Her-2/neu expression in locally advanced breast carcinomas: pre- and post-neoadjuvant chemotherapy

Clinical studies have shown a correlation of HER-2/neu amplification/over-expression and favorable response to neoadjuvant chemotherapy and anti-HER-2/neu antibody treatment. However, contradictory findings also have been reported. Some tumors may develop resistance to neoadjuvant chemotherapy after an initial period of sensitivity. Our study attempts to evaluate the effects of neoadjuvant chemotherapy on HER-2/neu status in locally advanced breast cancer. Thirty-nine patients with locally advanced breast cancers established by core needle biopsy received neoadjuvant chemotherapy and were compared with 60 patients with breast cancers who did not receive neoadjuvant chemotherapy. IHC for HER-2/neu was performed on paraffin sections of the core biopsy before treatment and the excised specimen following chemotherapy and scored as Negative (0-1+), 2+ and 3+. The results of the study and the controls were compared and analyzed using Fisher's exact test. HER-2/neu IHC scores decreased in 28.5% (15/39) of patients receiving neo-adjuvant chemotherapy compared to 11.7% (7/60) of patients in the control (p < 0.013). HER-2/neu IHC status changed from strongly positive to negative (3+ to 0) in five of 39 (12.5%) in the study group and in 2 of 60 (3.3%) in control group (p = 0.104). For patients receiving neoadjuvant chemotherapy in whom the tumor becomes refractory to chemotherapy or recurs, repeat testing for HER-2/neu status may be necessary. Elimination of HER-2/neu positive tumor cells may account for the changes in the IHC scores and the development of resistance to neoadjuvant chemotherapy.     

Combined GADD45A and thymidine phosphorylase expression levels predict response and survival of neoadjuvant-treated gastric cancer patients.

PURPOSE: We evaluated the expression of seven therapy-related genes to predict the clinical outcome of advanced gastric cancer patients treated with a neoadjuvant chemotherapeutic protocol. EXPERIMENTAL DESIGN: Pretherapeutic, formalin-fixed, and paraffin-embedded biopsies of 61 patients, who received a 5-fluorouracil (5-FU)- and cisplatin-based chemotherapy were studied. The expressions of the 5-FU-related genes TS, DPD, and TP and of the cisplatin-related genes ERCC1, ERCC4, KU80, and GADD45A were analyzed by quantitative real-time PCR. The expression levels of single genes and of various combinations were tested for an association with response and overall survival. RESULTS: High DPD levels were more frequently found in nonresponding patients and were associated with worse survival. GADD45A and TP levels showed weak associations with response, but GADD45A expression correlated with survival. There was no association with response for TS expression, but tumors with a high TS level were associated with worse survival. The combination of GADD45A and TP revealed the strongest predictive effect. High expression values of TP and/or GADD45A were exclusively found in nonresponding patients (P = 0.002) and were associated with a significantly poorer survival (P = 0.04). CONCLUSIONS: Combined gene expression levels of TP and GADD45A represent a new variable to predict the clinical outcome after neoadjuvant chemotherapy in gastric cancer. The association of DPD expression with response and survival underlines a predominant role of DPD to predict 5-FU sensitivity. The association of TS expression levels with survival but not with response suggests an importance of this gene for tumor progression.     

HER-2/neu expression as a predictive factor for response to anthracycline-based chemotherapy in a Mexican Population of locally advanced breast cancer patients

Breast cancer is the second most frequent tumor in Mexico—30–50% are diagnosed in locally advanced stages requiring neoadjuvant chemotherapy. The overexpression of HER-2/neu has been identified as a chemotherapy response predictor. The objective of our study was to identify response predictive factors to anthracycline-based neoadjuvant chemotherapy in locally advanced breast cancer. Data were collected from clinical records of patients with neoadjuvant anthracycline-based chemotherapy, for clinical stage III breast cancer from 1992 to 1997. Paraffin blocks were reviewed to determine histologic grade, HER-2/neu expression, and ploidy. Patients were divided in two groups: A, 56 cases responding to chemotherapy and, B, 20 nonresponders. Mean age was 50.1 and 45.4 for groups A and B, respectively (OR 7.02, p=0.004), and those premenopausal were 43% and 70%, respectively (OR 3.1, p=0.04). Mean tumor size was 5 cm in responders and 8 cm for nonresponders (OR 4, p=0.02). Clinical stage III-B 16% and 70% for groups A and B (OR 12.2, p=0.000); tumors were aneuploid in 39% of responders and 18.7% for nonresponders. HER-2/neu was overexpressed in 64.2% and 50% for groups A and B (OR 3.6, p=0.06). On multivariate analysis significance was conserved only for age, clinical stage, and size. HER-2/neu lost significance. Age and size were importantly related to tumor response, a higher percentage of HER-2/neu overexpression was observed in responders, without significance due to small sample size. It would be important to study a larger number of patients to obtain more conclusive results.     

Kinetics of serum HER-2/neu changes in patients with HER-2-positive primary breast cancer after initiation of primary chemotherapy

BACKGROUND: The purpose of the study was to determine the utility of quantitation of the extracellular domain (ECD) of the HER-2/neu receptor in the serum for predicting response to treatment in patients with primary breast cancer receiving neoadjuvant therapy. METHODS: HER-2/neu ECD was measured in sera obtained from 39 patients with HER-2-amplified stage II-III primary breast cancer undergoing neoadjuvant chemotherapy. Patients were randomly assigned to either 4 cycles of paclitaxel followed by 4 cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC) (n = 10) or to the same chemotherapy with simultaneous weekly trastuzumab for 24 weeks (n = 29). Changes in HER-2 ECD were monitored with the Bayer HER-2/neu assay over 6 months and correlated with pathological response to treatment. RESULTS: Before initiation of chemotherapy, 28.2% of patients had elevated concentration of the HER-2 ECD (>15 ng/mL). The median baseline serum HER-2 ECD concentration was 13.6 ng/mL (mean +/- SD, 20.3 +/- 35.5 ng/mL). A decrease in the median HER-2 ECD levels from baseline to Week 3 and from baseline to Week 6 of chemotherapy was seen regardless of treatment regimen. No significant difference in baseline HER-2 ECD levels was observed between the groups who achieved pathological complete response (pCR) and the group with residual disease (P = .41). However, a 9% drop from Week 3 to Week 6 after initial chemotherapy was predictive of pCR (P = .04). CONCLUSION: A decrease in serum HER-2 ECD levels early during treatment was associated with pathological response in patients receiving primary chemotherapy, particularly trastuzumab-based regimens. Serum HER-2 ECD levels may serve to monitor neoadjuvant therapy in HER-2-positive primary breast cancer.     

Prognostic and Predictive Impact of the HER-2/neu Extracellular Domain (ECD) in the Serum of Patients Treated with Chemotherapy for Metastatic Breast Cancer

BACKGROUND: The extracellular domain of the HER-2/neu -receptor (ECD) is shed from the receptor protein and can be detected in serum. However, the clinical implication of HER-2/neu ECD measurement must be further evaluated. METHODS: In patients with metastatic breast cancer participating in a trial on first-line chemotherapy, the association of serum HER-2/neu ECD with progression-free interval, survival, and response was studied. Blood samples of patients receiving epirubicin and either cyclophosphamide (EC) or paclitaxel (ET) were collected before (n = 103) and in addition, after three courses of therapy (n = 46). RESULTS: HER-2/neu ECD levels correlate with HER-2/neu overexpression of corresponding primary tumors determined by immunohistochemistry (antibody CB11, p = 0.018) with an optimized cut-off at 15 ng/mL. Elevated serum levels of HER-2/neu ECD before chemotherapy were correlated with shorter overall survival (p = 0.0097), but not with reduced progression-free survival and response to chemotherapy. In subgroup analyses, patients with elevated pretherapeutic HER-2/neu ECD levels treated with EC showed shorter overall survival (p = 0.0092); no difference was seen in the ET group. With regard to progression-free survival, patients with elevated HER-2/neu ECD levels tended to benefit from ET (p = 0.0341), in patients with low levels no difference was observed between EC and ET. A decrease of HER-2/neu ECD levels after three courses of therapy was associated with response to therapy (p = 0.006). CONCLUSION: In our group of metastatic breast cancer patients, elevated HER-2/neu ECD levels are associated with decreased overall survival. With regard to progression-free survival, particularly patients with high HER-2/neu ECD levels seem to benefit from taxane-containing chemotherapy.     

ERCC1 mRNA levels and survival of advanced gastric cancer patients treated with a modified FOLFOX regimen

Molecular markers involved in DNA repair can help to predict survival in gastric cancer patients treated with 5-FU plus platinum chemotherapy. Excision repair cross-complementing 1 (ERCC1) and thymidylate synthase (TS) mRNA expression levels were assessed in advanced gastric cancer tumour samples using real-time quantitative PCR in 76 patients treated with a modified FOLFOX (biweekly oxaliplatin plus 5-FU and folinic acid) regimen. Median survival time in patients with low ERCC1 levels was significantly longer than in those with high levels (15.8 vs 6.2 months; P<0.0001). Patients with high TS levels had longer survival than those with low levels (12.2 vs 10.1 months; P=0.01). Forty-eight patients with low ERCC1 and high TS levels had a median survival of 16.1 months (P<0.0001). The hazard ratio for patients with high ERCC1 expression was 9.4 (P<0.0001). In patients with high mRNA levels of ERCC1, alternative chemotherapy regimens should be considered.     

Serum EGFR and serum HER-2/neu are useful predictive and prognostic markers in metastatic breast cancer patients treated with metronomic chemotherapy

BACKGROUND: Metronomic chemotherapy has been demonstrated to be of value in patients with advanced breast cancer. No reliable markers of response are available. In breast tumor, HER-2/neu is a prognostic factor, whereas no definite data exist for EGFR. The aim of the study was to evaluate the prognostic and predictive role of serum HER-2/neu and serum EGFR in breast cancer patients treated with low-dose chemotherapy. METHODS: Serum levels of HER-2/neu (n = 135) and of EGFR (n = 113) were prospectively determined before the start of chemotherapy, after 2 months of treatment, and when progressive disease was diagnosed. RESULTS: Elevated (>15 ng/mL) serum HER-2/neu before the start of chemotherapy was not associated with response rate, whereas elevated serum HER-2/neu at 2 months was significantly associated with reduced long-term clinical benefit (24 weeks) (P < .001), as well as changes in HER-2/neu levels between baseline and 2 months (P < .0001). Multivariate analysis identified a >or=20% increase of serum HER-2/neu as an independent factor for progression-free survival (PFS). Kinetics of serum HER-2/neu were significantly associated with PFS (P < .0001) and overall survival (OS) (P = .015). Low baseline serum levels of EGFR (<45 ng/mL) were predictive of reduced response rate both at 2 months (P = .031) and after 24 weeks (P = .022). Moreover, they were significantly associated with reduced PFS (P = .016) and OS (P = .015). CONCLUSIONS: Serum HER-2/neu and EGFR may represent useful markers for early prediction of probability of response, PFS, and OS in patients with advanced breast cancer treated with metronomic chemotherapy.     

Study of pretreatment serum levels of HER-2/neu oncoprotein as a prognostic and predictive factor in patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: HER-2/neu tissue overexpression is found in nearly 15% of patients with nonsmall cell lung carcinoma and is reported to affect prognosis adversely in surgical series. However, the prognostic role of serum HER-2/neu oncoprotein, particularly in patients with advanced lung carcinoma, remains unknown. This study was designed to assess the potential value of measuring serum levels of HER-2/neu oncoprotein in predicting response to treatment and survival in patients with locally advanced and metastatic nonsmall cell lung carcinoma. METHODS: Baseline serum HER-2/neu levels (fm/mL) were studied using an enzyme-linked immunosorbent assay method in 84 patients with newly diagnosed, advanced nonsmall cell lung carcinoma who underwent chemotherapy. RESULTS: The patients enrolled in the study included 76 males and 8 females, with a median age of 62 years (range, 36-73 years) and a median performance status of 1. Fifty patients (59.5%) had nonsquamous histology, and 34 patients (40.5%) had squamous cell carcinoma. Thirty-four patients (40.5%) had Stage III disease, and 50 patients (59.5%) had Stage IV disease. The mean baseline value of HER-2/neu in the whole series was 56.1 fm/mL (range, 13.0-103.8 fm/mL). HER2 immunohistochemistry on paraffin embedded tissue was performed in 18 patients. HER-2/neu tissue overexpression was found in only one patient, who also showed high serum levels (102 fm/mL). No correlation was observed between protein serum quantitation and gender, age, histology, stage, performance status, leukocyte count, or smoking. Nonresponding and responding patients exhibited similar oncoprotein levels (median, 57.6 fm/mL vs. 51.9 fm/mL, respectively). The overall survival rate was 42.5% at 1 year and 12% at 2 years, with a median survival duration of 10 months. At univariate analysis, high HER-2/neu serum levels were associated with an unfavorable survival outcome. Using a cut-off point for HER-2/neu of 73.0 fm/mL (corresponding to the 80th percentile of protein concentration), the survival of patients who had higher serum levels of HER-2/neu was significantly worse compared with patients who had lower serum levels (median, 7.1 months vs. 10.9 months; P = 0.004). Multivariate analysis confirmed the independent predictive value of serum HER-2/neu concentration as a negative prognostic factor (P = 0.02). CONCLUSIONS: High pretreatment levels of HER-2/neu oncoprotein are associated with an adverse prognostic impact on survival in patients with locally advanced or metastatic nonsmall cell lung carcinoma.     

生存素乳腺癌耐药蛋白和人表皮生长因子受体2基因的表达与乳腺癌新辅助化疗疗效的关系

目的 探讨生存素(Survivin)、乳腺癌耐药蛋白(BCRP)以及人表皮生长因子受体2(HER-2)基因表达对乳腺癌TE方案新辅助化疗疗效的预测价值.方法 对56例乳腺癌患者行TE方案新辅助化疗,应用RT-PCR法检测TE方案化疗前后Survivin、BCRP和HER-2 mRNA的表达差异,并结合化疗疗效进行相关性分析.结果 56例乳腺癌患者经TE方案新辅助化疗后的总有效率为71.4％.全组完全缓解5例,病理完全缓解4例,部分缓解35例,稳定13例,进展3例.Survivin mRNA的阳性表达率由化疗前的60.7％降至化疗后的35.7％ (P =0.008);BCRP mRNA的阳性表达率由化疗前的37.5％降至化疗后的19.6％(P=0.036);HER-2 mRNA的阳性表达率由化疗前的41.1％降至化疗后的21.4％ (P =0.025).Survivin或BCRP单独阴性表达的患者化疗的有效率均较阳性表达者高(均P＜0.05).HER-2 mRNA的单独表达状况与化疗疗效无关(P =0.144).Survivin、BCRP和HER-2 mRNA均为阴性表达的患者化疗疗效高于其他各组(P =0.003).在乳腺癌组织中,Survivin、BCRP和HER-2 mRNA的表达之间不存在相关关系(P＞0.05).结论 联合检测Survivin、BCRP和HER-2的表达可作为预测乳腺癌TE方案新辅助化疗敏感性的分子生物学指标.     

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.     

Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer.

BACKGROUND: The aim of this study was to determine whether expressions of the excision repair cross-complementing (ERCC1), thymidylate synthase (TS), and glutathione S-transferase P1 (GSTP1) predict clinical outcome in patients with advanced gastric cancer treated with fluorouracil (5-fluorouracil)/oxaliplatin chemotherapy. PATIENTS AND METHODS: The study population consisted of 64 advanced gastric cancer patients (median age 51 years). Patients were treated with oxaliplatin 85 mg/m(2) as a 2-h infusion at day 1 plus leucovorin 20 mg/m(2) over 10 min, followed by 5-FU bolus 400 mg/m(2) and 22-h continuous infusion of 600 mg/m(2) at days 1-2. Treatment was repeated in 2-week intervals. The expressions of ERCC1, TS, and GSTP1 of primary tumors were examined by immunohistochemistry. RESULTS: The positive rates of ERCC1, TS, and GSTP1 were 70.3%, 29.7%, and 50.0%, respectively. The patients without ERCC1 expression were more likely to respond to chemotherapy (P = 0.045). There were no significant differences between response and TS or GSTP1 expression pattern (P = 0.813, P = 0.305, respectively). Median overall survival (OS) was significantly longer in patients without ERCC1 expression (P = 0.0396). TS or GSTP1 expression were not related to survival (P = 0.4578, P = 0.8121, respectively). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (hazard ratio 1.92, P = 0.037). CONCLUSION: Immunohistochemical studies for ERCC1 may be useful in prediction of the clinical outcome in advanced gastric cancer patients treated with 5-FU and oxaliplatin.     

Luminal B型局部晚期乳腺癌新辅助化疗疗效预测基因的研究

目的 筛选Luminal B型局部晚期乳腺癌新辅助化疗疗效预测基因。方法 收集10例Luminal B型乳腺癌患者,均行DA方案新辅助化疗（多西他赛 75mg／m2静滴,d1;表阿霉素80mg／m2 静滴d1,21天为1周期,共4个周期）,根据化疗疗效分为完全病理缓解（pCR）组（n=3）和非完全病理缓解（npCR）组（n=7）。采用人基因表达谱cDNA芯片从10例乳腺癌患者中筛选新辅助化疗疗效相关基因,荧光定量PCR验证差异表达基因。结果 pCR组与npCR组癌组织相比,上调基因231个,下调基因195个;pCR组癌组织与癌旁组织相比,上调的基因357个,下调的基因544个;npCR组癌组织与癌旁组织相比,上调基因143个,下调基因101个;pCR组与npCR组癌旁组织比较,上调基因98个,下调基因67个。pCR组与npCR组癌组织比较,筛选出6个与肿瘤有关的基因,其中上调基因为CYP4Z1、FGFL6、BCAR4,下调基因为FABP4、S100B、ALPH1L1。荧光定量PCR进一步验证显示,两组mRNA表达差异的基因为CYP4Z1和BCAR4,pCR组两种基因表达均显著低于npCR组（P＜0.05）。结论 对局部晚期Luminal B型乳腺癌低表达BCAR4和CYP4Z1的患者新辅助治疗选择采用DA方案化疗更有可能获得pCR。     

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.     

Epidermal growth factor receptor expression correlates with poor survival in patients who have breast carcinoma treated with doxorubicin-based neoadjuvant chemotherapy

BACKGROUND: To the authors' knowledge there are few data that correlate the expression of the epidermal growth factor receptor (EGFR) with the outcome of patients who have breast carcinoma and are treated with anthracycline chemotherapy. METHODS: Pretreatment tumor tissue samples were available from 82 patients who had locally advanced breast carcinoma and were treated on 2 protocols investigating neoadjuvant 5-fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Immunohistochemical staining for EGFR (diluted 1:50) was performed, and the staining results were interpreted without knowledge of outcome. RESULTS: Fourteen tumors (17%) were EGFR-positive, and 68 tumors (83%) were EGFR-negative. EGFR expression did not correlate with clinical stage (P = 0.361), HER-2/neu overexpression (P = 0.503), estrogen or progesterone receptor status (P = 0.631 and P = 0.838, respectively), nuclear grade (P = 0.448), or proliferative index (P = 0.769). Patients who had EGFR-positive tumors had a worse 5-year disease-free survival (DFS) rate (46% vs. 76%; P = 0.026) and overall survival (OS) rate (46% vs. 76%; P = 0.037) compared with patients who had EGFR-negative tumors. The pathologic complete response rate did not differ between the 2 groups (P = 0.389), although patients with EGFR-positive disease more commonly had > or = 4 positive lymph nodes after chemotherapy (64% vs. 29%; P = 0.028). EGFR expression continued to show a significant correlation with poorer DFS and OS in a Cox regression analysis model that included the presence or absence of four or more lymph nodes and EGFR status. CONCLUSIONS: EGFR expression may have prognostic significance in patients with locally advanced breast carcinoma who are treated with anthracycline chemotherapy. These data warrant further studies aimed at correlating EGFR expression and outcome in patients who have breast carcinoma treated with doxorubicin-based chemotherapy.     

ERCC1和TS基因多态性在预测顺铂联合5-氟尿嘧啶治疗晚期食管癌疗效中的意义

目的:探讨切除修复交叉互补基因1(excision repair cross-complementation group 1,ERCC1)、胸苷酸合成酶(thymidylate synthase,TS)、谷胱苷肽-S-转移酶P1(glutathione-S-transferase P1,GSTP1)和亚甲酰四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)的基因多态性,在预测顺铂联合5-氟尿嘧啶治疗晚期食管癌疗效中的作用. 方法:107例晚期食管癌患者入组并行顺铂联合5-氟尿嘧啶共3个周期的化疗,最终98例患者按要求完成该治疗且有随访资料.通过测序的方法检测98例患者上述基因位点的多态性,分析基因多态性与化疗客观反应率(response rate,RR)和无进展生存 (progression-free survival,PFS) 期的关系. 结果: ERCC1-C8092A位点A/A或A/C型患者的RR和PFS期优于C/C型患者(P=0.010和P=0.008).TS基因5'端非翻译区(five prime untranslated region,UTR)为2R2R、2R3C或3C3C型患者的RR和PFS期优于2R3G、3C3G或3G3G型患者(P=0.007和P=0.018).GSTP1和MTHFR基因位点的多态性与RR和PFS期无显著相关性.结论:ERCC1-C8092A位点为A/A或A/C型,TS-5'UTR位点为2R2R、2R3C或3C3C型的晚期食管癌患者对顺铂联合5-氟尿嘧啶治疗方案更为敏感.     

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.     

TEM1表达与胃癌患者新辅助化疗疗效相关性研究

  目的  检测胃癌组织中P53、人表皮生长因子受体2（HER-2）、肿瘤内皮标记物1（TEM1）的表达情况,结合新辅助化疗后临床疗效进行相关性分析,探讨其作为新辅助化疗疗效生物学标志物的可能性。  方法  选取2015年5月至2017年5月于兰州大学第一医院就诊以氟尿嘧啶为基础行新辅助化疗的63例胃癌患者,对新辅助化疗前的胃癌标本行免疫组织化学法检测P53、HER- 2、TEM1的表达情况,通过影像学评估新辅助化疗疗效,分析各肿瘤指标与新辅助化疗疗效之间的关系。  结果  63例进展期胃癌患者新辅助化疗后总有效率为69.8%,其中完全缓解（complete response,CR）2例,部分缓解（partial response,PR）7例,疾病稳定（stable disease,SD）35例,疾病进展（progressive disease,PD）19例;单因素分析结果显示TEM1阳性、T分期较高的患者新辅助化疗疗效较差（均P < 0.05）;病变部位、分化程度、病灶大小、P53（P=0.488）阳性及HER-2（P=0.106）阳性表达与胃癌新辅助化疗疗效无相关。多因素分析结果显示TEM1阳性、T分期高可能是进展期胃癌患者新辅助化疗疗效差的预测因素。  结论  TEM1作为肿瘤基质的标志物,其阳性表达可能成为预测胃癌新辅助化疗疗效差的重要分子生物学指标。