Overexpression of survivin mRNA is associated with a favorable prognosis following neoadjuvant radiochemotherapy in esophageal cancer

Survivin is a member of the inhibitor of apoptosis (IAP) gene family known to be involved in resistance to chemo- and radiation therapy. We examined the potential of quantitative survivin mRNA expression to predict histopathologic tumor response and prognosis following neoadjuvant radiochemotherapy (cis-platinum, 5-FU, 36 Gy) in patients with locally-advanced esophageal cancer (cT2-4, Nx, M0). Tumor (T) and normal tissue (N) samples from 51 patients were collected by endoscopic biopsy prior to treatment. Survivin mRNA expression was analyzed by quantitative real-time RT-PCR assays. Histomorphologic regression was defined as a major response when resected specimens contained <10% of residual vital tumor cells or if a pathologically complete response was achieved. Some 7/51 patients had progressive disease and 44/51 proceeded to surgical resection. Of 44 resected tumors, 17 (31.4%) showed a major and 27 (61.4%) showed a minor histopathologic response; the survival rates were significantly different (p<0.01). Median absolute survivin expression was 5.1 in the tumor and 2.4 in corresponding normal tissue samples (Wilcoxon, p<0.001). Median relative (T/N ratio) survivin mRNA expression was 1.7. Survivin mRNA expression levels did not show a significant association with histomorphologic regression. Relative survivin mRNA expression of a T/N ratio >1 indicated a favorable prognosis (log-rank, p<0.003). Expression levels of survivin mRNA in pretherapeutic biopsies did not predict the extent of histomorphologic tumor regression following preoperative radiochemotherapy for esophageal cancer. However, overexpression of survivin mRNA in pretreatment biopsies (T/N ratio >1) was associated with superior survival probabilities.     

对食管癌多重治疗疗效的预测

Patients with locally advanced esophageal cancer have a dismal prognosis when treated exclusively by surgery. This fact prompted many investigators to apply neoadjuvant treatment strategies in an effort to improve survival. Results from phase Ⅲ randomized trials are encouraging however, they revealed that only patients with major histopathological response will benefit from treatment. Therefore, predictive molecular markers indicating response or non-response to neoadjuvant treatment would be extremely helpful in selecting patients for current and future treatment protocols. In this paper we review the role of the molecular markers ERCC1 (excision repair cross-complementing 1 gene) and c-erbB-2 (synonym:HER2/neu) in predicting response to radiochemotherapy and outcome for patients with locally advanced resectable esophageal cancers (cT2-4, Nx, M0). The results are promising and it appears that we might expect to unequivocally identify with ERCC1 and c-erbB-2 respectively, approximately up to one third of patients who fulfil the criteria for neoadjuvant treatment for locally advanced esophageal cancer but will not benefit from our treatment protocol. Integration of such markers in the clinical setting might prevent a substantial number of patients from expensive, non-effective and potentially harmful therapies, and could lead to a more individualized type of combined multimodality treatment in the near future.     

ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients.

BACKGROUND: ERCC1 and ERCC2 are human DNA repair genes that are associated with in vitro resistance to selected DNA-damaging agents. PURPOSE: Fresh tumor tissues from 26 patients with ovarian cancer were analyzed for the RNA levels of expression of these genes to determine possible clinical relevance. METHODS: Tumor tissues were harvested from patients immediately before they entered a cisplatin- or carboplatin-based treatment protocol. Clinical response was assessed by standard criteria. Gene expression level was assessed by slot blot analysis, using beta-actin as a control. Relative expression levels were determined by comparing each tumor sample with a Chinese hamster ovary cell line that had a stable transfection of the human ERCC1 gene. RESULTS: Patients who were clinically resistant to platinum-based therapy had a 2.6-fold higher expression level of ERCC1 in their tumor tissue than did patients who responded to that therapy (P = .015). Results obtained by slot blot analysis were qualitatively confirmed by polymerase chain reaction analysis. Relative levels of expression of ERCC2 did not differ significantly between responders and nonresponders. CONCLUSION: We conclude that ERCC1 expression levels in human tumor tissue may have a role in clinical resistance to platinum compounds. These data appear to be consistent with the assertion that ERCC1 serves as an excision nuclease, whereas ERCC2 serves as a helicase.     

MicroRNA profiling in locally advanced esophageal cancer indicates a high potential of miR‐192 in prediction of multimodality therapy response

To identify possible predictive markers, our study aimed to characterize microRNA (miRNA) profiles of responder and nonresponder in the multimodality therapy of locally advanced esophageal cancer. Initially, a microarray‐based approach was performed including eight patients with esophageal cancer. Patients received neoadjuvant chemoradiation followed by surgical resection. Major histopathological response was defined if resected specimens contained less than 10% vital tumor cells (major/minor response: 4/4 patients). Intratumoral RNA was isolated from both, pretherapeutic tissue biopsies in addition to corresponding surgical specimens. The profile of 768 miRNAs was analyzed in 16 specimens (preneoadjuvant and postneoadjuvant therapy). Selected miRNAs were than analyzed on pretherapeutic and post‐therapeutic biopsies of 80 patients with esophageal cancer, who underwent multimodality therapy (major/minor response: 30/50 patients). Comprehensive miRNA profiling identified miRNAs in pretherapeutic biopsies that were significantly different between major/minor responders. Based on the microarray results, miR‐192, miR‐194 and miR‐622 were selected and the dysregulated miRNAs were studied on an extended series of esophageal cancer patients. The expression of miR‐192, miR‐194 and miR‐622 was significantly reduced after neoadjuvant therapy confirming the array profiling data. Importantly, the pretherapeutic intratumoral expression of miR‐192 and miR‐194 was significantly associated with the histopathologic response of esophageal squamous cell carcinoma to multimodal therapeutic treatment. Therefore, in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation followed by esophagectomy, miR‐192 and miR‐194 in pretherapeutic biopsies are considered as indicators of major histopathologic regression.     

两种新辅助联合方案治疗食管鳞癌30例病理学评估

目的探讨局部晚期食管鳞癌经不同新辅助治疗(新辅助放化疗及新辅助特瑞普利单抗联合放化疗)后, 根治术切除标本之间的组织病理学差异。方法收集2020年10月至2021年9月期间于江苏省肿瘤医院接受新辅助治疗后手术切除食管鳞癌患者30例, 其中行新辅助放化疗者(放化疗组)15例, 行新辅助特瑞普利单抗联合放化疗者(放化免组)15例。收集患者手术标本, 分析并比较两组食管原发灶组织病理学特征及受累淋巴结反应之间的差异。结果放化疗组及放化免组病理显著缓解(MPR)率分别为10/15及14/15(P=0.17), 原发灶病理完全缓解(pCR)率分别为7/15及10/15(P=0.46);出现三级淋巴样结构(TLS)者分别为7/15及12/15(P=0.02), 出现坏死者分别为6/15及1/15(P=0.03), 泡沫样组织细胞出现率分别为6/15及13/15(P=0.01), 受累淋巴结治疗后的pCR率分别为7/33及11/12(P<0.001)。结论相比于放化疗组, 放化免组更容易出现TLS、泡沫样组织细胞聚集, 同时坏死出现的频率更低, 且已受累的淋巴结治疗反应更好, 提示新辅助特瑞普...     

Monitoring of Tumor Response to Neoadjuvant Radio-Chemotherapy of Esophageal Carcinoma by F-18-FDG-PET

Introduction Esophageal carcinoma is an aggressive malignancy. Thelong-term survival of patients with locoregionally advanceddisease treated with surgery alone ranges between 40%and 4% with median times of survival of 9–29 months[1?6].Because of such poor results additional chemotherapy andradiotherapy have been evaluated[7?10]. There is contin-uing discussion under which conditions such multimodaltherapy regimens can mean a bene?t in terms of longersurvival[4,8?11]. A multimodal therapy o…     

ERCC1 mRNA 表达水平与Ⅱ期鼻咽癌顺铂同步放化疗疗效相关性的临床研究

目的：探讨鼻咽癌组织中 DNA 切除修复交叉互补基因1（ERCC1）的 mRNA 表达水平与Ⅱ期鼻咽癌顺铂同步放化疗疗效关系。方法78例初诊经鼻咽肿物活检确诊为鼻咽部低分化鳞癌的Ⅱ期鼻咽癌患者,取患者化疗前肿瘤组织通过 RT-PCR 方法检测其 ERCC1 mRNA 表达水平,患者均接受顺铂同步放化疗。通过 RECIST 11实体瘤疗效评定标准评定近期疗效,分析 ERCC1 mRNA 表达水平与近期疗效的关系。结果78例患者均可评价疗效,有效率为8974%,疾病控制率为9487%。Ⅱ期鼻咽癌组织中 ERCC1 mRNA的中位数水平为1119。化疗前Ⅱ期鼻咽癌组织中 ERCC1 mRNA 的表达水平与治疗后的近期疗效有显著相关性（P ＜005）。结论 ERCC1 mRNA 表达水平对Ⅱ期鼻咽癌顺铂同步化疗疗效及预后有一定的预测价值。     

ERCC1 mRNA表达与恶性胸腹腔积液肿瘤细胞对顺铂体外药敏相关性的研究

目的：分析切除修复交叉互补基因l（excision repair egoS8 complementafion group 1,ERCC1）在恶性胸腹腔积液肿瘤细胞中的表达,探讨ERCC1 mRNA表达与患者顺铂耐药的相关性.方法：收集26例经病理确诊的恶性胸腹腔积液,分离原代肿瘤细胞,CCK8体外药物敏感性试验检测顺铂对原代肿瘤细胞的抗肿瘤作用,荧光定量RT-PCR检测细胞中药物疗效相关基因ERCC1的相对表达水平.结果：ERCCI mRNA在恶性胸腹腔积液原代肿瘤细胞中的表达水平与临床特征无相关性,但与顺铂敏感件呈负相关,低表达者对顺铂敏感性高（P=0.01）.结论：ERCC1 mRNA表达水平可以作为预测转移性胸腹腔积液患者铂类药物化疗疗效的指标之一.     

Platinum-sensitive and platinum-resistant ovarian cancer tissues show differences in the relationships between mRNA levels of p53, ERCC1 and XPA

We investigated the association between p53 mRNA expression and clinically relevant surrogates of nucleotide excision repair (ERCC1 and XPA) in 28 ovarian cancer specimens. We observed that platinum-resistant tumors showed higher mRNA levels of p53, ERCC1, and XPA than platinum-sensitive tumors; mRNA expression patterns in responders differed substantially from nonresponders; and p53 expression showed a strong correlation with the expression of ERCC1, and of XPA in platinum-sensitive tumor tissues, but not with platinum-resistant tumors. 47% of the mutations from p53 sequence analysis were not related to clinical response to chemotherapy. We conclude that the p53 influence on DNA repair in human malignancy may vary substantially from tumor to tumor, and that such differences are not necessarily related to the mutational status of p53.     

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.