Immunohistochemical Analysis for Cytokeratin 7, KIT, and PAX2 Value in the Differential Diagnosis of Chromophobe Cell Carcinoma

Department of Pathology Unit, Mediterranean Institute of Oncology, Catania, Italy.
American Journal of Clinical Pathology (Impact Factor: 2.51). 03/2007; 127(2):225-9. DOI: 10.1309/9KWEA4W9Y94D1AEE
Source: PubMed


Immunohistochemical staining for cytokeratin 7 (CK7), KIT, and PAX2 expression was performed on 91 renal neoplasms, 37 conventional (clear cell) renal cell carcinomas (CRCCs), 20 papillary RCCs (PRCCs), 11 chromophobe RCCs (ChCs), and 23 oncocytomas, with available karyotypes. All ChCs, 19 PRCCs, 2 CRCCs, and 1 oncocytoma were CK7+; all ChCs, 22 oncocytomas, 2 CRCCs, and no PRCCs expressed KIT; PAX2 was positive in 31 CRCCs, 17 PRCCs, 20 oncocytomas, and 1 ChC. The predominant expression profiles were as follows: CRCC, CK7-/KIT-/PAX2+ (26/37); PRCC, CK7+/KIT-/PAX2+ (17/20); ChC, CK7+/KIT+/PAX2- (10/11); and oncocytoma, CK7-/KIT+/PAX2+ (19/23). Cytogenetic analysis showed that the sole PAX2+ ChC had a retained chromosome 10, and all ChCs with chromosome 10 loss were PAX2-. These results identify specific staining patterns of the 4 major histologic subtypes of renal neoplasms and raise the question of a relationship between chromosome 10 loss and loss of PAX2 expression in ChC.

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Available from: Vundavalli V Murty
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    • "Fernandez-Acenero et al.3 also explored a wide immunohistochemical panel for the differential diagnosis of renal tumors with oncocytic features, including cytokeratins 7 and 20, CD117, CD10, p53, progesterone and racemase and found no specific, single marker for the accurate diagnosis of these tumors.3 Other explored immunohistochemical markers include kidney-specific cadherin, cytokeratin 7, KIT and PAX 2, claudin-7 and 8, MAGE-A3/4, NY-ESO-1, caveolin1, CD63 and cytokeratin 14.4-8,11,12 TGF-β1 is a cytokine involved in regulating a number of cellular processes including proliferation, differentiation, apoptosis, development, tissue repair, cell motility, extracellular matrix formation, inflammation, immunosuppression, and tumorigenesis.13 TGF-β1 induces differentiation of fibroblasts to myofibroblasts in a number of physiologic and pathologic processes.17-19 "
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    ABSTRACT: Distinguishing renal oncocytoma (RO) from the eosinophilic variant of chromophobe renal cell carcinoma (ChRCC) under the light microscope is a common diagnostic problem. Our recent research has shown significant difference between the presence of tumor fibrous capsule in ChRCCs and ROs. Transforming growth factor beta 1 (TGF-β1) is a potent cytokine involved in regulating a number of cellular processes. Two main purposes of this research were to investigate whether the TGF-β1 staining could be related to the presence of tumor fibrous capsule and if it could be used in the differential diagnosis between ChRCC and RO. We investigated 34 cases: 16 ChRCCs (8 eosinophilic and 8 classic) and 18 ROs. All available slides of each tumor, routinely stained with hematoxylin and eosin (H&E) were first analyzed to note the presence of tumor fibrous capsule. One paraffin embedded tissue block matching the representative H&E slide was selected for the immunohistochemical analysis. TGF-β1 expression was analyzed semiquantitatively in the tumor tissue, the tumor fibrous capsule, if present and the peritumoral renal parenchyma. Intensity of TGF-β1 expression was weaker in ChRCCs than the one observed in ROs (P<0.05). The type of reaction in ChRCCs was predominantly membranous unlike in ROs, which exhibited a predominantly cytoplasmic reaction (P<0.05). Moreover, none of the ROs showed membranous type of reaction for TGF-β1. In the group of ChRCCs, tumors with capsule had statistically significant higher quantity of TGF-β1 expression in tumor tissue and in peritumoral renal parenchyma compared to the tumors without capsule (P<0.05). Our results showed different types of TGF-β1 expression in ChRCCs and ROs: ChRCCs had predominantly membranous type of reaction, and ROs predominantly cytoplasmic. Furthermore, ChRCCs with capsule had statistically significant higher quantity of TGF-β1 expression in tumor tissue and in peritumoral renal parenchyma compared to the tumors without capsule. Based on these findings we can speculate that it could be possible that TGF-β1 plays a role in the formation of fibrous capsule in ChRCCs.
    Full-text · Article · Jan 2014 · European journal of histochemistry: EJH
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    • "IIt is interesting to note that several patients who experienced progression on one anti-VEGF therapy and who were subsequently switched to another anti-VEGF therapy achieved substantial response. Although the overall duration of follow-up was relatively short, the results support the clinical rationale for continued targeting of the VEGF and c-Kit signaling pathways in non-clear cell RCC [9,10]. A phase III trial of temsirolimus also included patients with non-clear cell histology, and a subgroup analysis demonstrated an improved overall survival on temsirolimus in comparison with interferon and the combination of both drugs [11]. "
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    ABSTRACT: Chromophobe renal cell carcinoma is universally accepted as a distinct subtype of renal cell carcinoma. There are conflicting reports on prognosis, and few data on response to treatment exist. Currently, we do not have any effective treatment for the metastatic disease apart from surgical procedures. Current strategies are based on results obtained in the context of clear cell-type renal cell carcinoma. Separate trials for rare histologies seem unfeasible and are unlikely to be performed. For these cases, clinical observations are an important part for advancing therapeutic insight. In recent years, novel tyrosine kinase inhibitors have been shown to have significant clinical benefit in advanced renal cell carcinoma. We present the case of a 43-year-old Caucasian man with advanced chromophobe renal cell carcinoma treated with the tyrosine kinase inhibitor sunitinib and subsequently with sorafenib and the mammalian target of the rapamycin inhibitor everolimus, achieving a prolonged response and significant clinical benefit. We report an unexpectedly high efficacy of everolimus as a third-line treatment in a patient with metastatic chromophobe renal cell carcinoma. Up to now, no published data from randomized clinical studies have addressed the question of efficacy of everolimus as a third-line treatment after failure of tyrosine kinase inhibitors. To the best of our knowledge, this case is the first report of chromophobe renal cell carcinoma treated successfully with sequential tyrosine kinase and mammalian target of rapamycin inhibitor therapy. Notably, the time on treatment with sunitinib exceeded four years. The case presented here implies that everolimus could be a viable option for patients with metastatic chromophobe renal cell carcinoma.
    Full-text · Article · Apr 2012 · Journal of Medical Case Reports
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