S100A11 is a potential prognostic marker for clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of few cancers with rising incidence in North America. The prognosis of ccRCC is variable and difficult to predict. Stratification of patients according to disease aggressiveness can significantly improve patient management. We investigated the expression of the S100A11 protein in 385 patients with primary ccRCC using immunohistochemistry on tissue microarrays. We compared its expression with clinicopathologic parameters and patients’ survival. We also validated our results at the mRNA level on an independent set from The Cancer Genome Atlas. As a dichotomous variable (low vs. high expression), there was a significant association between S100A11 expression and tumor grade, with higher expression associated with higher tumor grades (p < 0.001). High expression was also significantly more frequently seen in higher versus lower stages (56 vs. 28 %). In the univariate analysis, high S100A11 expression was associated with significantly shorter disease-free survival (DFS) (HR = 2.28; p = 0.001). This was maintained in the multivariate analysis (HR = 1.69; p = 0.042). Expression was not associated with overall survival (OS) (p = 0.10). Comparable results were obtained when S100A11 expression was analyzed as a trichotomous variable (low, moderate, or high expression). The Kaplan–Meier survival analyses showed that higher S100A11 expression was associated with statistically significant decrease in DFS (p < 0.001), but not OS (p = 0.1).     

MicroRNA-15a tissue expression is a prognostic marker for survival in patients with clear cell renal cell carcinoma

Clinical and Experimental Medicine - None of the currently investigated molecular markers demonstrated sufficient accuracy in prognostication of the renal cell carcinoma (RCC) oncologic outcomes;...     

ADAM metallopeptidase with thrombospondin type 1 motif 16 is a potential marker for prognosis in clear cell renal cell carcinoma

The mortality rate of clear cell renal cell carcinoma (ccRCC) remains high. Immunohistochemical staining, Western blotting and real-time quantitative polymerase chain reaction were employed to evaluate ADAM (a disintegrin and metalloproteinase) metallopeptidase with thrombospondin type 1 motif 16 (ADAMTS16) levels in ccRCC tissues and paired normal tissues, and all tissues were obtained from clinical samples of 46 cases of ccRCC patients. Moreover, we analyzed the role ADAMTS16 in the progression of ccRCC using Cell Counting Kit-8 assay and flow cytometry. ADAMTS16 levels in ccRCC tissues were markedly low, relative to normal tissues, and ADAMTS16 level closely correlated with tumor stage, lymph node metastasis as well as pathological grade. Patients with elevated ADAMTS16 expressions have a more favorable survival outcome, relative to patients with low expression of ADAMTS16. In vitro study showed ADAMTS16 expression markedly decreased in ccRCC cells and acted as a tumor suppressor compared with the normal cells. The expression of ADAMTS16 is down-regulated in ccRCC tissues, relative to normal tissues, and it may inhibit the malignancies of ccRCC. Such inhibitory effect may be ascribed to the involvement of AKT/mammalian target of rapamycin signaling. Hence, the present study of ADAMTS16 will provide new insight into the underlying biological mechanisms of ccRCC.     

Lgr5 is a potential prognostic marker in patients with cervical carcinoma

Objective: To investigate the Lgr5 (Leucine-rich repeat-containing G protein-coupled receptor 5) expression in cervical carcinoma and to estimate its clinical significance. Methods: The expression of Lgr5 mRNA was evaluated by Real-time PCR in 8 pairs of surgically removed cervical cancer and adjacent normal cervical tissues. Lgr5 protein expression was evaluated by immunohistochemistry in 94 paraffin-embedded cervical carcinoma specimens. The correlation between Lgr5 expression and clinicopathological features were statistically analyzed. Results: Lgr5 expression was significantly higher in cervical cancer tissues compared with that in adjacent normal cervix. High Lgr5 expression was positively correlated with tumor size (P = 0.025) and parametrial infiltration (P = 0.027). Moreover, high levels of Lgr5 was associated with lower overall survival (P = 0.021) and recurrent-free survival (P = 0.008), especially in stage II patients (P = 0.035). Multivariate analysis showed that the expression of Lgr5 was an independent factor of recurrent-free survival for the patients with cervical carcinoma (P = 0.135). Conclusion: Lgr5 may play an important role in the development and progression of cervical carcinoma, and may be a potential therapeutic target for the treatment of cervical carcinoma.     

Histologic tumor necrosis is an independent prognostic indicator for clear cell and papillary renal cell carcinoma

Histologic tumor necrosis (TN) has been reported to indicate a poor prognosis for different human cancers. In papillary renal cell carcinoma (RCC), data regarding the prognostic impact of TN are conflicting. We retrospectively studied the pathology records of 2,333 consecutive patients who underwent nephrectomy from 1984 to 2006 at a single tertiary academic center. In multivariate analyses regarding clear cell RCC, the presence of histologic TN was an independent negative prognostic factor for metastasis-free (hazard ratio [HR], 2.32; confidence interval [CI], 1.86-2.9; P < .001) and overall (HR, 1.52; CI, 1.31-1.76; P < .001) survival. Regarding papillary RCC, the presence of histologic TN represented an independent predictor of metastasis-free (HR, 5.22; CI, 2.2-12.5; P < .001) and overall (HR, 1.69; CI, 1.11-2.58; P = .015) survival. Our findings suggest that the presence of TN is an independent predictor of clinical outcome in clear cell and papillary RCC. Thus, histologic TN might be a reliable prognostic indicator and should, therefore, routinely be examined during pathologic analysis of RCC specimens.     

The post-operative pathological prognostic parameters of clear cell renal cell carcinoma in pT1a cases

There has been a recent increase in the number of small clear cell renal cell carcinoma (ccRCC) cases, particularly in pT1a cases. The prognostic parameters for small ccRCC, however, are not well described. Herein, we assess the pathological parameters of pT1a patients. Various clinicopathological parameters were analyzed in 293 patients with pT1a ccRCC without pre-operative metastasis to predict the disease-free survival rate (DFS) and the cancer-specific survival rate (CSS). Clinicopathological parameters included age, tumor location, Fuhrman grade, lymph-vascular invasion (LVI), tumor necrosis, and growth pattern (expansive or infiltrative). In the univariate analysis, Fuhrman grade (grade 1 + 2 vs. 3 + 4), LVI, growth pattern, and tumor necrosis were parameters associated with a worse prognosis (P < 0.0001) in both the DFS and CSS. In the multivariate analysis, Fuhrman grade (P = 0.0048), growth pattern (P = 0.0275), and tumor necrosis (P = 0.0188) were statistically significant in the DFS. Fuhrman grade (P = 0.0189) and growth pattern (P = 0.0016) were also statistically significant in the CSS. Fuhrman grade, tumor necrosis, and growth pattern were independent prognostic parameters in pT1a ccRCC. Growth pattern, a previously unrecognized parameter for prognosis, can be considered a new prognostic parameter in ccRCC.     

Loss of chromosome 9p is an independent prognostic factor in patients with clear cell renal cell carcinoma.

Loss of chromosome 9p has been implicated in the progression of renal cell carcinoma. We evaluated the clinical utility of fluorescence in situ hybridization analysis of loss of chromosome 9p in 73 patients with clear cell renal cell carcinomas with varied stage, size, grade, necrosis (SSIGN) scores. Loss of chromosome 9p was observed in 13 tumors (18%). The 5-year cancer-specific survival of patients without loss of chromosome 9p was 88% and was 43% in those with loss of chromosome 9p (P<0.001). Local extension of the primary tumor according to the 2002 TNM staging system, lymph node involvement, the presence of distant metastases, and the SSIGN score were the other variables that predicted cancer-specific survival in univariate analysis. Loss of chromosome 9p was an independent prognostic factor in multivariate analysis. Our data indicate that the detection of chromosome 9p loss by fluorescence in situ hybridization analysis of clear cell renal cell carcinoma adds prognostic information beyond the pathological factors included in the current predictive models for renal cell carcinoma, such as SSIGN score.     

A comprehensive prognostic stratification for patients with metastatic renal clear cell carcinoma

PURPOSE: To develop a reliable prognostic model for patients with metastatic renal cell carcinoma (RCC) based on features readily available in common clinical settings. PATIENTS AND METHODS: A total of 197 patients with RCC who underwent nephrectomy and immunotherapy from 1995 to 2004 were retrospectively reviewed. Their mean age was 55.1+/-11.8 yrs (24-83 yrs) and mean survival time from metastasis was 22.6+/-20.2 mos (3-120 mos). The impact of 24 clinicopathological features on disease specific survival was investigated. RESULTS: On univariate analysis, constitutional symptoms, sarcomatoid differentiation, tumor necrosis, multiple primary lesions, liver metastasis, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), thrombocytosis, alkaline phosphatase, hematocrit, T stage, N stage, and nuclear grade had significant influence on survival (p<0.05). Multivariate analysis revealed the following features associated with survival: sarcomatoid differentiation [hazard ratio (HR)=2.99, p<0.001], liver metastasis (HR=2.09, p=0.002), ECOG-PS (HR=1.95, p=0.005), N stage (HR=1.94, p=0.002), and number of metastatic sites (HR=1.76, p=0.003). An individual prognostic score was defined as the sum of the weight of these features. According to prognostic scores, patients could be subdivided into 3 groups: low risk (score 0), intermediate risk (score 1 or 2), and high risk (score >or= 3). CONCLUSION: A comprehensive prognostic stratification model was developed to predict survival and stratify patients for prospective clinical trials.     

具有透明细胞乳头状肾细胞癌形态特征的透明细胞性肾细胞癌的临床病理特征

目的探讨具有透明细胞乳头状肾细胞癌形态特征的透明细胞性肾细胞癌(clear cell papillary renal cell carcinoma-like clear cell renal carcinoma, CCPRCC-like CCRCC)的临床和病理特征, 旨在提高对该类肿瘤的认识。方法回顾性分析浙江大学医学院附属第一医院诊断的3例CCPRCC-like CCRCC的临床资料、组织学形态及免疫表型, 随访患者预后并复习相关文献。结果男性2例, 女性1例, 平均年龄43岁。肿块最大径9 cm。镜下观察3例病例均包含透明细胞乳头状肾细胞癌样(CCPRCC-like)及透明细胞性肾细胞癌样(CCRCC-like)两种区域, 前者在整个瘤体所占比例为20%～90%。CCPRCC-like区域含有囊、乳头、腺管状结构。细胞核远离基底膜, 细胞核WHO/国际泌尿病理协会(ISUP)分级1级。在CCPRCC-like区域, 细胞角蛋白(CK)7表达范围10%～80%, 中等及以上强度表达。CD10表达均为100%, 主要为顶端胞膜表达。在CCRCC-like区域, 1例CK7阴性, 其余...     

Cell heterogeneity in clear cell renal cell carcinoma

The aim of this study was to define the histological spectrum, frequency and significance of nonconventional tumour cells in clear cell renal cell carcinomas (CCRCC). Fifty‐one totally sampled CCRCC were studied histologically to evaluate the spectrum of cell morphology variability, its frequency and significance, and their correlation with tumour grade and stage, and other histological parameters of aggressive behaviour like necrosis. Aside from conventional clear/eosinophilic granular cells, three additional cellular types were identified and considered in this study: small clear cells, syncytial cells and rhabdoid cells. Small clear cells were detected in 11 cases (21.5%), syncytial cells in 8 (15.6%) and rhabdoid cells in 5 (9.8%). The presence of syncytial and rhabdoid cells statistically correlated with grade (p = 0.003 and p = 0.006) and stage (p = 0.049 and p = 0.05) in CCRCC. Necrosis correlated with stage (p = 0.018) and grade (p = 0.004), but not with syncytial, rhabdoid or small clear cells. The presence of syncytial and rhabdoid cells in CCRCC is a relatively frequent event that significantly correlates with high‐grade tumours and high stage status.     

肾透明细胞癌中Eotaxin-1的表达与肿瘤增殖能力相关

目的探讨嗜酸性粒细胞趋化因子-1 Eotaxin-1在肾透明细胞癌(ccRCC)中的表达情况及其与肿瘤增殖能力的关系。方法免疫组织化学检测58例肾透明细胞癌患者肾癌组织及癌旁组织中Eotaxin-1以及增殖细胞核抗原(PCNA)的表达并分析其与肾癌临床病理特征的关系;用Western blot法分析10例相互配对肾癌组织、癌旁组织中Eotaxin-1及PCNA的表达,并对Eotaxin-1与PCNA做相关性分析。结果 Eotaxin-1主要表达于胞质,PCNA主要表达于细胞核内,Eotaxin-1和PCNA在肾癌组织的阳性率明显高于癌旁组织(P0.05);病理分级为2-3级组的Eotaxin-1及PCNA阳性率显著高于病理分级1级组(P0.01)。临床分期为Ⅲ/Ⅳ组的Eotaxin-1及PCNA阳性率显著高于临床分期Ⅰ/Ⅱ组(P0.05),有淋巴结转移组的Eotaxin-1及PCNA阳性率高于无淋巴结转移组(P0.05);10例肾癌组织中Eotaxin-1及PCNA蛋白水平显著高于癌旁组织(P0.01,P0.05);Eotaxin-1与PCNA在肾癌组织中的表达存在相关性(P0.05)。结论肾透明细胞癌组织中Eotaxin-1与肾透明细胞癌的增殖能力密切相关,对Eotaxin-1的研究可能为临床对肾透明细胞癌诊断治疗提供新的思路。     

多囊性肾透明细胞癌的病理学诊断

目的：探讨多囊性肾透明细胞癌的临床病理特点。方法：对1例多囊性肾透明细胞癌进行了免疫组化染色,并进行文献复习。结果：本例右肾肿物18年。大体见肿物由多发不等的囊腔组成。镜下囊内壁主要由单层立方或柱状上皮被覆,部分为多层并有乳头形成。瘤细胞胞质透亮,无明显异型性。癌细胞免疫表型cytokeratin、CEA和vimentin呈阳性表达。本例诊断为多囊性肾透明细胞癌。结论：多囊性肾透明细胞癌是一种罕见的肾癌病理类型。临床上主要采用根治切除术。本瘤的生物学行为属于低度恶性肿瘤。