A may be used as surrogate markers for clinical outcome of osteosarcoma treatmetn with cisplain.

Predictive Value of the ERCC1 Expression for Treatment Response and Survival in Advanced Gastric Cancer Patients Receiving Cisplatin-based First-line Chemotherapy

윤진아,김경미,김승태,김정훈,김정아,공지현,이수현,원영웅,선종무,이지연,박세훈,박준오,박영석,임호영,강원기 대한암학회 2010 Cancer Research and Treatment Vol.42 No.2

Purpose The aim of this study was to determine whether the ERCC1 expression is effective to predict the clinical outcomes of patients with advanced gastric cancer (AGC) and who were treated with cisplatin-based first-line chemotherapy. Materials and Methods A total of 89 measurable AGC patients received cisplatin and capecitabine, with or without epirubicin, as a part of a randomized phase II study. Patients were included for the current molecular analysis if they had received two or more cycles of chemotherapy, their objective tumor responses were measured and if their paraffin-embedded tumor samples were available. The ERCC1 expression was examined by performing immunohistochemical (IHC) staining, and the patients were divided into two groups (positive or negative) according to the presence of IHC staining of the tumor cell nuclei. Results Of the 32 eligible patients, 21 patients (66%) had tumor with a positive expression of ERCC1 and the remaining 11 patients had tumor with a negative ERCC1-expression. The ERCC1- negative patients achieved a higher response rate than that of the ERCC1-positive patients (44% vs. 28%, respectively), although the difference was not statistically significant (p=0.42). The median survival time for the all patients was 14.6 months (95% CI: 13.6 to 15.6 months). The one-year survival rate was similar for the ERCC1-negative patients (61%) and the ERCC-1-positive patients (70%). Conclusion In the current study, the tumor ERCC1 expression by IHC staining could not predict the clinical response or survival of AGC patients who were treated with cisplatin-based first-line chemotherapy. The ERCC1 protein expression does not appear to be a useful tool for the selection of tailored chemotherapy for these patients.

Prognostic implication of ERCC1 protein expression in resected oropharynx and oral cavity cancer

An, H.J.,Jo, H.,Jung, C.K.,Kang, J.H.,Kim, M.S.,Sun, D.I.,Cho, K.J.,Cho, J.H.,Won, H.S.,Sun, D.S.,Ko, Y.H. G. Fischer 2017 Pathology, research and practice Vol.213 No.8

Background: Excision repair cross complement group 1 (ERCC1) expression is a predictive biomarker for platinum-containing treatment in squamous cell carcinoma of head and neck (SCCHN). However, the prognostic significance after surgical resection is not well understood. Methods: Oropharynx (n=143) or oral cavity (n=61) SCCHN patients undergoing surgery were included. ERCC1 protein expression and HPV status were assessed by ERCC1 and p16 immunohistochemistry. Results: The ERCC1, over-expressed in 66.7% of patients, was associated with oral cavity cancer (P<0.001), well differentiation (P=0.036), and HPV negativity (P<0.001). In TCGA database, ERCC1 mRNA upregulation was enriched in HPV-negative and oral cavity cancers, and associated with HRAS mutation (P<0.001). The prognostic role of ERCC1 was not different according to HPV status. High ERCC1 expression showed a trend toward poor prognosis in patients with an advanced stage (P=0.079) with marginal significance. Conclusions: The ERCC1 expression was not prognostic in surgically resected oropharynx/oral cavity SCCHN, irrespective of HPV status. However, it could provide additional prognostic information for advanced stage patients.

The Expression of ERCC1, RRM1, and BRCA1 in Breast Cancer According to the Immunohistochemical Phenotypes

김도경,정우희,구자승 대한의학회 2011 Journal of Korean medical science Vol.26 No.3

We studied the expression of BRCA1, ERCC1, and RRM1 which play an important role in DNA repair systems in breast cancer. Immunohistochemical staining for EGFR, BRCA1,ERCC1, and RRM1 were performed by using a tissue microarray made from 230 breast cancer patients. Patients were classified into luminal A, luminal B, HER-2, and triple negative breast cancer (TNBC) types according to ER, PR, and HER-2 expression. The expression of ERCC1, RRM1, and BRCA1 were correlated (P < 0.05). The expression level of ERCC1 was the lowest in TNBC type (P = 0.031), ERCC1 negativity was more prominent in TNBC and luminal B groups than luminal A and HER-2 groups (P = 0.013). Cases with EGFR overexpression showed high expression of RRM1 and BRCA1 (P = 0.046, and 0.004,respectively). In conclusion, the expression of ERCC1 is particularly lower in TNBCs than other types of breast cancers.

The ERCC1 C118T Polymorphism Predicts Clinical Outcomes of Colorectal Cancer Patients Receiving Oxaliplatin-Based Chemotherapy: a Meta-analysis Based on 22 Studies

Qian, Ying-Ying,Liu, Xin-You,Wu, Qian,Song, Xian,Chen, Xiao-Feng,Liu, Yi-Qian,Pei, Dong,Shen, Li-Zong,Shu, Yong-Qian Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.19

Background: Although the predictive value of the excision repair cross-complementing group 1 (ERCC1) C118T polymorphism in clinical outcomes of patients with colorectal cancer (CRC) receiving oxaliplatin-based chemotherapy has been evaluated in numerous published studies, the conclusions are conflicting. Therefore, we performed the present meta-analysis to determine the precise role of the ERCC1 C118T polymorphism in this clinical situation and help optimize individual chemotherapy. Materials and Methods: A multiple search strategy was used to identify eligible studies. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were used to estimate objective response and oxaliplatin-induced toxicity, with hazard ratios (HRs) with 95%CIs for progression-free survival (PFS) and overall survival (OS). Results: A total of 22 studies including 2,846 CRC patients were eligible in the analysis. Overall, no significant correlation was found between the ERCC1 C118T polymorphism and objective response to oxaliplatin-based chemotherapy, in all patients or in the Asian and Caucasian subgroups. However, the pooled analysis showed that the PFS and OS were significantly shorter in patients who carried T/T or T/C genotypes of ERCC1 C118T as compared to the C/C genotype. On stratified analysis by ethnicity, the ERCC1 118T allele was associated with a favorable prognosis in Caucasians (PFS, HR=0.58, 95%CI: 0.24-1.44; OS, HR=0.38, 95%CI: 0.22-0.64) but an unfavorable prognosis in Asians (PFS, HR=2.49, 95%CI: 1.87-3.33; OS, HR=2.63, 95%CI: 1.87-3.69) based on a dominant model. In addition, we failed to find a statistically significant impact of ERCC1 C118T polymorphism on oxaliplatin-induced toxicity. Conclusions: The ERCC1 C118T polymorphism may have prognostic value in patients with CRC undergoing oxaliplatin-based chemotherapy.