High Excision Repair Cross-complementing Gene-1 Research Articles

Relationship between Expression of ERCC1 and Effect of Cisplatin Concurrent Chemoradiation in Stage II-IIIA Nasopharyngeal Carcinoma

To investigate the relationship between the expression of excision repair cross-complementing gene 1 (ERCC1) mRNA and protein and the effect of cisplatin concurrent chemoradiation (CCRT) in patients with stage II-IIIA nasopharyngeal carcinoma (NPC). From June 2012 to June 2015, 78 patients with histologically diagnosed stage II-IIIA NPC (7th AJCC stage) were recruited. Immunohistoehemistry and RT-PCR methods were used to detect the expression of ERCC1 protein and mRNA in tumor tissues of these patients before CCRT and correlate with treatment outcomes. The primary endpoints included tumor response by RECIST 1.1 criteria and overall survival (OS). Survivals were calculated with Kaplan-Meier method. The differences between survivals were calculated by Log-rank test. The differences between groups were analyzed using the χ2 test. All statistical tests were two-side. Of 78 patients, 36 patients were positive in expression of ERCC1 protein (46.15%). The expression of ERCC1 protein was not associated with gender, age, T stage and N stage (p>0.05). There were 63 patients with complete response (CR), 7 with partial response (PR), 4 with stable disease (SD), and 4 with disease progression (PD). In 42 patients with negative ERCC1 expression, 41 had CR and PR (97.62%). In comparison, only 29/36 (80.56%) patients with positive ERCC1 protein achieved CR and PR (p=0.036). The expression of ERCC1 mRNA ranged from 0.456 to 1.412 (median 1.119), which was not associated with gender, age, T stage, and N stage (p>0.05). Patients with low ERCC1 mRNA expression (< median) had higher CR and PR (40/41 versus 30/37 for high expression, p=0.043). The 5-year OS for all patients was 91.03%. The 5-year OS for those with negative ERCC1 protein expression was 92.86% versus 88.98% for those with positive ERCC1 protein (p=0.831). The 5-year OS for those with low ERCC1 mRNA expression was 92.68% versus 89.19% for those with high ERCC1 mRNA expression (p=0.887). The expression of ERCC1 protein and mRNA correlated with poorer response to concurrent cisplatin chemoradiation in stage II-IIIA NPC. They were not correlated with 5-year OS possible due to small patient sample size and excellent treatment outcomes of these patients.

A molecular biomarker targeted approach to adjuvant therapy for resected pancreatic adenocarcinoma: Results of a phase II prospective trial.

230 Background: Standard adjuvant treatment for resected pancreatic adenocarcinoma is gemcitabine (Gem) (CONKO-001 trial: Gem vs placebo DFS 13.4 vs 6.7 mo; p&lt;0.001; OS 22.8 vs 20.2 mo; p=0.01). Adding cisplatin (Cis) to Gem has shown increased response rates in the metastatic setting. This benefit may be inhibited by high expression of excision repair cross-complementing gene–1 (ERCC1), the key enzyme in nucleotide excision repair. This Phase II prospective trial assesses outcomes of patients treated with adjuvant Gem/Cis chemotherapy, stratifying results by tumor ERCC1 expression. Methods: Patients with resected pancreatic adenocarcinoma at a single institution were enrolled from 2010-2013. Initially, patients received Gem (1000 mg/m2) / Cis (50 mg/m2) Day 1/8/15, Q28d for 6 cycles. After enrolling 5 pts, this was modified to Day 1/15 due to toxicity. Two dose reductions were permitted. Intent to treat analyses were conducted. Tumor ERCC1 expression was evaluated by immunohistochemistry and dichotomized into low and high expression groups. Primary outcomes were RFS and OS stratified by ERCC1 expression. Results: Of 22 pts, 16 (73%) had Stage IIB disease, 5 (23%) Stage IIA, and 1 (4%) Stage IA. Thirteen (59%) completed all 6 cycles of therapy, of whom 9 required dose reduction. Of the remaining 9 pts, 4 completed &gt;68% of intended therapy. Grade 3 and 4 toxicity occurred in 13 pts (59%); neutropenia was most common (n=9;41%). Median follow-up was 37.5 mo. Median RFS was 16.7 mo, and OS was 35.5 mo. ERCC1 tumor expression data were available for 20 pts: 15 low (75%) and 5 high (25%). Low compared to high ERCC1 was not associated with improved RFS (12.4 vs 16.7 mo; p=0.68) or OS (Median not reached vs 21.6 mo; p=0.22). Conclusions: Adjuvant gemcitabine/cisplatin is tolerated by patients with resected pancreatic adenocarcinoma. RFS and OS for Gem/Cis appear promising compared to historic control. Tumor ERCC1 expression can be reliably evaluated, and low expression is present in the majority of patients. Further prospective trials evaluating Gem/Cis as an adjuvant regimen and ERCC-1 as a biomarker in resected pancreatic adenocarcinoma are warranted. Clinical trial information: NCT01188109.

Impact of excision repair cross-complementing gene 1 (ERCC1) on the outcomes of patients with advanced gastric cancer: correlative study in Japan Clinical Oncology Group Trial JCOG9912

BackgroundSince the best chemotherapy regimen for each patient with advanced gastric cancer is uncertain, we aimed to identify molecular prognostic or predictive biomarkers from biopsy specimens in JCOG9912, a randomized phase III trial for advanced gastric cancer. Patients and methodsEndoscopic biopsy specimens from primary lesions were collected in 445 of 704 randomized patients in JCOG9912. We measured the mRNA expression of excision repair cross-complementing group 1 (ERCC1), thymidylate synthase, dihydropyrimidine dehydrogenase, and five other genes, then, categorized them into low and high groups relative to the median, and examined whether gene expression was associated with efficacy end point. ResultsMultivariate analyses showed that high ERCC1 expression [HR 1.37; 95% confidence interval (CI) 1.08–1.75; P = 0.010], performance status ≥1 (HR 1.45; 95% CI 1.13–1.86; P = 0.004), and number of metastatic sites ≥2 (HR 1.66; 95% CI 1.28–1.86; P < 0.001) were associated with a poor prognosis, and recurrent disease (versus unresectable; HR 0.75; 95% CI 0.56–1.00; P = 0.049) was associated with a favorable prognosis. None of these molecular factors were a predictive marker for choosing irinotecan plus cisplatin or 5-fluorouracil rather than S-1. ConclusionThese correlative analyses suggest that ERCC1 is an independent prognostic factor for overall survival in the first-line treatment of gastric cancer. Clinical Trial NumberC000000062, www.umin.ac.jp.

Differential expression and prognostic value of ERCC1 and thymidylate synthase in resected gastric adenocarcinoma

Excision repair cross-complementing gene-1 (ERCC1) and thymidylate synthase (TS) are key regulatory enzymes whose expression patterns are associated with overall survival (OS) in several malignancies. Their expression patterns and prognostic value in resected gastric adenocarcinoma (GAC) are not known. In total, 109 patients who underwent resection for GAC between January 2000 and June 2011 had tissue available for analysis. The primary objective was to assess for the differential expression of ERCC1 and TS using immunohistochemistry. The secondary objective was to assess for the association between OS and the expression of ERCC1 and TS. The median follow-up was 21.2 months, and the median OS was 28.8 months. Resected GAC exhibited differential expression of ERCC1 (high expression, 23%; n = 25) and TS (high expression, 43%; n = 47). ERCC1 and TS expression were not associated with OS. In a subset analysis of patients who received chemotherapy (n = 73), high ERCC1 expression was associated with decreased OS (16.7 months vs 53.8 months; P = 0.03). After controlling for known adverse pathologic features, high ERCC1 expression persisted as a negative prognostic factor in multivariate Cox regression analysis (hazard ratio, 2.5; 95% confidence interval, 1.03-6.0; P = .04). Conversely, in patients who underwent resection only (n = 35), high ERCC1 expression demonstrated a trend toward improved OS (40.4 months vs 12.7 months; P = .10); a positive prognostic influence also was present on multivariate analysis (hazard ratio, 0.20; 95% confidence interval, 0.04-0.86; P = .03). Resected GAC exhibited differential expression of TS and ERCC1. Among all patients, ERCC1 and TS expression levels were not associated with OS. High ERCC1 tumor expression was associated with decreased OS in the patients who received chemotherapy but was associated with increased OS in those who underwent surgery alone. ERCC1 expression had prognostic value in resected gastric cancer, and further investigation is warranted.

Reply to an analysis of human equilibrative nucleoside transporter‐1, ribonucleoside reductase subunit M1, ribonucleoside reductase subunit M2, and excision repair cross‐complementing gene‐1 expression in patients with resected pancreas adenocarcinoma: Implications for adjuvant treatment

BACKGROUND Tumor overexpression of excision repair cross-complementing gene-1 (ERCC1) may be associated with decreased survival in patients with pancreas adenocarcinoma (PAC). Human equilibrative nucleoside transporter-1 (hENT1) and ribonucleoside reductase subunits M1 and M2 (RRM1 and RRM2) are integral to cellular transport and DNA synthesis and are implicated as poor prognostic factors in other malignancies. To the authors's knowledge, their role in PAC is not defined. METHODS A prospective database was used to randomly select 95 patients who underwent pancreaticoduodenectomy for PAC between January 2000 and October 2008. Immunohistochemical analysis was performed on tumor samples for hENT1, RRM1 and RRM2, and ERCC1. Main outcomes were recurrence-free survival (RFS) and overall survival (OS). RESULTS The median follow-up, RFS, and OS were 49 months, 10.6 months, and 15.5 months, respectively. The median tumor size was 3 cm. Approximately 26% of patients had positive microscopic margins, 61% had lymph node involvement, and 88% and 45% had perineural and lymphovascular invasion, respectively. High tumor expression of hENT1, RRM1, RRM2, and ERCC1 was present in 85%, 40%, 17%, and 16%, respectively, of patients. High hENT1 expression was associated with reduced RFS (9.5 months vs 44.5 months; P = .029), but not with OS. RRM1 expression was not associated with survival. High RRM2 expression was associated with reduced RFS (6.9 months vs 16.0 months; P < .0001) and decreased OS (9.1 months vs 18.4 months; P < .0001). High ERCC1 expression was associated with reduced RFS (6.1 months vs 15 months; P = .04) and decreased OS (8.9 months vs 18.1 months; P = .03). After accounting for known adverse tumor factors, high expression of RRM2 and ERCC1 persisted as negative prognostic factors for RFS and OS. A subset analysis of patients who received adjuvant therapy (n = 74) revealed the same negative effect of high RRM2 and ERCC1 expression on RFS and OS. CONCLUSIONS High tumor expression of RRM2 and ERCC1 are associated with reduced RFS and OS after resection of pancreas cancer. These biomarkers may help to personalize adjuvant therapy.

Differential expression and prognostic value of ERCC1 and thymidylate synthase in resected gastric adenocarcinoma.

38 Background: Excision repair cross complementing gene-1 (ERCC1) and thymidylate synthase (TS) are key regulatory enzymes whose expression patterns are variably associated with overall survival (OS) in several malignancies. For example, in lung cancer, high ERCC1 expression is inversely associated with OS depending on whether or not patients receive perioperative chemotherapy with surgery. The expression pattern and prognostic value of ERCC1 and TS in resected gastric adenocarcinoma (GAC) are not known. Methods: 109 patients who underwent resection of GAC between 1/00-6/11 had tissue available for analysis. Primary objective was to assess for differential expression of ERCC1 and TS using immunohistochemistry. Secondary objective was to assess for association of ERCC1 and TS expression with OS. Results: Median age was 64yrs. Median FU was 21.2mos and median OS was 28.8mos. Resected GAC exhibited differential expression of ERCC1 (23% high, n=25) and TS (43% high, n=47). ERCC1 and TS expression were not associated with OS. In a planned subset analysis, however, of patients who received chemotherapy (n=73), high ERCC1 expression was associated with decreased OS (16.7 vs. 53.8mos; p=0.03). After controlling for tumor size, margin, grade, T-stage, lymph node involvement, and presence of lymphovascular or perineural invasion, the negative prognostic value of high ERCC1 expression persisted on multivariate Cox regression analysis (HR 2.5; 95%CI: 1.03-6.0; p=0.04). By contrast, in patients who underwent resection only (n=35), high ERCC1 expression was associated with improved OS (40.4 vs. 12.7mos; p=0.10). This finding persisted on multivariate analysis (HR 0.20; 95%CI: 0.04-.86; p=0.03). Conclusions: Resected gastric adenocarcinoma exhibits differential expression of TS and ERCC1. TS expression is not associated with OS. However, similar to what is reported in lung cancer, high ERCC1 tumor expression is associated with decreased OS in patients receiving chemotherapy, but is associated with increased OS in those treated with surgery alone. ERCC1 expression has prognostic value in resected gastric cancer and further investigation is warranted.

P-0064 ERCC1 Overexpression Predicts Poor Prognosis in Patients with Gastric/GE Junction Adenocarcinoma Treated with Adjuvant Cisplatin-Based Chemotherapy

IntroductionAdjuvant chemotherapy is gaining an increasing role after curative resection for gastric cancer. Novel molecular markers could guide treatment decision-making, in order to better select candidates for adjuvant chemotherapy. The objective of our study was to analyze the status of excision repair cross-complementing gene 1 (ERCC1), thymidylate synthetase (TS) e p53, and correlate with outcome of patients who underwent adjuvant chemotherapy after curative resection for locally advanced gastric/GE junction adenocarcinoma. MethodsWe retrospectively evaluated patients with locally advanced gastric/GE junction adenocarcinoma (stage≥IB according to UICC classification), who underwent curative gastrectomy with D2 dissection, followed by adjuvant chemotherapy consisting of 4 to 6 courses of the ECF regimen (epirubicin 50 mg/m2 day 1, cisplatin 60 mg/m2 day 1, 5FU 200 mg/m2 protracted continuous infusion). Molecular analyses were performed on formalin-fixed paraffin-embedded tissues collected from surgical specimens. p53 mutations were analyzed by sequencing exons 4-10. Protein expression of ERCC1 and TS was assessed by immunohistochemistry (IHC), using specific monoclonal antibodies from Neomarkers. Real-time PCR (TaqMan assay) was performed to quantify mRNA ERCC1 expression. Statistical analyses were carried out using both Fisher'exact and Log Rank tests. ResultsSixty-eight patients were eligible for the study. There were 32 women (47%) and 36 men (53%). The median age was 69 (range: 30-74); UICC stage was III in 44 patients (65%). The median number of delivered chemotherapy cycles was 5.1 (range 4-6). With a median f-up was 40.5 months, disease-free and overall survival were 18.0 (95%CI: 13.4-22.76) and 56 months (95%CI: 44.87-67.13), respectively. We identified mutations in p53 in 21 out of 66 (32%) cases. ERCC1 expression was negative (score 0) in 14 out of 67 (21%) cases, whereas a positive score (score 1-3+) was observed in 53 (79%) cases. TS expression was negative (score 0) in 17 out of 67 (25%) cases, while a positive (score 1-3+) was found in 50 (75%) cases. High ERCC1 mRNA level was found in 19 out of 33 (57%) evaluable cases. Median overall survival was significantly longer in patients with ERCC1 negative tumors (p=0.04) by IHC, whilst TS, p53 and ERCC1 mRNA were not significantly associated with survival. ConclusionIn gastric/GE junction cancer patients after curative resection, ERCC1 by IHC might predict who is more likely to benefit from adjuvant platinum-based chemotherapy, according to the better overall survival observed in ERCC1 negative patients. In those exhibiting ERCC1 positive tumors, alternative chemotherapy regimens should be considered.

An analysis of human equilibrative nucleoside transporter‐1, ribonucleoside reductase subunit M1, ribonucleoside reductase subunit M2, and excision repair cross‐complementing gene‐1 expression in patients with resected pancreas adenocarcinoma

AbstractBACKGROUND:Tumor overexpression of excision repair cross‐complementing gene‐1 (ERCC1) may be associated with decreased survival in patients with pancreas adenocarcinoma (PAC). Human equilibrative nucleoside transporter‐1 (hENT1) and ribonucleoside reductase subunits M1 and M2 (RRM1 and RRM2) are integral to cellular transport and DNA synthesis and are implicated as poor prognostic factors in other malignancies. To the authors's knowledge, their role in PAC is not defined.METHODS:A prospective database was used to randomly select 95 patients who underwent pancreaticoduodenectomy for PAC between January 2000 and October 2008. Immunohistochemical analysis was performed on tumor samples for hENT1, RRM1 and RRM2, and ERCC1. Main outcomes were recurrence‐free survival (RFS) and overall survival (OS).RESULTS:The median follow‐up, RFS, and OS were 49 months, 10.6 months, and 15.5 months, respectively. The median tumor size was 3 cm. Approximately 26% of patients had positive microscopic margins, 61% had lymph node involvement, and 88% and 45% had perineural and lymphovascular invasion, respectively. High tumor expression of hENT1, RRM1, RRM2, and ERCC1 was present in 85%, 40%, 17%, and 16%, respectively, of patients. High hENT1 expression was associated with reduced RFS (9.5 months vs 44.5 months; P = .029), but not with OS. RRM1 expression was not associated with survival. High RRM2 expression was associated with reduced RFS (6.9 months vs 16.0 months; P &lt; .0001) and decreased OS (9.1 months vs 18.4 months; P &lt; .0001). High ERCC1 expression was associated with reduced RFS (6.1 months vs 15 months; P = .04) and decreased OS (8.9 months vs 18.1 months; P = .03). After accounting for known adverse tumor factors, high expression of RRM2 and ERCC1 persisted as negative prognostic factors for RFS and OS. A subset analysis of patients who received adjuvant therapy (n = 74) revealed the same negative effect of high RRM2 and ERCC1 expression on RFS and OS.CONCLUSIONS:High tumor expression of RRM2 and ERCC1 are associated with reduced RFS and OS after resection of pancreas cancer. These biomarkers may help to personalize adjuvant therapy. Cancer 2013. © 2012 American Cancer Society.

An analysis of ERCC1, hENT1, RRM1, and RRM2 expression in resected pancreas adenocarcinoma: Implications for adjuvant treatment.

206 Background: Tumor overexpression of excision repair cross complementing gene 1 (ERCC1) was recently shown to be associated with decreased survival in patients with pancreas adenocarcinoma (PAC). Ribonucleotide reductase 1 and 2 (RRM) and human equilibrative nucleotide transporter 1 (hENT1) are integral to DNA synthesis and cellular transport and are implicated as poor prognostic factors in other malignancies. Their role in PAC is not well defined. Methods: A prospective database (n=220) was used to randomly select 95 pts who underwent pancreaticoduodenectomy for PAC between 1/00-10/08. IHC analysis was performed on tumor samples for RRM1 and 2, hENT1, and ERCC1. Main outcomes were recurrence-free (RFS) and overall survival (OS). Results: Median age was 63 yrs; median FU, RFS, and OS was 49, 10.6 and 15.5 mo. Median tumor size was 3cm, 26% had a positive margin, 34% were poorly differentiated, 61% had positive lymph nodes (LN), 88% had perineural invasion (PNI), and 45% had lymphovascular invasion (LVI). High expression of RRM1, RRM2, hENT1, and ERCC1 was present in 40%, 17%, 85%, and 16% of patients, respectively. High RRM2 was associated with reduced RFS (6.9 vs 16.0 mo; p&lt;0.0001) and decreased OS (9.1 vs 18.4 mo; p&lt;0.0001). High ERCC1 was associated with reduced RFS (6.1 vs 15 mo; p=0.04) and decreased OS (8.9 vs 18.1 mo; p=0.03). RRM1 and hENT1 were not associated with survival. After accounting for known adverse factors, high RRM2 and ERCC1 persisted as negative prognostic factors for RFS and OS (Table). A subset analysis of those who received adjuvant therapy (n=74) revealed the same negative effect of high RRM2 and ERCC1 on RFS and OS. Conclusions: High RRM2 and ERCC1 tumor expression are associated with reduced RFS and OS after resection of pancreas cancer. These biomarkers may help personalize adjuvant therapy. [Table: see text]

Differential Expression of ERCC1 in Pancreas Adenocarcinoma: High Tumor Expression is Associated with Earlier Recurrence and Shortened Survival after Resection

Increased tumor expression of excision repair cross-complementing gene-1 (ERCC1) is associated with decreased survival in patients with various cancers. Its effect in pancreatic adenocarcinoma (PAC) is not defined. Ninety-five patients were selected from a prospective database of all patients (n=220) who underwent pancreaticoduodenectomy for PAC between January 2000 and October 2008. Tumor was isolated to perform immunohistochemistry for ERCC1 expression and was graded by a single pathologist. Main outcomes were recurrence-free survival (RFS) and overall survival (OS). Median age was 63years; 50 patients (53%) were male and 73 (77%) received adjuvant chemotherapy. Median follow-up was 25months. Median RFS and OS was 9 and 16months. Median tumor size was 3cm; 26% had a positive resection margin, 34% had poorly differentiated tumors, 61% had positive lymph nodes, 88% had perineural invasion, and 45% had lymphovascular invasion. Tumors exhibited differential ERCC1 expression in terms of intensity staining [none-weak: 61%; moderate-strong: 39%], percentage staining [0: 39%; 1-10: 29%; 11-50: 20%; 51-100: 12%], and overall expression [low: 84%; high: 16%]. High ERCC1 expression was associated with reduced RFS (6 vs. 10months; P=0.03) and decreased OS (9 vs. 18months; P=0.019). After accounting for adverse tumor factors, high ERCC1 expression persisted as a negative prognostic factor on multivariate Cox regression for both RFS and OS [hazards ratio (HR), 2.1; 95% confidence interval (CI), 1.1-3.9; P=0.02; HR, 3; 95% CI, 1.6-6; P=0.001, respectively]. A subset analysis of only those 73 patients who received adjuvant therapy revealed the same negative effect of high ERCC1 expression on RFS (4 vs. 15months; P=0.001) and OS (9 vs. 20months; P<0.001). Pancreas cancer exhibits differential expression of ERCC1. High ERCC1 expression is associated with both reduced RFS and OS after resection. ERCC1 expression levels may help to predict patient outcome with adjuvant chemotherapy.

Impacts of excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase, and epidermal growth factor receptor on the outcomes of patients with advanced gastric cancer

Using laser-captured microdissection and a real-time RT–PCR assay, we quantitatively evaluated mRNA levels of the following biomarkers in paraffin-embedded gastric cancer (GC) specimens obtained by surgical resection or biopsy: excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), epidermal growth factor receptor (EGFR), and five other biomarkers related to anticancer drug sensitivity. The study group comprised 140 patients who received first-line chemotherapy for advanced GC. All cancer specimens were obtained before chemotherapy. In patients who received first-line S-1 monotherapy (69 patients), low MTHFR expression correlated with a higher response rate (low: 44.9% vs high: 6.3%; P=0.006). In patients given first-line cisplatin-based regimens (combined with S-1 or irinotecan) (43 patients), low ERCC1 correlated with a higher response rate (low: 55.6% vs high: 18.8%; P=0.008). Multivariate survival analysis of all patients demonstrated that high ERCC1 (hazard ratio (HR): 2.38 (95% CI: 1.55–3.67)), high DPD (HR: 2.04 (1.37–3.02)), low EGFR (HR: 0.34 (0.20–0.56)), and an elevated serum alkaline phosphatase level (HR: 1.00 (1.001–1.002)) were significant predictors of poor survival. Our results suggest that these biomarkers are useful predictors of clinical outcomes in patients with advanced GC.

Clinical significance of dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and excision repair cross-complementing gene 1 (ERCC1) gene expression of tumor tissue in patients with advanced gastric cancer

4629 Background: Many methods for predicting the susceptibility of a gastric cancer(GC) to chemotherapy have been investigated. However, the clinical significance of biomarkers in GC cells remains unclear. There is a need for exploratory evaluations to understand the clinical implications of biomarkers. Methods: This study consisted of 151 patients (pts) who received chemotherapy for advanced GC. cDNA was derived from the laser-captured tumor cells of cancer specimens obtained by surgical resection or endoscopic biopsy and analyzed to determine mRNA expression relative to an internal reference gene (β-actin) using real-time RT-PCR method. Gene expression levels of thymidylate synthase (TS), DPD, orotate phosphoribosyl transferase, dihydrofolate reductase (DHFR), ERCC-1, EGFR and 22 other biomarkers related to anticancer drug sensitivity were measured. Results: DPD, EGFR, and ERCC1 gene expressions were significantly correlated with survival ( Table ). Multivariate analysis revealed that high DPD (p=0.0002, RR=2.67 [95% CI, 1.62–4.25]), low EGFR (p=0.0005, RR=0.29 [0.18–0.50]), and high ERCC1 (p&lt;0.0001, RR=2.27 [1.45–3.47]) gene expressions were independently related to poor survival. As for first-line chemotherapy, an analysis of 60 pts treated with S-1 showed that low DHFR gene expression significantly correlated with a longer time to progression (TTP) (p=0.0017). An analysis of 54 pts who received cisplatin containing regimens ( + irinotecan or + S-1) as first-line therapy showed that low ERCC1 gene expression was slightly related to a better response (p=0.053). Conclusions: These results indicate that expression of DPD, ERCC1, and EGFR gene expressions in cancer specimens have predictive value for the outcome of advanced GC pts treated with chemotherapy. Low DHFR gene expression could be a predictor of a long TTP in patients receiving S-1 therapy. [Table: see text] No significant financial relationships to disclose.

Relation between ERCC1 Expression in Sputum and Survival after Cisplatin-Based Chemotherapy in Patients with Non-Small Cell Lung Cancer

Background : Excision repair cross complementing gene 1 (ERCC1) not only has a protective role against carcinogens, but plays an important role in cisplatin-resistance via the repair of cisplatin-DNA adducts. This study investigated the association between the ERCC1 expression levels in sputum and survival after cisplatin-based chemotherapy in patients with inoperable non-small cell lung cancer (NSCLC). Methods : Using the sputum collected from 67 inoperable (stage IIIa-IV) NSCLC patients treated with either taxanes (33 cases) or gemcitabine (34 cases) plus cisplatin, the relative expression levels of ERCC1 and the expression of the tumor specific antigen, MAGE, were examined by the quantitative RT-PCR and RT-PCR, respectively. The response and survival were compared with the relative level of ERCC1 or MAGE expression and the treatment modality. Results : In the sputum, ERCC1 and MAGE was detected in 74.6% and 40.2% of patients, respectively. Using the median ERCC1 level, the patients were classified as having high or low ERCC1 expression. The median overall survival (MST) was significantly longer in patients with a high ERCC1 expression level than those with a low expression level (84 weeks vs. 44 weeks respectively, P=0.017). In the taxene-based treatment group, the MST was longer than the gemcitabine group (79 weeks vs. 47 weeks, respectively, P=0.03). The levels of ERCC1 were significantly higher in patients who were MAGE-positive (P=0.003). In the MAGE-negative patients, the MST was longer in the high ERCC1 group (103 weeks vs. 43 weeks, P=0.008), but not in the MAGE-positive patients (62 weeks vs. 44 weeks, P=0.348). Conclusion : ERCC1 expression in the sputum can be a prognostic factor for survival after chemotherapy in patients with inoperable NSCLC.