Survival impact of capsule rupture in stage I clear cell carcinoma of the ovary in comparison with other histological types

Objective

We analyzed a large number of stage I clear cell carcinoma of the ovary (CCC) patients to estimate the survival impact of the capsule status in stage I CCC patients, particularly in comparison with non-CCC patients.

Methods

Clinicopathologic data on 564 patients with stage I epithelial ovarian cancer (EOC) collected under the central pathological review system were subjected to uni- and multivariable analyses to evaluate the disease-free survival (DFS) and overall survival (OS).

Results

There was no significant difference in both the OS and DFS of CCC patients between IA and IC(ir) (intraoperative capsule rupture) {IA vs. IC(ir); OS: P = 0.1402, DFS: P = 0.2701}. In contrast, CCC patients at IC(non-ir) {IC excluding for IC(ir), such as preoperative capsule rupture, positive ascites/washing, and surface involvement} showed a poorer OS and DFS than those at IC(ir), or those at the corresponding stage in non-CCC. In multivariable analysis, the capsule status was an independent prognostic factor of a poor OS and DFS {OS: HR, 2.832; 95% CI 1.156-6.938; P = 0.023; DFS: HR, 4.327; 95% CI, 1.937-9.667; P = 0.0004)} {In contrast, non-CCC: N.S. (OS/DFS)}. Furthermore, in CCC patients, intraperitoneal recurrences were more frequently observed in IC(non-ir) CCC than IA or IC(ir) CCC (P = 0.0083) {In contrast, non-CCC: N.S.}.

Conclusion

This study suggests that CCC patients other than those with intraoperative capsule rupture show a considerable risk for mortality despite adjuvant chemotherapy.     

Role of genotype-based approach in the clinical management of adult acute myeloid leukemia with normal cytogenetics

Acute myeloid leukemia (AML) is the most common form of acute leukemia affecting adults. Although it is a complex disease driven by numerous genetic and epigenetic abnormalities, nearly 50% of patients exhibit a normal karyotype (CN-AML) with an intermediate cytogenetic risk. However, a widespread genomic analysis has recently shown the recurrence of genomic aberrations in this category (mutations of FLT3, CEBPA, NPM1, RUNX1, TET2, IDH1/2, DNMT3A, ASXL1, MLL and WT1) thus revealing its marked genomic heterogeneity. In this perspective, a global gene expression analysis of AML patients provides an independent prognostic marker to categorize each patient into clinic-pathologic subgroups based on its molecular genetic defects. Consistently such classification, taking into account the uniqueness of each AML patient, furnishes an individualized treatment approach leading a step closer to personalized medicine. Overall the genome-wide analysis of AML patients, by providing novel insights into biology of this tumor, furnishes accurate prognostic markers as well as useful tools for selecting the most appropriate treatment option. Moreover it provides novel therapeutic targets useful to enhance efficacy of the current anti-AML therapeutics. Here we describe the prognostic relevance of such new genetic data and discuss how this approach can be used to improve survival and treatment of AML patients.     

Multidrug resistance-associated protein 3 confers resistance to chemoradiotherapy for rectal cancer by regulating reactive oxygen species and caspase-3-dependent apoptotic pathway

This study aimed to clarify the role of multidrug resistance-associated protein 3 (MRP3) in resistance to neoadjuvant chemoradiotherapy and long-term prognosis of advanced rectal cancer. Immunohistochemistry was used to measure MRP3 expression in biopsy specimens of 144 stage II–III rectal cancer patients who received preoperative chemoradiotherapy. The effect of MRP3 expression on short-term pathological response and postoperative long-term prognosis were assessed using the Cox proportional hazards model. Short interfering RNAs targeting MRP3 were synthesized and used to transfect human colorectal carcinoma cell lines. The effect of MRP3 down-regulation on cell proliferation and apoptosis in response to 5-fluorouracil and/or irradiation were examined in vitro and in xenograft mouse models, respectively. The content of intracellular reactive oxygen species and the activity of caspase-3-dependent apoptotic pathway in response to irradiation were further evaluated. High expression (immunoreactive score > 6) of MRP3 significantly predicted poor pathological response to chemoradiotherapy (tumor regression grade ≤ 2 vs. ≥3, p = 0.002) in univariate analysis and unfavorable long-term prognosis (5-year overall survival: HR = 1.612, 95% CI, 1.094–2.375, p = 0.016; 5-year disease-free survival: HR = 1.513, 95% CI, 1.041–2.200, p = 0.030) in multivariate Cox analysis. MRP3 down-regulation significantly increased 5-fluorouracil or irradiation-induced cell apoptosis and attenuated tumor growth following irradiation in animal models. MRP3 inhibition significantly reduced intracellular reactive oxygen species exporting from cells following irradiation, and increased expression of cleaved poly ADP-ribose polymerase and caspase-3. Aberrant expression of MRP3 in rectal cancer confers chemo-radioresistance. MRP3 might be a predictive factor and an attractive target in treating advanced rectal cancer.     

A systematic review of dual targeting in HER2-positive breast cancer

Background

Human epidermal growth factor receptor 2 (HER2) is overexpresed in 15–20% of all breast cancers. Treatment with trastuzumab has led to an improved outcome and prolonged survival of HER2-positive breast cancer patients and today the drug is established as standard of care in both the adjuvant and metastatic settings. However, trastuzumab resistance is common and a major focus in the treatment of HER2-positive breast cancer has been developing therapeutic agents to either potentiate the effect of trastuzumab or to target cells which have become resistant to trastuzumab. The present review addresses efficacy and toxicity of dual targeting in HER2-positive breast cancer.

Materials and methods

A computer-based literature search was carried out using PubMed; data reported at international meetings and clinicaltrials.gov was included.

Results

This paper describes efficacy and safety of lapatinib, pertuzumab or trastuzumab-DM1 in combination with trastuzumab in the (neo)adjuvant and metastatic settings. Furthermore, combinations of trastuzumab and drugs targeting the downstream pathway are described.

Conclusion

Dual blockade is likely to represent a substantial advance for patients with HER2-positive breast cancer. However, the relevant subpopulation remains to be defined and side effects including cardiotoxicity might be a limiting factor to the use. There is an urgent need for prospective biomarker-driven trials to identify patients for whom dual targeting is cost-effective.     

Prognosticators and the role of lymphadenectomy in uterine leiomyosarcomas

Objective  To analyze prognostic factors, the role of lymphadenectomy and postoperative adjuvant treatments in patients with uterine leiomyosarcomas (LMS). Study design  Sixty-three patients with uterine LMS are retrospectively analyzed with respect to both DFS and OS. Results  Multivariate DFS analysis revealed percentage necrosis to be the unique factor to be significant (median DFS was 3.31 years for <25% necrosis and 0.78 for >25% necrosis). Multivariate analysis revealed the mitotic counts to be the unique significant factor affecting the OS (median OS was 7.20 and 1.73 years, respectively, for patients with mitotic counts of 1–5 and >6; respectively). Median DFS was 2.51 years for patients who had undergone lymphadenectomy and 2.36 years for remaining who did not have a lymphadenectomy procedure (P = 0.4). With respect to OS, median values were 2.44 and 3.16 years, respectively (P = 0.7). Number of the resected lymph nodes was also not significant for both OS and DFS. Conclusions  Mitotic counts and percentage necrosis have significant effects on OS and DFS; respectively. Neither the performance nor the extent of lymphadenectomy has an effect on patient survival.     

HIF1A可作为乳腺癌的预后标志物且与免疫细胞浸润相关

目的：借助多种癌症生物信息数据库研究乳腺癌组织中缺氧诱导因子1亚基α(HIF1A)的表达水平及其与乳腺癌患者预后及肿瘤免疫细胞浸润的关系。方法：利用Oncomine、人类蛋白质图谱、基因表达谱交互式分析（GEPIA）及TCGA数据库分析HIF1A基因在乳腺癌组织中的表达及其与患者预后、临床病理特征的关系,并在中国人乳腺癌组织标本（选用2011年1月至2015年12月中国武汉大学人民医院手术切除的93例乳腺癌组织和14例良性乳腺疾病组织）中进行验证。对HIF1A高低表达组间的差异基因进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析,用Cibersort R软件评估HIF1A高低表达样本中免疫细胞浸润丰度差异。结果：生物信息数据显示,HIF1A在乳腺癌组织中高表达,预示着患者DFS预后更好（P<0.05）。HIF1A的表达与雌激素受体（ERP）、孕激素受体（PR）和人表皮生长因子受体2(HER2)表达相关（均P<0.05）。GO生物功能及KEGG通路富集分析结果提示,HIF1A可能参与肿瘤免疫调节等生物活动。使用Cibersort分析结果显示,HIF1A与肿瘤...     

大肠癌组织中ERCC1、TS表达及临床意义

目的：探讨ERCC1和TS蛋白在大肠癌中的表达及其临床意义。方法：采用免疫组化SP法和组织芯片对196例大肠癌组织和50例正常大肠切缘组织进行ERCC1和TS蛋白表达水平检测,分析两者与临床病理特征的关系。其中129例术后患者行FOLFOX4方案化疗,随访3年。结果：在结直肠癌中ERCC1及TS表达均高于正常肠黏膜组织,而与性别、年龄、分化程度、部位无关（P〉0.05）,TS阳性表达率及两者双阳性表达率均在有淋巴结转移者及TNMⅢ期、Ⅳ期患者中明显升高。ERCC1、TS阴性表达者3年DFS均分别高于阳性表达者（P〈0.05）。结论：ERCC1和TS蛋白在大肠癌中的阳性表达较高,可能与肿瘤的发生、转移有关。ERCC1和TS蛋白阴性者可从FOLFOX4化疗中获益。     

术前NLR和PLR对上皮性卵巢癌患者预后的评估价值

目的:探讨术前中性粒细胞与淋巴细胞比值(NLR)和血小板与淋巴细胞比值(PLR)对上皮性卵巢癌患者预后的评估价值。方法:收集2005年11月至2012年12月在天津市中心妇产科医院初治且经手术治疗的153例卵巢良性肿瘤和206例上皮性卵巢癌患者的临床病理资料,比较术前NLR和PLR在卵巢良恶性肿瘤的区别,根据统计学方法选取NLR和PLR临界值,分析NLR和PLR与上皮性卵巢癌临床病理因素的关系。通过单因素及多因素分析评估术前NLR和PLR对患者术后生存的影响。结果:术前NLR和PLR水平在上皮性卵巢癌中明显高于卵巢良性肿瘤。选取NLR=2.62和PLR=173分别作为临界值。单因素分析结果显示,FIGO分期晚、中-低分化、腹水、脉管癌栓、CA125≥35、NLR≥2.62、PLR≥173是影响患者术后无病生存期(DFS)的危险因素(P0.05);FIGO分期晚、腹水、脉管癌栓、CA125≥35、PLR≥173是影响患者术后总生存期(OS)的危险因素(P0.05)。多因素分析显示,FIGO分期晚、NLR≥2.62、脉管癌栓是上皮性卵巢癌患者DFS的独立危险因素(P0.05)。结论:NLR和PLR方便测得且价格便宜,对卵巢癌的预后有一定的评估价值。     

TTF-1和SPA表达对早期肺腺癌术后复发预测及预后的判断价值

目的 研究术后肺腺癌患者组织中TTF-1和SPA的蛋白表达对其复发的预测价值及预后的影响.方法 收集行手术切除的Ⅰ～Ⅲ期肺腺癌患者112例,采用免疫组化方法检测组织中TTF-1以及SPA的表达.结果 68例患者出现复发,TTF-1阳性和阴性表达患者中位DFS分别为41个月和9个月(P =0.013),中位OS分别为65.0和23.0个月(P=0.037),SPA阳性与阴性表达患者中位DFS分别为59.0个月和15.0个月(P=0.018),中位OS分别为68.0个月和35.0个月(P =0.058).结论 早期肺腺癌术后组织中TTF-1和SPA的表达是其复发的有效预测指标,TTF-1阳性表达预后更好.