Patients with ERCC1-negative locally advanced esophageal cancers may benefit from preoperative chemoradiotherapy

PURPOSE: To assess the significance of excision repair cross-complementation group 1 (ERCC1) expression as a predictive marker, we analyzed the effects of preoperative chemoradiotherapy on survival relative to ERCC1 status in patients with locally advanced operable esophageal cancer. EXPERIMENTAL DESIGN: Paraffin-embedded pretreatment tumor specimens, collected by endoscopic biopsy from patients treated with surgery alone or with preoperative chemoradiotherapy followed by surgery, were immunohistochemically assayed for ERCC1 expression. RESULTS: Of the 175 patients, 152 biopsy specimens were available for immunohistochemical analysis. Based on a median ERCC1 expression score of 1, we divided the samples into ERCC1-positive (score >1; 71 patients, 47%) and ERCC1-negative (score 相似文献   

ERCC1 expression by immunohistochemistry and EGFR mutations in resected non-small cell lung cancer

Expression of excision repair cross-complementation group 1 (ERCC1) is important for resistance to platinum agents. Mutations of epidermal growth factor receptor (EGFR) are related to the responsiveness to tyrosine kinase inhibitors in non-small cell lung cancer (NSCLC). This study was performed to determine if ERCC1 expression and EGFR are related to the prognosis of resected NSCLC, and to determine if ERCC1 expression and EGFR mutations are related. We used immunohistochemistry (IHC) to evaluate ERCC1 expression in tumors from 130 patients with curatively resected NSCLC. The median H-score was used as a cut-off for ERCC1 IHC. EGFR mutations were analyzed in exons 18, 19 and 21. ERCC1 expression was detected in tumors from 80 patients (61.5%). ERCC1 was expressed more frequently in smokers and in squamous cell carcinomas. Patients with a positive ERCC1 expression survived longer than ERCC1-negative patients (median overall survival 7.6 years for ERCC1-positive vs. 4.0 years for ERCC1-negative, P=0.046). Subsequent multivariate analysis suggested that ERCC1 expression is an independent prognostic marker of longer survival (hazard ratio: 0.598, 95% confidence interval: 0.357-1.001). EGFR mutations were found in 25 patients (19.2%) but did not affect overall survival. Interestingly, EGFR mutations were more frequent in ERCC1-negative tumors (12.5% in ERCC1-positive vs. 30% in ERCC1-negative tumors, P=0.014). In conclusion, ERCC1 expression was identified as a positive prognostic marker in resected NSCLC. In addition, EGFR mutations were more frequently found in ERCC1-negative tumors.     

ERCC1 protein expression predicts the response of cisplatin-based neoadjuvant chemotherapy in non-small-cell lung cancer

The excision repair cross-complementation group 1 (ERCC1) and BRCA1 have been identified as predictors of clinical outcomes among patients with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. In this study, we immunohistochemically examined the ERCC1 and BRCA1 protein expression levels in 35 patients with metastatic mediastinal lymph nodes obtained prior to treatment as retrospective study. These patients had been enrolled in our studies on neoadjuvant chemotherapy with cisplatin and irinotecan (15 patients) or chemoradiotherapy with cisplatin and docetaxel plus concurrent thoracic radiation (20 patients). The relations between the ERCC1 or BRCA1 protein expression and the clinical outcomes of the patients were then examined. The rates of radiological response and pathological effectiveness were significantly higher among patients with ERCC1-negative tumors, compared with those with positive tumors in the neoadjuvant chemotherapy group (radiological response rates; 100% vs. 42.8%, P=0.013; pathological effectiveness; 100% vs. 47.1%, P=0.038), but no associations were observed in the neoadjuvant chemoradiotherapy group. Regarding survival, no significant differences in overall survival or disease-free survival were observed between patients with ERCC1-negative and positive tumors in both the neoadjuvant chemotherapy and chemoradiotherapy groups. In summary, we showed that a ERCC1-negative protein status was significantly related to tumor responsiveness to neoadjuvant chemotherapy with cisplatin and irinotecan, but such a status was not a clear prognostic predictor to cisplatin-based neoadjuvant therapy in NSCLC patients. Further study is needed to clarify the value of molecular predictors for customizing therapy for patients with NSCLC.     

Immunohistochemical expression of excision repair cross-complementing 1 (ERCC1) in non-small-cell lung cancer: implications for patient outcome

INTRODUCTION The identification of novel prognostic markers may help to better assess survival probability in different subgroups of patients with non-small-cell lung cancer (NSCLC) and to tailor treatment according to the molecular profile of the tumour. AIM We sought to examine whether the immunohistochemical expression of excision repair cross-complementing 1 (ERCC1), an essential component of the nucleotide excision repair pathway, may predict prognosis in NSCLC. MATERIAL AND METHOD Formalin-fixed paraffin-embedded tumour samples from 44 Turkish patients with NSCLC treated by adjuvant platinum-based chemotherapy were included in the study. Immunohistochemical expression levels of ERCC1 were correlated with clinical outcomes by Kaplan-Meier curves and multivariable Cox proportional hazards regression analysis. RESULTS A total of 29 patients had ERCC1-negative tumours while 15 had ERCC1-positive tumours. The mean progression- free survival (PFS) was significantly lower in patients with ERCC1-positive tumours (13±2 months) than in those with ERCC1-negative tumours (27±5 months, p<0.05). Similarly, the mean overall survival (OS) was significantly lower in patients with ERCC1-positive tumours (20±3 months) than in those with ERCC1-negative tumours (33±5 months, p<0.05). After allowance for potential confounders, Cox regression analysis demonstrated that ERCC1 expression was significantly associated with both PFS and OS (both p<0.05). CONCLUSION This study provides support for the prognostic value of ERCC1 immunohistochemical expression in patients with NSCLC treated by adjuvant platinum-based chemotherapy. If independently confirmed, these findings may improve prognostic stratification in this group of patients.     

Prognostic significance of ERCC1 expression in postoperative patients with gastric cancer

Aim： This study explored the correlation between the expression of excision repair cross-complementation group 1 （ERCC1） and the prognosis of gastric cancer patients. Methods： From January 2005 to December 2008, 605 patients who underwent radical surgery in The First Affiliated Hospital of Nanjing Medical University were enrolled. We conducted the follow-up every 6 months and its contents included a comprehensive medical history, tumor markers and abdominal ultrasound or CT and other imaging findings. Deadline was April 30, 2013 and follow-up time between 51 to 91 months. Survival time is calculated from the date of diagnosis to death or last follow-up date. Immunohistochemistry （IHC） was used to assess the expression of ERCCI in resected samples. The relationship between ERCCI expression and survival of patients was investigated. The comparison of count data were analyzed by Chi-square test. Median survival time （MST） and the 5-year survival rate were calculated by life table analysis. The Kaplan-Meier curves were used for survival analysis. Results： ERCC1 expression was positive in 412 patients （68.1%）. There is no significant difference between ERCCl-positive group and ERCCl-negative group in terms of the MST and 5-year survival rate （P=0.455）. The MST and 5-year survival rate have no significant difference （P=0.162） between group with chemotherapy and group with no chemotherapy in patients with ERCCl-positive expression. However, the MST and 5-year survival rate in patients with ERCCl-negative expression benefited more from with chemotherapy （P=0.019）. The ERCCl-positive patients survived longer than those ERCCl-negative patients （P=0.183） in subgroup with no adjuvant chemotherapy. In the subgroup analysis, ERCC 1 expression had no significant relationship with overall survival in patients with stage II or llI gastric cancer （P〉0.05）. Conclusions： ERCC1 might be a good prognostic factor for the patients of gastric cancer after radical resection. Patients with ERCC     

ERCC1 expression as a predictive marker of squamous cell carcinoma of the head and neck treated with cisplatin-based concurrent chemoradiation

The excision repair cross-complementation group 1 (ERCC1) enzyme plays a rate-limiting role in the nucleotide excision repair pathway and is associated with resistance to platinum-based chemotherapy. The purpose of this study was to evaluate the role of ERCC1 expression as a predictive marker of survival in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) treated with cisplatin-based concurrent chemoradiotherapy (CCRT). ERCC1 expression was assessed by immunohistochemical staining. The median age of the 45 patients analysed was 56 years (range 27-75 years), and 82% were men; 73% of all specimens showed high expression of ERCC1. The overall tumour response rate after CCRT was 89%. The median follow-up was 53.6 months (95% CI, 34.5-72.7 months). The 3-year progression-free survival (PFS) and overall survival (OS) rates were 58.7 and 61.3%, respectively. Univariate analyses showed that patients with low expression of ERCC1 had a significantly higher 3-year PFS (83.3 vs 49.4%, P=0.036) and OS (91.7 vs 45.5%, P=0.013) rates. Multivariate analysis showed that low expression of ERCC1 was an independent predictor for prolonged survival (HR, 0.120; 95% CI, 0.016-0.934, P=0.043). These results suggest that ERCC1 expression might be a useful predictive marker of locally advanced SCCHN in patients treated with cisplatin-based CCRT.     

非小细胞肺癌组织ERCC1和RRM1基因表达及其对预后影响探讨

目的比较非小细胞肺癌（non-small cell lung cancer,NSCLC）患者原发灶与转移淋巴结中切除修复交叉互补基因1（excision repair cross-complementation group1,ERCC1）和核糖核苷酸还原酶M1亚基（ribonucleotidereductase subunit M1,RRM1）表达情况,探讨ERCC1和RRM1表达状态与NSCLC患者治疗效果及预后的关系,为NSCLC患者的合理治疗提供依据。方法选取山东省肿瘤医院外科六病区2008-08-01-2012-08-31行手术切除且术后病理确诊为NSCLCⅡA-ⅢA期的患者106例,所有患者术前均未接受任何针对肿瘤的治疗措施,均釆用免疫组化技术测定组织中ERCC1和RRM1表达状况,术后均采用长春瑞滨联合顺铂（NP方案）进行辅助化疗,并进行临床随访。结果 NSCLC癌组织及转移淋巴结中RRM1阴性表达患者中位无疾病进展时间分别为23.1和24.7个月,显著优于RRM1阳性表达患者的16.4和19.1个月,两组比较差异有统计学意义,P值分别为0.007和0.026;而ERCC1阴性表达患者中位无疾病生存期为17.5个月,与ERCC1阳性表达患者的19.4个月比较,差异无统计学意义,P=0.59。原发灶和淋巴结转移灶中ERCC1和RRM1的表达水平差异无统计学意义,P〉0.05。不同性别、分期及病理类型的NSCLC患者ERCC1及RRM1表达水平差异均无统计学意义,P〉0.05。结论 NSCLC患者癌组织及转移淋巴结中,RRM1基因表达情况可作为NP方案术后辅助化疗预后的重要指标。     

Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy

The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72 months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (44.9% vs. 90.0%, respectively; P = 0.042). In a multivariate analysis, CD133 and ALDH1 negativity (P = 0.047) and cN2-3 single station metastasis (P = 0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy.     

ERCC1 and histopathology in advanced NSCLC patients randomized in a large multicenter phase III trial

BackgroundCustomized chemotherapy is likely to improve outcome in patients with advanced non-small-cell lung cancer (NSCLC). Excision repair cross-complementation group 1 (ERCC1) is a promising biomarker; however, current evidence is inadequate. Impact of ERCC1 status was evaluated among patients participating in a large randomized chemotherapy trial.Patients and methodsFour hundred and forty-three patients with advanced NSCLC were enrolled in a phase III trial and were randomly allocated to triplet chemotherapy or standard doublet regimen. Immunohistochemical evaluation for ERCC1 status was mainly carried out on bioptic material.ResultsTwo hundred and sixty-four (59.5%) patients had representative tissue samples for ERCC1 evaluation. Median overall survival (OS) in the ERCC1-negative and ERCC1-positive population was 11.8 and 9.8 months, respectively (P = 0.028). The median OS among patients with adenocarcinomas (n = 122) was 15.2 and 8.3 months, respectively (P = 0.007). Interaction analysis between ERCC1-negative status and adenocarcinomas yielded a hazard ratio of 0.64 for death (P = 0.002).ConclusionsClinically applicable evaluation of ERCC1 status predicted cisplatin sensitivity in the largest randomized patient population with advanced NSCLC reported to date. The predictive value can be ascribed to the adenocarcinomas emphasizing the relevance of ERCC1 expression in this subgroup.     

核苷酸切除修复交叉互补基因1 mRNA表达与非小细胞肺癌铂类化疗患者预后的相关性

目的 探讨核苷酸切除修复交叉互补基因1(ERCC1)mRNA表达与非小细胞肺癌(NSCLC)铂类化疗患者临床病理特征的关系及其预后意义.方法 采用实时荧光定量逆转录聚合酶链反应(RT-PCR)方法,检测NSCLC石蜡包埋组织中ERCC1 mRNA的表达水平,并比较其表达水平与NSCLC铂类化疗患者临床病理特征和生存时间之间的关系.结果 61例NSCLC患者中,ERCC1 mRNA的中位表达量为0.48.ERCC1 mRNA表达与NSCLC患者临床病理特征无关.ERCC1mRNA低表达(<0.35)患者经铂类药物化疗后的无进展生存时间为14.3个月,而高表达者为8.0个月,差异有统计学意义(P=0.028).ERCC1 mRNA低表达(<0.28)患者的总生存时间为28.4个月,而高表达者为12.9个月,差异有统计学意义(P=0.0064).Cox多因素回归分析显示,ERCC1 mRNA表达水平是影响NSCLC患者预后的独立因素.结论 ERCC1 mRNA的表达水平可以作为以铂类为基础药物化疗的NSCLC患者预后的独立预测因素,ERCC1 mRNA低表达的NSCLC患者经铂类化疗后,总生存时间明显延长,为制定NSCLC个体化的化疗方案提供了重要信息.     

Is trimodality approach better then bimodality in stage IIIA, N2 positive non-small cell lung cancer?

BACKGROUND: Neoadjuvant treatment followed by surgery is currently being investigated for locally advanced non-small cell lung cancer (NSCLC). This study reports efficacy, toxicity and feasibility of neoadjuvant chemotherapy with concurrent radiotherapy (CCRT) in stage IIIA, N2 positive NSCLC. METHODS: From March 2001 to February 2004, 52 patients with histologically confirmed stage IIIA, N2 positive NSCLC were registered. Patients received preoperative CCRT that consisted of weekly paclitaxel plus platinum chemotherapy and concurrent radiotherapy followed by surgery. RESULTS: Overall response rate was 76.9% (95% CI, 64-88%). The major grade 3-4 toxicities were radiation esophagitis (15.4%) and neutropenia (11.5%), and treatment-related mortality rate was 1.9%. Forty-two of 52 patients (80.8%) subsequently underwent surgical resection and 35 of 52 patients (67.3%) underwent complete resection. Among them, pathological complete response was obtained in 4.8%. Pathological downstaging rate to N0-1 and stage 0-II at surgery were 69.0% and 66.7%, respectively. The perioperative major morbidity rate was 23.8% and perioperative mortality was 2.4%. At a median follow-up of 33.9 months (range: 16.4-49.9), the median progression-free survival and overall survival were 16.5 months (95% CI, 6.2-26.8) and 25.6 months (95% CI, 14.6-36.6), respectively. Multivariate analyses identified that patients achieved mediastinal nodal clearance (downstage to pathological N0 or N1) after CCRT (p=0.02) and age at diagnosis<60 years (p=0.01) showed significantly improved survival. CONCLUSION: Neoadjuvant CCRT showed a high overall response rate with tolerable toxicity profile. Downstaging after CCRT may increase the rate of complete tumor resection and result in survival benefit in stage IIIA, N2 positive NSCLC patients.     

Wnt1 overexpression associated with tumor proliferation and a poor prognosis in non-small cell lung cancer patients

The Wnt family genes encode multifunctional signaling glycoproteins that are involved in the regulation of a wide variety of normal and pathological processes including tumorigenesis. In order to clarify the clinical significance of the intratumoral Wnt1 expression in non-small cell lung cancer (NSCLC), we performed an immunohistochemical study on the Wnt1 expression in NSCLCs in relation to the tumor proliferation. The intratumoral Wnt1 protein expression appeared in a cytoplasmic staining pattern. Of the 151 NSCLCs studied, 61 carcinomas (40.4%) were Wnt1-positive. Regarding the tumor biology of the intratumoral Wnt1 expression, the Ki-67 proliferation index was significantly higher in Wnt1-positive than in Wnt1-negative tumors (P=0.0062). Furthermore, regarding the expression of c-Myc, one of the proliferation-regulating Wnt targets, the percentage of c-Myc-positive tumor cells was significantly higher in Wnt1-positive than in Wnt1-negative tumors (P=0.0019). The Ki-67 proliferation index was significantly higher in c-Myc-positive than in c-Myc-negative tumors (P=0.0239). The overall survival was significantly lower in patients with Wnt1-positive NSCLCs than in patients with Wnt1-negative NSCLCs (P=0.0003). A Cox regression analysis demonstrated that the Wnt1 status was a significant prognostic factor for NSCLC patients (hazard ratio 1.983; P=0.0061). Our results revealed that the Wnt1 overexpression affects the tumor proliferation in NSCLCs, partly via the upregulation of c-Myc.     

Different relation between ERCC1 overexpression and treatment outcomes of two platinum agents in advanced biliary tract adenocarcinoma patients

Purpose

The aim of this study is to evaluate the effect of excision repair cross-complementation group 1 (ERCC1) expression on treatment outcomes in advanced biliary tract adenocarcinoma (ABTA) patients treated with platinum-based chemotherapy.

Methods

One hundred and six patients with histologically confirmed adenocarcinoma of biliary tract were enrolled at 5 institutions in South Korea between January 2002 and September 2008. Of 106 patients, 93 were assessed by immunohistochemistry from tissue specimens. Sixty-five patients were treated with cisplatin-based regimens and the other 28 treated with oxaliplatin-based ones.

Results

For total study population, no significant differences were noted in progression-free survival (PFS) and overall survival (OS) between ERCC1-negative and ERCC1-positive patients, respectively (4.2 vs. 2.9?months, p?=?0.116; 7.0 vs. 7.8?months, p?=?0.143). In patients treated with cisplatin-based regimens, median PFS and OS were significantly longer in ERCC1-negative group than in ERCC1-positive group, respectively (4.6 vs. 1.9?months, p?=?0.014; 9.1 vs. 7.9?months, p?=?0.017). Disease control rate (DCR) was better in patients with ERCC1 negative than in patients with ERCC1 positive (p?=?0.048). On the other hand, in patients treated with oxaliplatin-containing regimens, median PFS and OS tended to be longer in ERCC1-positive group, but these did not reach statistical significances. Response rate was better in patients with ERCC1 positive (p?=?0.005).

Conclusions

ERCC1 shows a significant prognostic value in ABTA patients treated with cisplatin. A survival benefit was observed in ERCC1-negative patients from cisplatin-containing chemotherapy but not from oxaliplatin-containing ones. The action mechanism of ERCC1 on cisplatin may be different from that on oxaliplatin.     

Randomized Phase II Trial Comparing Chemoradiotherapy with Chemotherapy for Completely Resected Unsuspected N2-Positive Non–Small Cell Lung Cancer

IntroductionWe investigated whether concurrent chemoradiotherapy (CCRT) would increase survival in patients with completely resected unsuspected N2-positive NSCLC versus in patients who received adjuvant chemotherapy alone.MethodsEligible patients were randomly assigned (1:1) to either the CCRT arm or the chemotherapy arm. In the CCRT arm, patients received concurrent thoracic radiotherapy (50 Gy in 25 fractions) with five cycles of weekly paclitaxel (50 mg/m²) and cisplatin (25 mg/m²), followed by two additional cycles of paclitaxel (175 mg/m²) plus cisplatin (80 mg/m²) at 3-week intervals. In the chemotherapy arm, patients received four cycles of adjuvant paclitaxel (175 mg/m²) and carboplatin (area under the curve = 5.5) every 3 weeks. The primary end point was disease-free survival.ResultsWe enrolled and analyzed 101 patients (51 received CCRT and 50 received chemotherapy). In all, 74 and 27 patients were preoperatively staged as N0 and N1 diseases, respectively. The baseline characteristics were well balanced between the two arms. The median disease-free survival of the CCRT arm was 24.7 months, which was not significantly different from that of the chemotherapy arm (21.9 months) (hazard ratio = 0.94, 95% confident interval: 0.58–1.52, p = 0.40). There was no difference in overall survival (74.3 months in CCRT arm and 83.5 months in the chemotherapy arm) (hazard ratio = 1.33, 95% confident interval: 0.71–2.49).ConclusionsThere was no survival benefit from adjuvant CCRT compared with from platinum-based chemotherapy alone for completely resected unsuspected N2-positive NSCLC. However, the role of sequential radiotherapy administered after adjuvant chemotherapy is being evaluated, and further study is needed to evaluate the optimal radiotherapy approach for completely resected N2-positive NSCLC.     

ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine.

BACKGROUND: Pivotal studies indicate a role of excision repair cross-complementation 1 (ERCC1) gene and ribonucleotide reductase M1 (RRM1) gene in conferring a differential sensitivity to cytotoxic chemotherapy and epidermal growth factor receptor (EGFR) gene has been recently extensively investigated in non-small-cell lung cancer (NSCLC). DESIGN: Formalin-fixed, paraffin-embedded bronchoscopic/fine needle aspiration biopsies obtained from 70 patients with advanced NSCLC were retrospectively collected to investigate the expression level of ERCC1, RRM1 and EGFR by real-time PCR. Sufficient amounts of messenger RNA (mRNA) were successfully extracted from 61 (87%) specimens, reverse transcribed and amplified with intron-spanning primers. Forty-one patients had stage IV disease and 43 received cisplatin/gemcitabine chemotherapy. RESULTS: A strong correlation between ERCC1 and RRM1 mRNA levels (r(s) = 0.624, P < 0.0001) was found. Median survival time in patients with low ERCC1 was significantly longer (17.3 versus 10.9, P = 0.0032 log-rank test) as well as in patients with low RRM1 (13.9 versus 10.9, P = 0.0390 log-rank test). Concomitant low expression levels of ERCC1 and RRM1 (n = 33) were predictive of a better outcome (14.9 versus 10.0, P = 0.0345 log-rank test). Among cisplatin-treated patients, a low ERCC1 level was highly predictive of a longer survival (23.0 versus 12.4, P = 0.0001 log-rank test). No correlation between gene expression levels and histology was reported. No significant correlation between EGFR expression level and survival was found. At multivariate analysis, performance status, response to chemotherapy, presence of weight loss and ERCC1 were independent prognostic factors for survival. CONCLUSIONS: This retrospective study further validates ERCC1 and RRM1 genes as reliable candidates for customized chemotherapy and shows a higher impact on the survival of NSCLC patients treated with cisplatin/gemcitabine for ERCC1. Prospective pharmacogenomic studies represent a research priority in early and advanced NSCLC.     

Chemokine receptor CXCR4 and early-stage non-small cell lung cancer: pattern of expression and correlation with outcome.

BACKGROUND: The expression of CXCR4 has been implicated in metastatic dissemination in different models of breast cancer and melanoma. In the present study, we evaluated CXCR4 expression in non-small-cell lung cancer (NSCLC) and the relationship between CXCR4 expression and the prognosis of stage I disease. PATIENTS AND METHODS: Using immunohistochemical analysis, we retrospectively analyzed CXCR4 expression in specimens from 61 patients with completely resected pathologically confirmed stage I NSCLC for whom clinical follow-up data were available. RESULTS: In the present study, we have shown that: CXCR4 is expressed by tumor cells in stage I NSCLC; CXCR4 is located in the nucleus and/or in the cytoplasm of tumor cells; strong nuclear staining was observed in 17 cases (29.8%); patients whose tumors had CXCR4-positive nuclear staining had a significantly longer duration of survival than patients whose tumors had no nuclear expression (P = 0.039, log-rank test). Interestingly, the 5-year metastasis rates were 23.5% and 34.1% in patients with CXCR4-positive and CXCR4-negative nuclear expression, respectively (P = 0.2). CONCLUSION: Strong CXCR4-positive nuclear staining was associated with a significantly better outcome in early-stage NSCLC. The mechanisms underlying this clinically and biologically important finding need to be further explored.     

Eg5 expression is closely correlated with the response of advanced non-small cell lung cancer to antimitotic agents combined with platinum chemotherapy

BACKGROUND: Eg5 is a microtubule motor protein that functions in bipolar spindle assembly. We investigated the relationship between Eg5 expression and the response to chemotherapy of patients with advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eg5 expression was investigated immunohistochemically in 122 formalin-fixed tumor samples from untreated stage IIIB or IV NSCLC patients. We also investigated cyclin B1 expression, which is involved in the G2/M transition. All patients received antimitotic agents combined with platinum chemotherapy. The response to chemotherapy was compared in relation to Eg5 and cyclin B1 expression and in relation to clinicopathological factors. RESULTS: The response rate to chemotherapy of patients with Eg5-positive tumors was 37%, as opposed to 10% for patients with Eg5-negative tumors, and Eg5 expression was significantly associated with the response to chemotherapy (P=0.002). The response rate of patients with cyclin B1-positive tumors (53%) was higher than that of patients with cyclin B1-negative tumors (23%) (P=0.009), and Eg5 expression was significantly correlated with cyclin B1 expression (P=0.005). A multivariate analysis confirmed Eg5 status to be an independent variable related to response to chemotherapy (P=0.008). CONCLUSIONS: Eg5 expression can predict a response to antimitotic agents combined with platinum chemotherapy among patients with advanced NSCLC.     

测定晚期非小细胞肺癌患者ERCC1表达水平选用个体化疗方案的临床研究

目的:探讨DNA切除修复基因ERCC1在晚期非小细胞肺癌(non-small cell lung callcer,NSCLC)中的表达与非铂类及铂类化疗方案敏感性的关系.方法:青海大学附属肿瘤医院2006年2月1日～2008年6月30日经病理组织学诊断的Ⅲb-Ⅳ期NSCLC患者130例,采用免疫组化法检测130例患者肿瘤组织中错配切除修复蛋白(exci-sion repair coross complementl(ERCC1)表达水平,并将其分组治疗:A组:ERCC1阴性患者,选用第三代新药含铂类方案;B组:ERCC1阳性患者,选用第三代新药非铂类方案;C组:ERCC1阳性患者选用第三代新药含铂类方案.结果:在130例病理组织中ERCC1阳性率为47.8%(62/130),ERCC1鳞癌中为35.7%(25/70),在腺癌中表达为62.4%(25/40),在腺癌和鳞癌中的表达差异有统计学意义,X~2=7.366,P=0.007.A组、B组和C组化疗有效率分别为58.8%(40/68)、51.6%(16/31)及32.3%(10/31),A、C组间差异有统计学意义,X~2=6.011,P=0.014.B、C组比较化疗疗效提高,但差异无统计学意义,X~2=2.384,P=1.123;A、B组差异无统计学意义,X~2=0.451,P=0.502.A组中住生存期为12.0个月,B组为11.0个月,C组为7.8个月,A、B组间差异无统计学意义,X~2=3.809,P>0.051;A、C组间差异有统计学意义,X~2=46.368,P<0.001;C、B组间差异有统计学意义,X~2=21.251,P<0.001.结论:ERCC1阴性表达患者选用第三代新药加铂类两药方案有较好化疗疗效及可延长生存,ERCC1阳性表达患者选用第三代新药非铂类两药方案可提,高化疗疗效及生存;ERCC1表达可以作为晚期NSCLC含铂方案化疗敏感性预测的指标,根据分子预测指标对制定个性化治疗计划的可行性.     

Ⅲa（T1N2M0）期非小细胞肺癌临床和预后影响因素分析

目的:回顾性分析Ⅲa（T1N2M0）期非小细胞肺癌（NSCLC）的临床及预后影响因素,并检测核苷酸切除修复交叉互补组1（ERCC1）和细胞角蛋白19（CK19）等与肿瘤发生、侵袭及转移相关的指标在本组肺癌组织中的表达情况,以此探讨此类型NSCLC的临床及生物学特征。方法:选取2000年1月1日至2003年12月31日在天津医科大学肿瘤医院肺部肿瘤科入院行手术治疗的49例Ⅲa（T1N2M0）期患者,对其病历资料进行随访。收集上述患者的肿瘤组织石蜡切片,采用免疫组织化学方法(SP法),检测ERCC1、CK19等指标在上述类型NSCLC中的表达状况,并进一步分析其与临床病理分期及预后的关系。结果:本组共49例NSCLC患者,总体1年、3年、5年生存率分别为79.59%、30.61%、12.24%。ERCC1和CK19的阳性率分别为38.78%和42.86%。单因素分析:肿瘤直径、纵隔淋巴结是否单站转移和是否行免疫治疗对本组患者的预后影响有统计学意义（P<0.05）;Cox回归多因素分析提示肿瘤直径（P=0.048）、纵隔淋巴结是否单站转移（P=0.045）、ERCC1和CK19的表达情况是影响患者总生存率的独立因素。结论:Ⅲa（T1N2M0）期NSCLC预后优于其他临床N2期肺癌。ERCC1、CK19的表达、肿瘤直径、纵隔淋巴结是否单站转移是影响本组患者预后的独立因素。