CK7 and Claudin 7 Are Superior to Other Markers in Distinguishing Oncocytoma from Chromophobe Renal Cell Carcinoma – Automatic Imaging Analysis and Hierarchical Clustering Analysis
LJ Eisengart, SM Rohan, V Parimi, JJ Wei, XJ Yang. Northwestern University, Chicago, IL
Background: Distinguishing oncocytoma (ONC) from chromophobe renal cell carcinoma (CHR) can be a diagnostic challenge. The utility of immunohistochemical (IHC) stains in differentiating these tumor subtypes has been an active area of investigation. However, to date, a specific marker or panel of markers that would be useful in this regard has remained elusive. We assessed the diagnostic utility of a panel of IHC markers comparing ONC and CHR using a digital imaging system and hierarchical clustering analysis.
Design: Tissue microarray (TMA) sections composed of 61 CHR, 34 ONC, and 12 normal kidneys were evaluated with a panel of markers previously reported to help distinguish ONC from CHR: CK7, claudin 7, vimentin, cyclin-D1, and H2AF. An additional marker identified by microarray analysis, SYNPR3, was also evaluated. Slides were scanned and staining intensity was determined by the ChromoVision Automatic Cellular Imaging System (ACIS II). Hierarchical clustering analysis was performed using MayDay microarray data analysis software.
Results: Clustering analysis using the full panel of 6 markers did not separate ONC from CHR. However, using a 2 marker panel of CK7 and Claudin 7, clustering analysis distinguished CHR, ONC, and normal kidney. The dendrogram showed 4 clusters: ONC, normal kidney, and two discrete clusters of CHR. The majority of ONC (29 of 34) clustered together. Most normal kidney samples (9 of 12) clustered together. The majority of CHR clustered together on one branch (44 of 61), while a separate group of 8 cases clustered together on a different branch which was more closely related, by branch node, to the ONC. Histologically, these 8 cases were classic CHR. Further, the difference in mean staining intensity of ONC and CHR was statistically significant for both CK7 (p<0.001) and Claudin 7 (p<0.001).
Conclusions: Digital imaging and hierarchical clustering analysis provides a more objective measure of an immunomarker in distinguishing oncocytoma from chromophobe RCC. We found that a panel of CK7 and Claudin 7 established a staining signature that can distinguish oncocytoma from chromophobe RCC by hierarchical clustering. This was superior to an extended 6 marker panel, in which the staining patterns of the additional 4 markers did not generate sufficient distinguishing power. This method is promising as an aid in establishing accurate diagnoses, although further study is needed to evaluate the clinical utility of these findings.
Category: Genitourinary (including renal tumors)
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 118, Monday Morning