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1.
Platinum-based chemotherapies are widely used in the treatment of lung cancer. However, little is known about their effect in the expression of certain tissue biomarkers. We have studied the ERCC1 (excision repair cross-complementation group 1) expression in tissue samples of patients treated with neoadjuvant chemotherapy. Fifty lung cancer tissue blocks of 25 patients (15 males, 10 females) were studied. They included 25 bronchoscopic biopsies (14 squamous cell carcinomas and 11 adenocarcinomas) together with their corresponding surgical biopsies after neoadjuvant chemotherapy. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded tissues to study the expression of ERCC1. Staining scores (0-300) were calculated by multiplying the percentage of positive tumor cells (0-100) by the staining intensity (0-3). All but one bronchosopic squamous cell carcinoma tissues (13/14) expressed ERCC1. Four of these cases became negative after neoadjuvant therapy, and in 8 cases the level of expression decreased. In the adenocarcinoma group all but one bronchosopic tissues (10/11) expressed ERCC1. Six of these cases became negative after neoadjuvant therapy, and in 4 cases the level of expression decreased. Comparison of staining scores before and after chemotherapy revealed more pronounced decrease in adenocarcinomas and in female patients. There was no newly expressed ERCC1-positive case in the surgical biopsy group. The results of the present study suggest that platinum-based chemotherapy affects the expression of tissue biomarker (ERCC1) which may have predictive value, and probably induces a selection of tumor cells with more aggressive phenotype. This knowledge might be of importance when designing treatment protocols for non-small cell lung cancer patients.  相似文献   

2.
Gallbladder cancer (GBC) is the main cause of death by malignant tumour in women in Chile. There is no information regarding the role of excision repair cross-complementing group 1 (ERCC1) in GBC. Our aim is to determine the expression and significance of ERCC1 as a prognostic factor in GBC. Tissue microarrays were prepared using 200 surgically resected GBCs and 50 non-malignant gallbladders as controls. In 190 cases, ERCC1 was determined by immunohistochemistry. The correlation between ERCC1 expression and GBC pathological characteristics and patient survival were analysed. Ninety-five percent of the non-malignant gallbladder epithelia showed intense and diffuse ERCC1 expression. GBC cases showed ERCC1 expression in the tumour cells in 100/190 (53%) cases. The best differentiated tumours showed significantly greater expression than the less differentiated (p<0.05). Patients with ERCC1-positive status with subserosal carcinomas (pT2) had significantly better survival than ERCC1-negative patients at 20 and 60 months of follow-up (p=0.005), and the probability of dying was 6 times lower for ERCC1-positive than for ERCC1-negative patients. Our preliminary results show that chole-cystectomised patients with GBC in stage pT2 and with ERCC1 expression have significantly better survival than patients at the same stage that did not present ERCC1 expression.  相似文献   

3.
Esophageal carcinoma is one of the world''s deadliest cancers. Esophageal squamous cell carcinoma (ESCC) is more frequent than adenocarcenoma (AC) in China. Platinum-based chemotherapy with surgical resection is a common treatment approach for ESCC; however, the treatment response is uncertain. Evidence suggests polymorphisms in genes encoding excision repair cross-complementing group 1 (ERCC1), a protein involved in nuclear excision repair (NER), may help predict response to cisplatin and other platinum-based chemotherapeutics. Multiple ERCC1 single nucleotide polymorphisms (SNPs) have been associated with platinum chemotherapy response. Two common SNPs occur at the C8092A and C118T loci. Our study aimed to determine if 1) an association exists between ERCC1 tumor expression and patient survival, 2) whether adjuvant therapy influence on survival is related to histological ERCC1 presence in tumor cell nuclei, and 3) whether other clinicopathological characteristics in a cohort of patients following surgery for various stages of ESCC are associated with tumor ERCC1 expression. One hundred eight patients were included in the study, and tumor biopsy was collected for genotyping and immunohistochemical analysis of ERCC1. Sixty-seven patients (62%) received no adjuvant therapy, and the rest had either platinum-based chemotherapy (28.5%), radiotherapy (6.5%) or both treatments (2.8%). Log-rank analysis revealed no significant connection between tumor ERCC1 expression (P = 0.12) or adjuvant therapy (P = 0.56) on patient survival. Also, non-parametric Mann-Whitney analysis showed no significant link between tumor size or nodus tumor formation and ERCC1 presence in patients in the study. Interestingly, C8092A SNP showed significant association with patient survival (P = 0.01), with patients homozygous for the mutant allele showing the most significantly reduced survival (P = 0.04) compared to those homozygous for the dominant allele (CC). Our results provide novel insight into the genotypic variation of patients from Quanzhou, Fujian province China.  相似文献   

4.
目的:探讨卵巢癌组织切除修复交叉互补基因(ERCC1)、波形蛋白(Vimentin)表达与临床病理特征及预后的关系。方法:选取2015年3月~2016年2月期间首都医科大学附属北京世纪坛医院收治的卵巢癌患者83例为研究对象,收集每位患者的卵巢癌组织样本、癌旁正常组织样本,采用免疫组化SP法对各组织标本中的ERCC1、Vimentin的阳性表达率、表达水平进行检测,并分析ERCC1、Vimentin表达与卵巢癌临床病理特征间的关系,并对患者进行统一的手术治疗,分析ERCC1、Vimentin阳性表达组与阴性表达组患者的预后。结果:卵巢癌组织的ERCC1、Vimentin的阳性表达率分别为54.22%(45/83)、69.88%(58/83),高于癌旁正常组织的9.64%(8/83)、20.48%(17/83),差异有统计学意义(P0.05)。卵巢癌组织的ERCC1、Vimentin的表达水平均高于癌旁正常组织(P0.05)。ERCC1、Vimentin的阳性表达率与卵巢癌患者的年龄、病灶直径、病理分型无关,而与卵巢癌肿瘤的临床分期、分化程度、淋巴结转移有关。ERCC1、Vimentin阳性表达组患者的无进展生存期(PFS)、总体生存期(OS)均短于ERCC1、Vimentin阴性表达组(P0.05)。结论:ERCC1、Vimentin的表达水平与卵巢癌的分期、分化程度、淋巴结转移有关,在卵巢癌的发生发展过程中起重要作用,ERCC1、Vimentin可能作为卵巢癌患者预后评估的参考指标。  相似文献   

5.
目的:研究晚期非小细胞肺癌不同的p53和ERCC1表达状态与基于顺铂为主的姑息化疗近期有效率的相关性。方法:对经顺铂联合多西他赛或顺铂联合吉西他滨治疗的48例晚期非小细胞肺癌患者进行回顾性分析,利用既往免疫组化资料,观察基于顺铂为主的方案近期有效率(RR)的影响因素及化疗不良反应。结果:全组48例患者均完成至少两周期化疗,并行疗效评价。该组患者化疗的近期有效率为28例(58.3%),RR与不同的转移病灶部位(P=0.042)及病灶数目(P=0.034)有显著差异。该类方案的近期有效率与ERCC1状态(P=0.012)密切相关,而与p53表达状态(P=0.401)无关。毒性反应主要是骨髓抑制、脱发及消化道反应等。结论:晚期非小细胞肺癌ERCC1阴性患者较ERCC1阳性患者运用顺铂为主的联合方案化疗的近期有效率较高。ERCC1可能是顺铂疗效预测的敏感因子。p53的表达状态可能不是该类方案的疗效预测因子。  相似文献   

6.
目的:观察非小细胞肺癌中ERCC1和RRM1表达,并探讨其临床意义。方法:选择本院及西安交通大学第一附属胸外二科于2013年1月-2013年6月收治的经术后病理证实为非小细胞癌肺癌患者40例作为研究对象,均采取免疫组化技术测定组织中ERCC1和RRM1表达水平,并分析ERCC1和RRM1表达水平与患者年龄、病理分期、是否淋巴结转移等相关因素之间的关系。结果:40例非小细胞肺癌患者中,ERCC1表达阴性28例(70.0%),阳性12例(30.0%);RRM1表达阴性9例(22.5%),阳性31例(77.5%)。ERCC1和RRM1表达阴性非小细胞肺患者生存期均优于表达阳性患者,均P0.05。患者非小细胞癌TNM分期及淋巴结转移转移情况与ERCC1及RRM1表达情况具有相关性,均P0.05。结论:非小细胞肺癌ERCC1和RRM1表达水平测定有助于预后情况,具有重要临床价值。  相似文献   

7.
Because of the variability of the structural features of cerebral tumors, the characteristics observed in biopsy samples may not be representative of the whole neoplasm. The reliability of cerebral stereotactic biopsy is therefore greatly debated. In order to test the value of diagnoses based on biopsy samples, the authors compared histological and cytological data obtained from a small fragment of a tumor with the definitive diagnosis obtained from surgical or necropsy specimens. An analysis of 64 cases is reported, where a correct diagnosis from the biopsy sample was achieved in 92.2% of the cases. Neuroglial tumors were more difficult to characterize than other types of intracranial tumors, with an accuracy of 81.5%.  相似文献   

8.
In a series of more than 2,500 fine needle aspirates from multiple body sites, over 200 were clinically identified as lymph nodes from patients with known or suspected malignancy. The material was obtained using the easily manipulated Aspir-Gun with a 21-gauge or 22-gauge needle and syringe. Of the 200 lymph node specimens, 100 (50%) were cytologically reported as positive for malignancy. Ninety cases had surgical pathology specimens available for comparison with the fine needle aspiration (FNA) specimens. For the 88 of these cases with satisfactory FNA specimens, evaluation of the FNA results showed a predictive value of a positive result of 96.8%. These results compare favorably with those of surgical biopsy. The malignancies present in the lymph nodes included numerous adenocarcinomas from the breast, melanoma and pulmonary small-cell carcinoma. Six cases are briefly presented in which the FNA diagnosis was more problematic. While histologic examination of tissues or organs remains the desirable benchmark of comparison, the appropriate utilization of FNA cytology to guide therapy, particularly in a patient with previously diagnosed malignancy, may obviate the need for an open biopsy. The technique is convenient for patient and physician, useful for outpatients, relatively painless and provides good correlation between cytologic morphology and histopathology.  相似文献   

9.
Six hundred and two mammary tumors were examined clinically, by mammography and cytology, with a histologic checkup following surgical biopsy. There were 247 cases of malignoma and 355 benign cases. The limited reliability of the individual methods is demonstrated, and it is shown that their combined use can improve the diagnosis. More malignomas are detected, and preoperative diagnosis is made more safely. If all three methods yield identical results, as was the case in 50.2% of the malignant and 32.7% of the benign lesions, the probability of diagnostic error is less than one per cent. With a malignoma thus established, surgical treatment may follow immediately, or irradiation can be started. In benign cases a surgical biopsy may be foregone and further developments may be awaited with due provision for regular control. If the three methods yield conflicting or doubtful results, elucidation by surgical biopsy and histology is indicated.  相似文献   

10.
OBJECTIVE: To determine whether various methods of fixation of surgical pathology specimens from breast carcinomas would influence the outcome of evaluation of the expression levels of c-erbB-2 (HER-2). For this, comparisons were made between (1) alcohol-fixed (95%) and air-dried smears from fresh surgical pathology specimens of breast carcinomas, and (2) formalin-fixed, paraffin-embedded tissue sections of the same specimens. STUDY DESIGN: Alcohol-fixed and air-dried smears or touch preparations were made from 30 fresh mastectomy/lumpectomy surgical pathology specimens from breast carcinomas. Immunohistochemistry was performed using the c-erbB-2 primary antibody against the extracellular domain of the c-erbB-2 gene product. Staining was simultaneously performed on formalin-fixed, paraffin-embedded tissue sections of the same specimens. A semiquantitative approach was used for evaluation of immunostaining by three independent investigators, and a consensus was reached. RESULTS: A total of 30 cases were reviewed. Tissue positivity was determined for c-erbB-2 in: 73% of alcohol-fixed specimens (n = 13 [3+] and n = 9 [2+]), 67% of air-dried smears (n = 9 [+3] and n = 11 [+2]) and 47% (n = 8 [+3]) and n = 6 [+2]) of formalin-fixed, paraffin-embedded tissue specimens. All formalin-fixed tissue specimens that were determined to positively express c-erbB-2 were also found to be positive on the alcohol-fixed smears. CONCLUSION: The incidence of c-erbB-2 expression in fresh cytologic material is significantly higher (P < .05) than in formalin-fixed, paraffin-embedded tissue. Alcohol-fixed smears demonstrate a slightly higher percentage of cell staining and stronger intensity of c-erbB-2 expression than the matched, air-dried smears. This is a sensitive and simple processing method that can be routinely applied in surgical pathology or fine needle aspiration biopsy specimens for the detection of c-erbB-2 (HER-2), with clinical implications.  相似文献   

11.
Excision Repair Cross-Complementing Group 1 (ERCC1) is an important DNA repair gene, playing critical role in nucleotide excision repair pathway and having a significant influence on genomic instability. Some studies support that ERCC1 might be a potential predictive and prognostic marker in non-small cell lung cancer (NSCLC). ERCC1 has also been shown to be a promising biomarker in NSCLC treated with a cisplatin-based regimen. Therefore, the determination of ERCC1 expression at DNA, mRNA and protein level in different stages of NSCLC is still an important topic in the cancer. Ninety-one formalin-fixed paraffin-embedded tumor samples histopathologically diagnosed as NSCLC were examined in this study. ERCC1 expression at protein level were scored by immunohistochemistry. The gene amplification and mRNA expression levels for ERCC1 were determined by real-time quantitative PCR. There was complete concordance among the three methods in 39 tumor samples (42.9%). A strong correlation was found between DNA amplification and mRNA expression (r = 0.662) while there was no correlation between mRNA and protein assessment for ERCC1 expression (r = −0.013). ERCC1 expression at mRNA and DNA level (63.1 and 84.2%, respectively) in tumors at stage III was higher than at the other stages. In contrast, the protein expression at stage II and III (56.6 and 52.6%, respectively) of NSCLC was lower than that of tumors with stage I NSCLC. These results show that the mechanism by which ERCC1 expression might play a role in tumor behavior. This study was also confirmed that the appropriate validation and qualification in methods used for ERCC1 status were needed before its clinical application and implementation.  相似文献   

12.
In carcinogenesis, the "field defect" is recognized clinically because of the high propensity of survivors of certain cancers to develop other malignancies of the same tissue type, often in a nearby location. Such field defects have been indicated in colon cancer. The molecular abnormalities that are responsible for a field defect in the colon should be detectable at high frequency in the histologically normal tissue surrounding a colonic adenocarcinoma or surrounding an adenoma with advanced neoplasia (well on the way to a colon cancer), but at low frequency in the colonic mucosa from patients without colonic neoplasia.Using immunohistochemistry, entire crypts within 10 cm on each side of colonic adenocarcinomas or advanced colonic neoplasias were found to be frequently reduced or absent in expression for two DNA repair proteins, Pms2 and/or ERCC1. Pms2 is a dual role protein, active in DNA mismatch repair as well as needed in apoptosis of cells with excess DNA damage. ERCC1 is active in DNA nucleotide excision repair. The reduced or absent expression of both ERCC1 and Pms2 would create cells with both increased ability to survive (apoptosis resistance) and increased level of mutability. The reduced or absent expression of both ERCC1 and Pms2 is likely an early step in progression to colon cancer.DNA repair gene Ku86 (active in DNA non-homologous end joining) and Cytochrome c Oxidase Subunit I (involved in apoptosis) had each been reported to be decreased in expression in mucosal areas close to colon cancers. However, immunohistochemical evaluation of their levels of expression showed only low to modest frequencies of crypts to be deficient in their expression in a field defect surrounding colon cancer or surrounding advanced colonic neoplasia.We show, here, our method of evaluation of crypts for expression of ERCC1, Pms2, Ku86 and CcOI. We show that frequency of entire crypts deficient for Pms2 and ERCC1 is often as great as 70% to 95% in 20 cm long areas surrounding a colonic neoplasia, while frequency of crypts deficient in Ku86 has a median value of 2% and frequency of crypts deficient in CcOI has a median value of 16% in these areas. The entire colon is 150 cm long (about 5 feet) and has about 10 million crypts in its mucosal layer. The defect in Pms2 and ERCC1 surrounding a colon cancer thus may include 1 million crypts. It is from a defective crypt that colon cancer arises.  相似文献   

13.

Background

Single nucleotide polymorphisms (SNPs) in DNA repair genes can alter gene expression and activity and affect response to cancer treatment and, correspondingly, survival. The present study was designed to evaluate the utility of the XRCC1 Arg399Gln and ERCC1 Cys8092Ala SNPs, measured in pretreatment biopsy samples, as predictors of response to radiotherapy in patients with non-metastatic nasopharyngeal carcinoma (NPC).

Materials and methods

The study included 75 consecutive patients with stage II-IVA-B NPC. XRCC1 Arg399Glu and ERCC1 Cys8092Ala SNPs were identified from paraffin-embedded biopsy specimens via Sanger sequencing. Expression of p53 and pAkt protein was analyzed by immunohistochemical staining. Potential relationships between genetic polymorphisms and progression-free survival (PFS) were analyzed by using a Cox proportional hazards model, the Kaplan-Meier method, and the log-rank test.

Results

Multivariate analysis showed that carriers of the ERCC1 8092 Ala/Ala genotype [hazard ratio (HR) 1.882; 95% confidence interval (CI) 1.031–3.438; P = 0.039] and heavy smokers (≥20 pack-years) carrying the XRCC1 Arg/Arg genotype (HR 2.019; 95% CI 1.010–4.036; P = 0.047) had significantly lower PFS rates. Moreover, combined positive expression of p53 and pAkt led to significantly increased PFS in subgroups carrying the XRCC1 Gln allele (HR 7.057; 95% CI 2.073–24.021; P = 0.002) or the ERCC1 Cys allele (HR 2.568; 95% CI 1.056–6.248; P = 0.038).

Conclusions

The ERCC1 Cys8092Ala polymorphism is an independent predictor of response to radiotherapy for NPC, and the XRCC1 Arg399Glu mutation combined with smoking status seems to predict PFS as well. Our results further suggest a possible correlation between these genetic polymorphisms and p53 protein status on survival.  相似文献   

14.
MicroRNAs are deemed as key regulators of gene expression. In particular, the elevated expression of excision repair cross-complementing 1 (ERCC1) significantly reduced the effectiveness of gastric cancer treatment by cisplatin (CDDP)-based therapies. In this paper, qRT-PCR and western blot were adopted to measure miR-122 and ERCC1 messenger RNA (mRNA) expression in all samples. Luciferase assay was carried out to verify the role of ERCC1 as a target of miR-122. The CCK-8 assay was carried out to study the effect of ERCC1 and miR-122 on cell survival and apoptosis. The results demonstrated that miR-122 expression was reduced in cisplatin-resistant gastric cancer. Using bioinformatic analysis, miR-122 was shown to target the 3′-UTR of human ERCC1. A dual-luciferase assay demonstrated that miR-122 downregulated ERCC1 expression, while the mutations in ERCC1 3′-UTR abolished its interaction with miR-122. Transfection of miR-122 mimics decreased the levels of ERCC1 mRNA and protein expression, while the transfection of miR-122 inhibitors increased the levels of both ERCC1 mRNA and protein expression. Furthermore, we found that overexpressed miR-122 promoted the proliferation of MKN74 cells and reduced their apoptotic by targeting ERCC1. In addition, the levels of miR-122 and ERCC1 were negatively correlated in gastric cancer samples. In summary, the reduced miR-122 expression may play an essential role in the induction of cisplatin-resistance by increasing ERCC1 expression.  相似文献   

15.

Purpose

The Ki-67 labelling index is significant for the management of breast cancer. However, the concordance of Ki-67 expression between preoperative biopsy and postoperative surgical specimens has not been well evaluated. This study aimed to find the correlation in Ki-67 expression between biopsy and surgical specimens and to determine the clinicopathological risk factors associated with discordant values.

Patients and Methods

Ki-67 levels were immunohistochemically measured using paired biopsy and surgical specimens in 310 breast cancer patients between 2008 and 2013. ΔKi-67 was calculated by postoperative Ki-67 minus preoperative levels. The outliers of ΔKi-67 were defined as [lower quartile of ΔKi-67–1.5 × interquartile range (IQR)] or (upper quartile + 1.5 × IQR) and were evaluated according to clinicopathological parameters by logistic regression analysis.

Results

The median preoperative and postoperative Ki-67 levels were 10 (IQR, 15) and 10 (IQR, 25), respectively. Correlation of Ki-67 levels between the two specimens indicated a moderately positive relationship (coefficient = 0.676). Of 310 patients, 44 (14.2%) showed outliers of ΔKi-67 (range, ≤-20 or ≥28). A significant association with poor prognostic factors was found among these patients. Multivariate analysis determined that significant risk factors for outliers of ΔKi-67 were tumor size >1 cm, negative progesterone receptor (PR) expression, grade III cancer, and age ≤35 years. Among 171 patients with luminal human epidermal growth factor receptor 2-negative tumors, breast cancer subtype according to preoperative or postoperative Ki-67 levels discordantly changed in 46 (26.9%) patients and a significant proportion of patients with discordant cases had ≥1 risk factor.

Conclusion

Ki-67 expression showed a substantial concordance between biopsy and surgical specimens. Extremely discordant Ki-67 levels may be associated with aggressive tumor biology. In patients with luminal subtype disease, clinical application of Ki-67 values should be cautious considering types of specimens and clinicopathological risk factors.  相似文献   

16.
This study was carried out to assess how reliably a punch biopsy of the cervix predicts the maximum grade of CIN present and whether a colposcopically directed punch biopsy is more reliable than cytology in predicting the grade of intraepithelial neoplasia present in the cervix. The grade of CIN in 107 cone biopsy specimens was compared with the grade of CIN and dyskaryosis in punch biopsies and smears from the same patients. Exact correlations were identified between the highest grade lesions on cone biopsy and those in 63% of punch biopsies and 49% of cervical smears. fie conclude that punch biopsy provides a more reliable estimate of the highest grade of CIN present in a subsequent cone biopsy than cervical cytology, but nonetheless fails to give a consistent estimate of the final grade of CIN in a significant percentage of cases.  相似文献   

17.
Because the molecular mechanisms underlying the development of laryngeal cancer are not well understood, we conducted a case–control study to determine the association between eight common SNPs in NER pathway genes and risk of laryngeal cancer, and the association between genetic polymorphisms and environmental factors. A 1:1 matched case–control study of 176 cases and 176 controls was conducted. Laryngeal cancer cases were more likely to smoke and drink (all P values < 0.05). Subjects with the ERCC1 rs11615 CC genotype and C allele had an increased risk of laryngeal cancer. Similarly, individuals with the ERCC5 rs17655 GG genotype and G allele had an increased risk of laryngeal cancer. Gene–gene interaction analysis showed that subjects carrying ERCC1 rs11615 C allele and XPG/ERCC5 rs17655 G allele had a greatly increased risk of breast cancer. Stratified analysis revealed that the interaction between polymorphisms of ERCC1 rs11615 and ERCC5 rs17655 and smoking on cancer risk was statistically significant, and ERCC1 rs11615 polymorphisms also had a significant interaction with drinking habit. In conclusion, our study suggests that ERCC1 rs11615 and ERCC5 rs17655 polymorphisms are associated with increased risk of laryngeal cancer, and that they confer more risk among smokers and drinkers.  相似文献   

18.
19.
顾术东  张曙  刘艳  刘凡  茅国新 《生物磁学》2013,(36):7017-7020
目的:探讨晚期结肠癌癌组织中核苷酸切除修复交叉互补基因1(excisionrepaircross—complementinggenel,ERCCl)~O表达状况及其与患者临床病理特征、奥沙利铂方案化疗疗效及预后之间的关系。方法:采用免疫组化方法检测晚期结肠癌癌组织中ERCCl蛋白表达状况。结果:晚期结肠癌癌组织中ERCCl表达阳性表达率为45.1%。ERCCl蛋白的表达状况与患者的性别、年龄、肿瘤部位、分化程度及病理类型均无关(P〉0.05)。ERCCl蛋白表达阴性患者奥沙利铂方案化疗有效率为56.O%高于表达阳性患者的34.1%(P。0.037),并且接受化疗后表达阴性患者中位生存期为19个月高于表达阳性患者的14个月(P=0.016)。结论:ERCCl蛋白表达阴性的晚期结肠癌患者接受奥沙利铂方案化疗有效率较阴性患者高并有生存受益,ERCCl的表达状态可作为晚期结肠癌化疗方案的选择及预后判断的指标。  相似文献   

20.
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