Adult renal cell carcinoma (RCC) with rhabdoid features is a recently recognized morphologic variant of kidney carcinoma. To date, only very few studies have been published on this subject and p53 was not previously studied.
To evaluate clinical attributes, morphology, and immunohistochemistry in RCC with rhabdoid component.
Reviewing a consecutive series of 310 RCCs, we identified 14 cases of RCC with rhabdoid features. All cases were reviewed and subjected to detailed clinical and pathologic studies with immunohistochemical evaluation of p53.
All tumors were clear RCCs with rhabdoid component representing from 5% to 50% of the tumor volume. Rhabdoid cells were large with a central eosinophilic intracytoplasmic inclusion and an eccentric atypical nucleus. Tumor necrosis was common (13/14) and sometimes extensive. Nine of 14 tumors were staged pT3, 4 of 14 were pT2, and only 1 tumor was pT1. On immunohistochemistry, rhabdoid cells were positive for vimentin (14/ 14), epithelial membrane antigen (11/14), and cytokeratin (9/14). Desmin and smooth muscle actin were always negative. p53 was positive in 10 of 14 tumors in the rhabdoid areas (5%-50% of tumor cells stained) but only in 5 of 14 cases in usual clear renal cell areas. In the follow-up, 10 of 14 patients developed metastases and 6 of 14 died of the disease. The median of survival was 8 months.
We showed that RCC with rhabdoid features is a very aggressive neoplasm with a poor prognosis. We observed an overexpression of p53 in the rhabdoid component that may be implicated in the tumor dedifferentiation.
"One study suggests that RCC with rhabdoid features is a highly aggressive neoplasm with a malignant behavior that may be due to the high activity of cell proliferation of the rhabdoid area.13 Another study suggests that rhabdoid areas show higher immunohistochemical p53 positivity than non-rhabdoid areas in the same tumors.15 Molecular genetic studies in a few cases have shown concordant loss of chromosome 3p and a VHL gene mutation in rhabdoid and clear cells from the same case, suggesting divergent differentiation from the same clone.22 "
[Show abstract][Hide abstract] ABSTRACT: Due to advancements in treatment of metastatic and advanced renal cell carcinoma (RCC), it has become increasingly important to diagnose metastatic RCC and the specific subtype. In this study, we investigated the diverse histologic features of metastatic clear cell renal cell carcinoma (CCRCC) cases in comparison with corresponding primary lesions.
We identified 119 metastatic CCRCC cases from 81 corresponding primary lesions diagnosed between 1995 and 2010 and evaluated the diverse histologic and immunohistochemical features of these lesions.
A total of 44 primary lesions (54.3%) had a non-clear cell component in addition to a typical clear cell component. Of the 119 metastatic lesions, 63 lesions (52.9%) contained a non-clear cell component, and 29 metastatic lesions were composed of a non-clear cell component only. Rhabdoid features were the most frequent non-clear cell histology among the metastatic lesions. Metastatic CCRCCs mainly showed positive CD10 and epithelial membrane antigen staining and negative cytokeratin 7 staining.
Metastatic CCRCC commonly showed a variety of histologic features. If there is a difficulty to diagnose metastatic CCRCC due to a variety of histologic features or small biopsy specimen, histologic review of the primary lesion and immunohistochemical analysis can help determine the correct diagnosis.
The Korean Journal of Pathology 10/2013; 47(5):426-432. DOI:10.4132/KoreanJPathol.2013.47.5.426 · 0.17 Impact Factor
"Renal cell carcinoma (RCC) is the third most common urological cancer after prostate and bladder cancer, but it has the highest mortality rate, at over 40%. RCC of the clear cell type is the most common malignant tumor of the kidney and has a poor prognosis.1,2 Approximately one-third of patients with RCC develop metastasis, and systemic treatment, such as chemotherapy and cytokines, has not proven to be effective. "
[Show abstract][Hide abstract] ABSTRACT: BACKGROUNDOBJECTIVE: MicroRNAs (miRNAs) are small noncoding RNAs (ribonucleic acids), approximately 22 nucleotides in length, that function as regulators of gene expression. Dysregulation of miRNAs has been associated with the initiation and progression of oncogenesis in humans. The cell division cycle (CDC)25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation.
Using miRNA target prediction software, we found that miR-141 could target the 3' untranslated region (3'UTR) sequence of CDC25B. To shed light on the role of miR-141 in renal cell carcinogenesis, the expression of miR-141 was examined by real-time polymerase chain reaction (RT-PCR) in renal cell carcinoma and normal tissues. The impact of miR-141 re-expression on 769-P cells was analyzed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony-forming assay. A luciferase reporter assay was applied to prove the functionality of the miR-141 binding site.
miR-141 is significantly downregulated in renal cell carcinoma. miR-141 re-expression suppressed cell growth in 769-P cells. Luciferase expression from a reporter vector containing the CDC25B-3'UTR was decreased when this construct was transfected with miR-141 in 769-P cells. The overexpression of miR-141 suppressed the endogenous CDC25B protein level in 769-P cells.
For the first time, we demonstrated that CDC25B is a direct target of miR-141 in renal cell carcinoma. The transcriptional loss of miR-141 and the resultant increase in CDC25B expression facilitates increased genomic instability at an early stage of renal cell carcinoma development.
OncoTargets and Therapy 04/2013; 6:349-54. DOI:10.2147/OTT.S41343 · 2.31 Impact Factor
"Renal cell carcinoma of the clear cell types is the most common malignant tumor of the kidney, which has a poor prognosis (Leroy et al., 2007;Young et al., 2008). Approximately one-third of patients with renal cell carcinoma develop metastasis, and systemic treatment such as chemotherapy and cytokines has not proved to be effective. "
[Show abstract][Hide abstract] ABSTRACT: Cdc25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of Cdc25B in renal cell carcinomas remains unknown. To shed light on influence on renal cell carcinogenesis and subsequent progression, Cdc25B expression was examined by real-time RT-PCR and western blotting in renal cell carcinoma and normal tissues. 65 kDa Cdc25B expression was higher in carcinomas than in the adjacent normal tissues (P<0.05), positive correlations being noted with clinical stage and histopathologic grade (P<0.05). To additionally investigate the role of Cdc25B alteration in the development of renal cell carcinoma, Cdc25B siRNA was used to knockdown the expression of Cdc25B. Down-regulation resulted in slower growth, more G2/M cells, weaker capacity for migration and invasion, and induction of apoptosis in 769-P transfectants. Reduction of 14-3-3 protein expression appeared related to Cdc25B knockdown. These findings suggest an important role of Cdc25B in renal cell carcinoma development and provide a rationale for investigation of Cdc2B-based gene therapy.
Asian Pacific journal of cancer prevention: APJCP 03/2012; 13(3):931-5. DOI:10.7314/APJCP.2012.13.3.931 · 2.51 Impact Factor
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