[1083] Is Papillary Renal Cell Carcinoma Derived from Proximal Convoluted Tubules?

Ximing J Yang, Karl Dykema, Liwei Jia, Elizabeth Gersbach, Fan Lin, Steve Shen, Bin T Teh. Northwestern University Feinberg School of Medicine, Chicago, IL; Van Andel Research Institute, Grand Rapids, MI; Geisinger Health System, Danville, PA; Methodist Hospital, Houston, TX

Background: Papillary renal cell carcinoma (RCC) is hypothesized to be of proximal tubular origin. However, the supporting evidence is limited. In order to test this hypothesis, we examined the expression of a number of markers preferentially expressed in the proximal tubules and / or distal tubules of the normal kidney in papillary RCC.
Design: A total of 18 markers that are preferentially expressed in proximal (5), distal (4), both proximal and distal tubules (5), and neither (4) were studied in two groups of histologically confirmed papillary RCC by measuring their mRNA levels or protein levels. The mRNA levels were obtained from expression microarray analysis of 35 cases of papillary RCC, and gene product levels measured by immunoreactivity were evaluated in a group of papillary RCC (at least 35 cases for each marker).
Results: Three of the five proximal tubule markers and one of four distal tubule markers are expressed in papillary RCC, while three of five markers normally present in both proximal and distal tubules are positive in papillary RCC. Two of four markers normally not present in proximal or distal tubules are also positive in papillary RCC.

Table renal markers in Papillary RCC
Proximal tubule markersPRCCBoth proximal and distal tubulesPRCC
GST-aNeg (m/p)S100APos (p)
CD10Pos** (p)CA9Neg (m/p)
VillinNeg (m)CK19Neg (p)
RCCmaPos (p)Pax2Pos (p)
AMACR*Pos (m/p)Pax8Pos (p)
Distal tubule markers Neither proximal or distal tubules 
Ksp-cad*Neg (m/p)Kim1Pos (p)
CK7Pos (m/p)VimentinPos (m/p)
E-cadherinNeg (m)CK20Neg (p)
MUC1Neg (m)CkitNeg (m/p)
**Pos: at least 70% cases are positive measured by mRNA (m) and / or protein (p). *AMACR strong in proximal tubules and weak or negative in distal tubules. *Ksp-cad strong in distal tubules and weak or negative in proximal tubules.


Conclusions: Based on our results of the gene and protein expression, papillary renal cell carcinoma shows differentiation of both distal and proximal tubules. In addition, they express markers normally absent in both proximal and distal tubules of the kidney. Therefore, papillary renal cell carcinoma is most likely derived from multipotent stem cells in the kidney rather than renal proximal convoluted tubules as previously claimed.
Category: Genitourinary (including renal tumors)

Wednesday, March 6, 2013 9:30 AM

Poster Session V # 138, Wednesday Morning

 

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