Dynamic changes of different phenotypic and genetic circulating tumor cells as a biomarker for evaluating the prognosis of RCC

Background: Circulating tumor cells (CTCs) and relevant autophagy Beclin-1 genes expression are critical biomarkers for tumorigenesis and tumor progress. Here we investigated the relationship of dynamic changes of CTCs and Beclin-1 expression of CTCs with renal cell carcinoma (RCC) prognosis.

Materials and methods: A total of 69 patients with RCC were enrolled and divided into two groups based on the postoperative status of distant metastasis, including metastasis-free group (n = 58) and metastatic group (n = 11). Demographic characteristics of each patient were recorded in detail. All 69 enrolled patients had received multiple CTC tests and peripheral blood samples were obtained at three different time points (1 day before operation, 6 months and 12 months after operation). Peripheral blood samples were drawn before each time point and CTCs were separated by using Can Patrol CTC enrichment technique. CTCs were divided into epithelial, mesenchymal and mixed phenotype based on different surface biomarkers. RNA in situ hybridization assay was used to detect the expression of Beclin1 gene.

Results: The percentages of epithelial, mesenchymal and mixed CTCs were 11.64%, 28.04% and 60.32%, respectively. There were no significant differences of initial CTCs counts between metastasis-free group (8.43 ± 5.15) and metastatic group (7.71 ± 3.82) (P > 0.05). As for metastatic group, the number of mixed CTCs at 12 months postoperatively was significantly higher than that of mixed CTCs preoperatively and 6 months postoperatively (P < 0.05). In the metastatic group, the number of Beclin1 positive CTCs was significantly higher than that of Beclin1 negative CTCs preoperatively (P < 0.05), moreover, there were several significantly changes of Beclin1 positive CTCs with different types and at different time points.

Conclusion: The recurrence or metastasis of RCC was uncorrelated with initial CTCs counts, but probably related with the variation trend of CTCs, especially mesenchymal CTCs and Beclin1 positive CTCs.     

维持性血液透析并发肾癌的临床病理特点

目的:探讨维持性血液透析并发肾癌的临床病理特点及预后。方法:回顾性分析我院2013年01月至2020年01月收治的10例维持性血液透析并发肾癌患者的临床病理资料,并与同期肾功能正常肾癌患者比较。结果:男6例,女4例;平均年龄49.4(31～63)岁,维持血透时间平均49.6（19～62）个月。3例患者存在获得性肾囊肿。临床表现为肉眼血尿1例,其余9例无肾肿瘤临床症状。肿瘤均单侧单发。肿瘤最大径平均为3.9（1.2～5.4） cm。仅1例血尿患者临床分期T3aN0M0,余9例临床分期T1N0M0。患者均行后腹腔镜根治性肾切除术。术后病理证实为肾透明细胞癌9例（90%）,乳头状肾细胞癌1例（10%）。相较肾功能正常肾癌患者,维持性血液透析并发肾癌患者具有年轻、瘤体小和分级低的特点（P＜0.05）,且平均随访64.7（26～104）个月,患者均存活,未见肿瘤复发及远处转移。结论:维持性血液透析并发肾癌患者具有较好的临床病理结果,积极手术治疗预后好。维持性血液透析患者需警惕并发肾癌的风险,由于患者大多无临床症状,故需定期筛查。     

Assessment of prognosis by established prognosis scores and physicians’ judgement in mRCC patients: an analysis of the STAR-TOR registry

BackgroundTemsirolimus is a mTOR inhibitor approved for the first-line treatment of advanced or metastatic renal cell carcinoma (a/mRCC) with poor prognosis. In treatment of a/mRCC several prognostic scoring systems are used. We assessed the prognostic value of these scores in a large temsirolimus treated cohort and compared the results with the physician’s prognosis.MethodsA German multicenter registry (STAR-TOR) for a/mRCC patients ({"type":"clinical-trial","attrs":{"text":"NCT00700258","term_id":"NCT00700258"}}NCT00700258) was established to evaluate the efficacy and safety of temsirolimus 25 mg weekly in a routine clinical setting. These prospective data were systematically analyzed and followed-up by an independent clinical research organization to compare established prognostic scores (MSKCC, IMDC and Hudes) with the risk assessment by treating physicians based on their medical expertise and match them with survival outcomes.ResultsThis interim analysis included 547 patients between 02/2008 and 05/2015 in 87 centers. Either prognostic tool resulted in significant and clinically meaningful differentiation between good, intermediate and poor prognosis. However, physician’s prognosis identified more patients with good prognosis (9.1% vs. 1.3%). In patients with good physician’s prognosis and intermediate prognosis by MSKCC, overall survival was nearly doubled compared to consensual intermediate prognosis (26.6 vs. 13.6 months), albeit without reaching statistical significance (P=0.09). For poor prognosis assessed by the physician, MSKCC performed statistically better for differentiation between poor and intermediate prognosis with a median overall survival of 10.3 vs. 5.5 months (P<0.01).ConclusionsPhysician’s prognosis may be able to identify a subset of patients treated with temsirolimus with good prognosis when MSKCC-determines intermediate prognosis while the MSKCC score could identify patients which were falsely placed in the poor risk group by physicians.     

肾细胞癌靶向治疗的临床研究进展

肾细胞癌（RCC ）是难治的恶性肿瘤之一,对放化疗不敏感,免疫治疗方式有效率一直徘徊于10% ～15% 。随着对肿瘤分子机制的深入以及多种分子靶向药物的深入研究,靶向治疗取得了重大进展。肾癌的发病机制与VHL 、Ras、PTEN等抑癌基因的突变有关,可诱导其下游的蛋白激酶受体表达异常。而蛋白激酶抑制剂可以通过干扰细胞内信号传导通路及改变肿瘤细胞微环境而影响肿瘤细胞的存活和增殖,是当前研发最集中的靶向治疗药物之一。近年来,多项靶向药物临床试验的可喜结果为转移性肾细胞癌（mRCC）治疗带来了新希望。本文就2009年NCCN 肿瘤治疗指南中介绍的舒尼替尼、索拉非尼、Temsirolimus、贝伐单抗等四种药物在肾细胞癌靶向治疗方面的临床研究最新进展展开综述。     

透明细胞肾细胞癌中cIAP1、cIAP2、XIAP的表达及其与临床指标的关系

目的：检测肾透明细胞癌中凋亡抑制蛋白cIAP1、cIAP2和xIAP基因表达状况及其与,临床病理指标间的关系。方法：采用RT-PCR方法检测cIAP1、cIAP2和XIAP在透明细胞肾细胞癌中RNA水平的表达。分析其与透明细胞肾细胞癌,临床病理指标间的关系。结果：在透明细胞‘肾细胞癌中cIAP1和cIAP2的mRNA阳性率分别为85％（17／20）和60％（12／20）,均高于正常肾组织。cIAP1 mRNA在Fuhrman核分级1、2级的肾细胞癌中表达高于核分级3和4的肿瘤。XIAP的表达在肾细胞癌与癌旁正常肾组织间无差异,并与TNM分期、Fuhrman分级没有相关性。结论：IAP家族成员cIAP1与肾细胞癌的临床病理指标相关。     

A morphology-based nephrometry score to predict pathological upstaging to T3 renal cell carcinoma

BackgroundPatients with clinical T1-2 renal cell carcinoma (RCC) upstaging to pathological T3 showed worse survival prognosis than those without upstaging. We aimed to develop and validate a morphology-based nephrometry scoring system for predicting pathological upstaging to T3 of RCC.MethodsWe retrospectively reviewed 200 patients with clinical T1-2 RCC who underwent surgical treatment. The nephrometry scores were measured through preoperative computed tomography images. The risk factors of pathological upstaging were identified by logistic regression models. The predictive accuracy of a novel morphology-based nephrometry scoring system (M-Index), was compared with R.E.N.A.L (radius, exophytic/endophytic, nearness, anterior/posterior, location), PADUA (preoperative aspects and dimensions used for an anatomic classification), DAP (diameter, axial, polar) and C-Index scores.ResultsThe upstaging rate of the population was 17% (34 out of 200 patients). The upstaging and non-upstaging groups were comparable in terms of age, gender ratio, body mass index, tumor laterality, and pathological type, while the upstaging group tended to have large tumor diameter, irregular tumor morphology, inner tumor location, and short polar and axial distance. Large tumor diameter refers to larger than 5 cm, while irregular tumor morphology refers to not regular shapes such as round, oval, or lobular. Univariate and multivariate logistic regression analyses showed that tumor morphology [odds ratio (OR) 3.26, 95% confidence interval (CI): 1.79–5.97] and tumor rim location (OR 2.95, 95% CI: 1.16–7.46) were independent risk factors for pathological upstaging. The receiver operating characteristic curve and decision curve analysis (DCA) demonstrated the novel M-Index based on tumor morphology and rim location outperformed R.E.N.A.L, PADUA, DAP, and C-Index in the prediction of pathological upstaging (area under curve 0.756 vs. 0.728 vs. 0.641 vs. 0.661 vs. 0.743).ConclusionsConsisting of fewer non-complex parameters, the M-Index is an intuitive and practical tool with satisfactory predictive power for pathological upstaging to T3 in RCC patients undergoing surgery.     

Exposed proliferation antigen 210 (XPA-210) in renal cell carcinoma (RCC) and oncocytoma: clinical utility and biological implications

What's known on the subject? and What does the study add? The exposed proliferation antigen 210 (XPA‐210) of the proliferation marker thymidine kinase 1 (TK1) showed higher expression levels in metastatic renal cell carcinoma. The current study used a new XPA‐210 antibody to clarify the role of TK1 tissue expression in the largest reported cohort of different renal cell carcinoma types and oncocytomas.

OBJECTIVE

• ? To determine the clinical role of the exposed proliferation antigen 210 (XPA‐210) of the proliferation marker thymidine kinase 1 (TK1) in a large cohort of different renal cell carcinoma (RCC) types, oncocytomas and normal renal tissues samples, as TK1 is reported to be of clinical significance in several cancer entities and is suggested as a prognostic serum biomarker for RCC.

PATIENTS AND METHODS

• ? Expressions of XPA‐210 were determined immunohistochemically in 40 clear cell RCCs (ccRCC), 25 papillary RCCs (papRCC), 17 chromophobe RCC (chRCC), 27 oncocytomas and 64 normal renal parenchyma paraffin‐embedded specimens.
• ? Immunohistochemistry was performed with a monoclonal anti‐XPA‐210 antibody. Staining was measured by the percentage of positive cells.
• ? Expression was compared between subgroups and correlated with respective clinical data using one‐way analysis of variance with post hoc Tukey‐Kramer analyses.

RESULTS

• ? XPA‐210 staining in the RCC subgroup was significantly different from the oncocytomas (mean [sem ] 4.1 [0.4] vs 2.2 [0.4]; P = 0.004) and from normal renal tissue (1.0 [0.1]; P < 0.001], whereas oncocytomas did not differ from normal renal parenchyma staining (P = 0.18).
• ? Subdivided into RCC groups, only ccRCC (mean [sem ] 5.1 [0.6]; P < 0.001) and papRCC (4.4 [0.6]; P < 0.001) varied from normal renal parenchyma, whereas chRCC (1.4 [0.3]; P = 0.99) did not.
• ? RCC XPA‐210 staining was significantly associated with higher tumour stage (T = 3, P = 0.002) and grade (G = 3, P = 0.001).

CONCLUSIONS

• ? The malignant character of RCC is reflected by higher XPA‐210 expression as compared with oncocytomas and normal kidney.
• ? The ccRCC and papRCC subgroups had higher XPA‐210 levels.
• ? XPA‐210 could be considered a potential marker for the assessment of the proliferative activity in primary RCC.

     

Detecting circulating tumor DNA in renal cancer: An open challenge

Background

Detection of circulating tumor DNA (ctDNA) in blood of cancer patients is regarded as an important step towards personalized medicine and treatment monitoring. In the present study, we investigated the clinical applicability of ctDNA as liquid biopsy in renal cancer.