scholarly journals Morphological and Molecular Study of Hybrid Oncocytic/Chromophobe Tumor of the Kidney Associated with Sporadic Renal Oncocytosis and Chronic B-Cell Lymphocytic Leukemia: The Possible Contribution of Lymphoma to Renal Oncocytosis

Pathobiology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Miguel A. Idoate ◽  
Inmaculada Trigo ◽  
Jesús Saenz de Zaitigui ◽  
Manuel Pérez-Pérez ◽  
Juan José Ríos

Hybrid oncocytic/chromophobe tumor (HOCT) of the kidney arising from a precursor oncocytosis not associated with the Birt-Hogg-Dubé (BHD) syndrome is an unusual and highly interesting neoplasm. Immunohistochemical and molecular findings suggest that HOCT is an entity distinct from both oncocytoma and chromophobe carcinoma. Although uncertainty persists regarding the factors predisposing to the development of HOCT, experimental findings suggest that it may arise due to the effect of toxins or in association with chronic kidney failure. The potential role of prior renal lymphoma in the development of oncocytosis has not hitherto been examined. We present a morphological, immunohistochemical, and molecular analysis of an HOCT arising from renal oncocytosis in conjunction with CLL affecting the kidney. The findings suggest that this tumor belongs to a family of similar neoplasms including oncocytoma, the eosinophilic variant of chromophobe renal-cell carcinoma (CRCC), and low-grade oncocytic tumor, even though these neoplasms may arise from different precursor lesions. HOCT and oncocytosis revealed the same immunohistochemical profile consistent on positivity for epithelial membrane antigen (EMA), cytokeratin 7 (Ck7), E-cadherin, CAM 5.2 and negativity for Pax-8, vimentin, renal-cell carcinoma (RCC) antigen, CD117, racemase, progesterone receptor, and CD10. The Ki-67 proliferation index was <1%. Molecular analysis of the tumor revealed the AKT3 gene mutation variant, classified as probably pathogenic, together with FOS1 gene amplification and no copy number variations (CNVs). Finally, we present a case of HOCT arising from a nonhereditary renal oncocytosis in conjunction with B lymphoma that raises interesting questions regarding pathogenesis.

2021 ◽  
Vol 22 (15) ◽  
pp. 7913
Author(s):  
Julia Oto ◽  
Raquel Herranz ◽  
Emma Plana ◽  
José Vicente Sánchez-González ◽  
Javier Pérez-Ardavín ◽  
...  

Renal cell carcinoma (RCC) is the third most frequent urinary malignancy and one of the most lethal. Current diagnostic and follow-up techniques are harmful and unspecific in low-grade tumors. Novel minimally invasive markers such as urine microRNAs (miRNAs) are under study. However, discrepancies arise among studies in part due to lack of consent regarding normalization. We aimed to identify the best miRNA normalizer for RCC studies performed in urine samples together with a miRNA profile with diagnostic value and another for follow-up. We evaluated the performance of 120 candidate miRNAs in the urine of 16 RCC patients and 16 healthy controls by RT-qPCR followed by a stability analysis with RefFinder. In this screening stage, miR-20a-5p arose as the most stably expressed miRNA in RCC and controls, with a good expression level. Its stability was validated in an independent cohort of 51 RCC patients and 32 controls. Using miR-20a-5p as normalizer, we adjusted and validated a diagnostic model for RCC with three miRNAs (miR-200a-3p, miR-34a-5p and miR-365a-3p) (AUC = 0.65; Confidence Interval 95% [0.51, 0.79], p = 0.043). let-7d-5p and miR-205-5p were also upregulated in patients compared to controls. Comparing RCC samples before surgery and fourteen weeks after, we identified let-7d-5p, miR-152-3p, miR-30c-5p, miR-362-3p and miR-30e-3p as potential follow-up profile for RCC. We identified validated targets of most miRNAs in the renal cell carcinoma pathway. This is the first study that identifies a robust normalizer for urine RCC miRNA studies, miR-20a-5p, which may allow the comparison of future studies among laboratories. Once confirmed in a larger independent cohort, the miRNAs profiles identified may improve the non-invasive diagnosis and follow-up of RCC.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2574
Author(s):  
Jee Soo Park ◽  
Myung Eun Lee ◽  
Won Sik Jang ◽  
Koon Ho Rha ◽  
Seung Hwan Lee ◽  
...  

Genes associated with the DEAD-box helicase DDX11 are significant biomarkers of aggressive renal cell carcinoma (RCC), but their molecular function is poorly understood. We analyzed the molecular pathways through which DDX11 is involved in RCC cell survival and poly (ADP-ribose) polymerase (PARP) inhibitor sensitivity. Immunohistochemistry and immunoblotting determined DDX11 expression in normal kidney tissues, benign renal tumors, and RCC tissues and cell lines. Quantitative polymerase chain reaction validated the downregulation of DDX11 in response to transfection with DDX11-specific small interfering RNA. Proliferation analysis and apoptosis assays were performed to determine the impact of DDX11 knockdown on RCC cells, and the relevant effects of sunitinib, olaparib, and sunitinib plus olaparib were evaluated. DDX11 was upregulated in high-grade, advanced RCC compared to low-grade, localized RCC, and DDX11 was not expressed in normal kidney tissues or benign renal tumors. DDX11 knockdown resulted in the inhibition of RCC cell proliferation, segregation defects, and rapid apoptosis. DDX11-deficient RCC cells exhibited significantly increased sensitivity to olaparib compared to sunitinib alone or sunitinib plus olaparib combination treatments. Moreover, DDX11 could determine PARP inhibitor sensitivity in RCC. DDX11 could serve as a novel therapeutic biomarker for RCC patients who are refractory to conventional targeted therapies and immunotherapies.


2001 ◽  
Vol 51 (12) ◽  
pp. 954-960 ◽  
Author(s):  
Masako Otani ◽  
Tohru Shimizu ◽  
Hiromi Serizawa ◽  
Yoshiro Ebihara ◽  
Yoji Nagashima

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Ameer Hamza ◽  
Deepika Sirohi ◽  
Steven C. Smith ◽  
Mahul B. Amin

Author(s):  
Ayan Kundu ◽  
Anway Sen ◽  
Shouvik Choudhury ◽  
Tapan Kumar Mandal ◽  
Debasish Guha ◽  
...  

Background and aims. Renal cell carcinoma (RCC) seems to be the most aggressive type of genitourinary neoplasm. Down regulation of normal beta-catenin expression contributes to development of RCC, reflecting the role of beta-catenin/Wnt signaling pathway in pathogenesis. This study aims to evaluate the significance of beta-catenin expression and its correlation with the prognostic parameters. Methods. A cross-sectional observational study was carried out in a tertiary care center on 58 RCC cases using variables like histological grade and type, tumor stage, necrosis. Formalin fixed, paraffin-embedded blocks were evaluated for beta-catenin expression by immunohistochemistry using scoring system. Data were analyzed by mean ± SD, χ2 test, Pearson’s correlation test. Results. Membranous score (MS) had a strong negative correlation with tumor stage (r = -0.407, p = 0.044) and grade (r = -0.787, p = <0.001). Mean membranous score difference between low (Stage 1 and 2) vs. high stage (Stage 3 and 4) and low (Grade 1 and 2) vs. high grade (Grade 3 and 4) was statistically significant (p < 0.001). Cytoplasmic score (CS) had positive correlation with tumor stage (r = 0.586; p = 0.002). No significant correlation was evident between cytoplasmic scores and tumor grade, however the mean cytoplasmic score difference between low grade vs. high grade was statistically significant (p < 0.001). Conclusion. Beta-catenin may play a crucial role in the pathogenesis of RCC and has a positive correlation with the biological behavior of this tumor. The important role of beta-catenin as a prognostic parameter and probably a critical evaluator of targeted chemotherapy cannot be overemphasized.


2020 ◽  
Vol 2020 (2) ◽  
Author(s):  
Koujin Miura ◽  
Yasushi Adachi ◽  
Toshiaki Shirahase ◽  
Yoji Nagashima ◽  
Kazuki Suemune ◽  
...  

Abstract Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal cell carcinoma that initially presents as low-grade renal cell carcinoma. However, cases of MTSCC with high-grade histology and poor prognosis have been reported. Here, we report a case of MTSCC with high-grade histological features and metastasis. A 77-year-old woman consulted a hospital following frequent and painful micturition. Computed tomography scan revealed a tumor of the left kidney. First, chemotherapy was performed, with no effects. Therefore, nephrectomy was subsequently performed. Histologically, the tumor showed the features of MTSCC with sarcomatoid component. Metastasis of the tumor into the lymph node was also observed. Although adjuvant chemotherapy was performed after nephrectomy, metastasis to the lungs and bone and local recurrence was observed. The patient is still alive 2 years after nephrectomy with metastasis and recurrence of the tumor. High-grade MTSCC shows a relatively poor prognosis, specifically MTSCC with metastasis upon nephrectomy.


2004 ◽  
Vol 46 (1) ◽  
pp. 118-125 ◽  
Author(s):  
I Kausch ◽  
H Jiang ◽  
C Brocks ◽  
K Bruderek ◽  
S Krüger ◽  
...  

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