Kidney-specific cadherin correlates with the ontogenetic origin of renal cell carcinoma subtypes: an indicator of a malignant potential?

Horstmann, M.; Geiger, L. M.; Vogel, Ulrich; Schmid, Heide; Hennenlotter, Jörg; Kuehs, Ursula; Merseburger, Axel S.; Kruck, Stephan; Stenzl, Arnulf; Bedke, Jens

doi:10.1007/s00345-011-0763-3

Cited by 5 publications

(4 citation statements)

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“…The investigation of KSP-cadherin showed only a weak membranous and cytoplasmic expression in both subtypes of papillary RCC. These findings for KSP-cadherin correlate with those of other working groups [37]. P-cadherin expression which plays an important role in ovarian cancer also in case of cadherin switch [38] did not show a prominent expression in papillary RCC.…”

Section: Discussionsupporting

confidence: 86%

N-cadherin is differentially expressed in histological subtypes of papillary renal cell carcinoma

et al. 2012

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BackgroundPapillary renal cell carcinoma (RCC) represents a rare tumor, which is divided, based on histological criteria, into two subtypes. In contrast to type I papillary RCC type II papillary RCC shows a worse prognosis. So far, reliable immunohistochemical markers for the distinction of these subtypes are not available.MethodsIn the present study the expression of N(neural)-, E(epithelial)-, P(placental)-, und KSP(kidney specific)-cadherin was examined in 22 papillary RCC of histological type I and 18 papillary RCC of histological type II (n = 40).ResultsAll papillary RCC type II displayed a membranous expression for N-cadherin, whereas type I did not show any membranous positivity for N-cadherin. E-cadherin exhibited a stronger, but not significant, membranous as well as cytoplasmic expression in type II than in type I papillary RCC. A diagnostic relevant expression of P- and KSP-cadherin could not be demonstrated in both tumor entities.ConclusionThus N-cadherin represents the first immunhistochemical marker for a clear cut differentiation between papillary RCC type I and type II and could be a target for therapy and diagnostic in the future.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2011556982761733

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Section: Discussionsupporting

confidence: 86%

N-cadherin is differentially expressed in histological subtypes of papillary renal cell carcinoma

et al. 2012

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“…39,40 Clear cell and papillary RCCs, however, are less likely to stain with the marker. 13,41 A recent study has suggested that Ksp-cadherin is a sensitive marker of the t(6;11) RCC. 7 However, we found focal labeling for Ksp-cadherin in only 3 of 19 t(6;11) RCCs (Fig.…”

Section: Resultsmentioning

confidence: 99%

t(6;11) Renal Cell Carcinoma (RCC)

Smith¹,

Illei²,

Allaf³

et al. 2014

American Journal of Surgical Pathology

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Renal cell carcinomas (RCCs) harboring the t(6;11)(p21;q12) translocation were first described in 2001 and recently recognized by the 2013 International Society of Uro-logical Pathology Vancouver Classification of Renal Neoplasia. Although these RCCs are known to label for melanocytic markers HMB45 and Melan A and the cysteine protease cath-epsin K by immunohistochemistry (IHC), a comprehensive IHC profile has not been reported. We report 10 new t(6;11) RCCs, all confirmed by break-apart TFEB fluorescence in situ hybridization. A tissue microarray containing 6 of these cases and 7 other previously reported t(6;11) RCCs was constructed and immunolabeled for 21 different antigens. Additional whole sections of t(6;11) RCC were labeled with selected IHC markers. t(6;11) RCC labeled diffusely and consistently for cathepsin K and Melan A (13 of 13 cases) and almost always at least focally for HMB45 (12 of 13 cases). They labeled frequently for PAX8 (14 of 23 cases), CD117 (10 of 14 cases), and vimentin (9 of 13 cases). A majority of cases labeled at least focally for cytokeratin Cam5.2 (8 of 13 cases) and CD10 and RCC marker antigen (10 of 14 cases each). In contrast to a prior study's findings, only a minority of cases labeled for Ksp-cadherin (3 of 19 cases). The median H score (product of intensity score and percentage labeling) for phosphorylated S6, a marker of mTOR pathway activation, was 101, which is high relative to most other RCC subtypes. In summary, IHC labeling for PAX8, Cam5.2, CD10, and RCC marker antigen supports classification of the t(6;11) RCC as carcinomas despite frequent negativity for broad-spectrum cytokeratins and EMA. Labeling for PAX8 distinguishes the t(6;11) RCC from epithelioid angiomyolipoma, which otherwise shares a similar immunoprofile. CD117 labeling is more frequent in the t(6;11) RCC compared with the related Xp11 translocation RCC. Increased pS6 expression suggests a possible molecular target for the uncommon t(6;11) RCCs that metastasize.

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“…The evidence supporting a proximal tubular origin for many cases of ccRCC includes the finding that most, but not all, tumors exhibit positive immunoreactivity for various proteins that are normally expressed specifically by proximal tubular cells, including CD10, villin, renal cell carcinoma antigen, intercellular adhesion molecule 1, and multidrug resistance protein 2 (43-48). Further supporting a proximal tubular origin for ccRCC, most ccRCCs stain positively for the proximal tubule marker tetragonolobus lectin and negatively or weakly for the distal tubule markers peanut lectin (43) and Ksp-cadherin (49)(50)(51). Importantly, supervised transcriptional cluster analysis identified that ccRCCs exhibit an mRNA expression profile that is highly similar to microdissected proximal tubules but differs from the expression profiles of other microdissected nephron segments (52).…”

Section: The Cellular Origin Of Ccrccmentioning

confidence: 96%

A Clearer View of the Molecular Complexity of Clear Cell Renal Cell Carcinoma

Frew

Moch

2015

Annu. Rev. Pathol. Mech. Dis.

186

189

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The von Hippel-Lindau (VHL) tumor suppressor gene is mutated as an early event in almost all cases of clear cell renal cell carcinoma (ccRCC), the most frequent form of kidney cancer. In this review we discuss recent advances in understanding how dysregulation of the many hypoxia-inducible factor α-dependent and -independent functions of the VHL tumor suppressor protein (pVHL) can contribute to tumor initiation and progression. Recent evidence showing extensive inter- and intratumoral genetic diversity has given rise to the idea that ccRCC should actually be considered as a series of molecularly related, yet distinct, diseases defined by the pattern of combinatorial genetic alterations present within the cells of the tumor. We highlight the range of genetic and epigenetic alterations that recur in ccRCC and discuss the mechanisms through which these events appear to function cooperatively with a loss of pVHL function in tumorigenesis.

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Kidney-specific cadherin correlates with the ontogenetic origin of renal cell carcinoma subtypes: an indicator of a malignant potential?

Abstract: In this cohort, the origin of tumour subtypes-chRCC and oncocytomas develop from DT and ccRCC and pRCC from PT cells-is mirrored by the respective Ksp-cad expression. This raises the question whether DT-derived tumours have a less malignant potential than PT-derived tumours.

Cited by 5 publications

References 24 publications

N-cadherin is differentially expressed in histological subtypes of papillary renal cell carcinoma

N-cadherin is differentially expressed in histological subtypes of papillary renal cell carcinoma

t(6;11) Renal Cell Carcinoma (RCC)

A Clearer View of the Molecular Complexity of Clear Cell Renal Cell Carcinoma

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