Claudin-7 and claudin-8: immunohistochemical markers for the differential diagnosis of chromophobe renal cell carcinoma and renal oncocytoma

Osunkoya, Adeboye O.; Cohen, Cynthia; Lawson, Diane; Picken, Maria M.; Amin, Mahul B.; Young, Andrew N.

doi:10.1016/j.humpath.2008.07.002

Cited by 64 publications

(43 citation statements)

References 34 publications

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“…Bioinformatic analysis demonstrated that CLDN8 was decreased in inflammatory bowel disease (Clark et al 2012). Moreover, the expression of CLDN8 mRNA is down-regulated in tumor tissues (Gröne et al 2007), and CLDN8 has been revealed as a candidate biomarker for the diagnosis in renal cell carcinoma and renal oncocytoma (Kim et al 2009;Osunkoya et al 2009). Recent research demonstrated CLDN8 functioned as an oncogenic factor and was up-regulated in OS cells ).…”

Section: Discussionmentioning

confidence: 99%

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Yang

Hao

et al. 2017

Tohoku J. Exp. Med.

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Osteosarcoma is a malignant bone cancer that mainly affects children. SOX9 plays a key role in bone formation and osteosarcoma, and Claudin-8 (CLDN8), a tight junction protein, contributes to proliferation of osteosarcoma cells. The aim of this study was to investigate the relationship between SOX9 and CLDN8 in osteosarcoma. The expression levels of SOX9 and CLDN8 were determined in osteosarcoma specimens (n = 25) by qRT-PCR and Western blot analyses. The levels of SOX9 mRNA and protein were significantly higher in osteosarcoma tissues than those in adjacent non-tumor tissues, whereas the expression levels of CLDN8 mRNA and protein were significantly lower in osteosarcoma tissues. Immunohistochemical analysis showed the high expression of SOX9 in 56 out of 97 osteosarcoma tissues (57.7%). By contrast, the low expression of immunoreactive CLDN8 was observed in 62 of 97 osteosarcoma tissues (63.9%). There was the inverse correlation between the expression levels of SOX9 and CLDN8 proteins (R = −0.633, P < 0.001). The overall survival was poorer in the patients with high SOX9 expression. Subsequently, using two human osteosarcoma cell lines, we showed that knockdown of SOX9 inhibited cell proliferation and migration but promoted cell apoptosis. Importantly, knockdown of SOX9 increased the expression levels of CLDN8 protein. The transient luciferase-reporter assays suggest that SOX9 may inhibit the promoter activity of the CLDN8 gene in osteosarcoma cells. In conclusion, we provide the evidence demonstrating that SOX9 may promote cell growth by repressing the expression of CLDN8. Thus, SOX9 may be a therapeutic target for osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Yang

Hao

et al. 2017

Tohoku J. Exp. Med.

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“…Both of these tumor types are believed to derive from the distal nephron. 9,18,19 Previous work has identified FXYD2, the gamma subunit of the Na þ /K þ -ATPase, as a distal tubulespecific protein that is highly enriched in human kidney tissue. 17 The current study represents the first examination of FXYD2 in renal tumors.…”

Section: Discussionmentioning

confidence: 99%

“…9,18,19 In contrast, clear-cell and papillary RCCs are known to express proximal tubule markers. It is the aim of this study to explore the expression pattern of the distal tubule-specific protein, FXYD2, in RCCs and oncocytomas.…”

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confidence: 99%

Expression of the Na+/K+-transporting ATPase gamma subunit FXYD2 in renal tumors

et al. 2013

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Chromophobe renal cell carcinoma (RCC) is a form of renal cancer that may be confused with other eosinophilic renal tumors, including oncocytoma, type 2 papillary RCC, and clear-cell RCC with eosinophilic features. There are currently no robust markers to distinguish these neoplasms. Chromophobe RCC and renal oncocytoma are presumably derived from the distal nephron. FXYD2 is a distal tubule regulator of the trimeric Na þ / K þ -transporting ATPase that is enriched in kidney tissue. In this study, we investigated the expression of FXYD2 in normal human kidney, 27 chromophobe RCCs, 30 oncocytomas, 15 clear-cell RCCs, and 11 papillary RCCs. Immunohistochemical staining for FXYD2 showed diffuse, strong immunoreactivity in the basolateral membrane of distal tubules of normal human kidney. Ninety-six percent (26/27) of chromophobe RCCs were immunoreactive for FXYD2 in a distinctly membranous pattern. Twenty-five of these tumors showed at least focal 2 þ staining. In contrast, only 17% (5/30) of renal oncocytomas, 11% (2/15) of clear-cell RCCs, and 0% (0/11) of papillary RCCs displayed FXYD2 immunoreactivity. None of these cases showed Z2 þ FXYD2 staining. A subset of cases was confirmed as oncocytoma or chromophobe RCC using cytokeratin 7, colloidal iron, and interphase fluorescence in situ hybridization analysis of chromosomes 1, 2, 6, 10, and 17. Among this subset, 100% (7/7) of chromophobe RCCs were FXYD2 positive, whereas 17% (2/12) of oncocytomas were stained with FXYD2. The oncocytomas that stained with FXYD2 did so in a weak (1 þ ), patchy manner. In contrast, chromophobe RCCs showed Z2 þ staining in 86% (6/7) of these tumors. For comparison, this subset was also stained for kidney-specific cadherin (Ksp-cadherin). Ksp-cadherin showed positive staining in 100% (7/7) of chromophobe RCCs and 33% (4/12) of oncocytomas. This is the first report demonstrating the potential utility of FXYD2 immunohistochemistry in the diagnosis of chromophobe RCC.

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“…A lot has been published in relation to the diagnostic differential between the ChRCC and the RO, with multiple works that demonstrate differences between expression markers in both tumors, however most of them correspond to markers with little diffusion or infrequent use in the anatomic-pathological routine. Among them are S100-A1, Claudins 7 and 8, Endogenous Abidin binding, PAX2, RON, LMP2, Cytochrome C Oxidase and others [10][11][12][13][14][15]. However, data suggests that a set of markers is much better that a single marker, besides a rigorous revision and meticulous analysis of the morphology even architectural and cytological parameters [16,17].…”

Section: Discussionmentioning

confidence: 99%

Renal Oncocytoma and Cromophobe Renal Cell Carcinoma: Main Morphological Differences and Proposal of a Simple Histochemical and Immunohistochemical Panel to separate them

Ivan¹,

Gonzalo²,

Fern³

et al. 2014

J Clin Exp Pathol

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Claudin-7 and claudin-8: immunohistochemical markers for the differential diagnosis of chromophobe renal cell carcinoma and renal oncocytoma

Cited by 64 publications

References 34 publications

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Expression of the Na+/K+-transporting ATPase gamma subunit FXYD2 in renal tumors

Renal Oncocytoma and Cromophobe Renal Cell Carcinoma: Main Morphological Differences and Proposal of a Simple Histochemical and Immunohistochemical Panel to separate them

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