Strong and Diffuse Nuclear Staining for Phospho-c-Jun Distinguishes Clear Cell Renal Cell Carcinoma from Its Mimickers.
Eric T Miller, Matthew B Rettig, Clara E Magyar, Jiaoti Huang. UCLA David Geffen School of Medicine, Los Angeles, CA
Background: Classification of renal epithelial tumors continues to present daily challenges to practicing pathologists as the major histologic types have overlapping architectural and cytologic features. Immunohistochemical markers have proven useful in certain cases but none is absolutely sensitive and specific. Therefore, a panel of markers is often required and novel markers are still being developed to increase our ability in the accurate classification of equivocal cases.
The loss of VHL gene function contributes to the majority of clear cell renal cell carcinomas (ccRCC). Our recent molecular study of the signaling pathway reveals that loss of VHL function results in hyper-phosphorylation of c-Jun. As a commercial anti-p-c-Jun antibody works well in paraffin-embedded tissue sections, we studied its utility in distinguishing the major histologic types of renal epithelial tumors.
Design: We selected from archival files 20 cases of ccRCC, 20 cases of chromophobe RCC (chRCC), 20 cases of oncocytoma, and 6 cases of papillary type I RCC (pRCC). One representative section from each case was stained with an anti-p-c-Jun antibody (Cell Signaling Technology, #9261, used at 1:30) which gives a nuclear staining pattern in positive cells. Five random fields on each slide were manually scored for staining intensity (0 to 3+) and percentage of positive cells. The two parameters were multiplied to arrive at a final staining score ranging from 0 to 300. One way ANOVA test was used to compare the mean staining scores between ccRCC and other tumor types.
Results: As expected from the results of our molecular analysis, the tumor cells of ccRCC showed diffuse and strong nuclear staining for phosphor-c-Jun, while the staining in other tumors was negative or only weakly and focally present in the periphery of the tumors adjacent to non-neoplastic kidney. The staining score was 129.3 + 72.5 for ccRCC, 18.9 + 36.6 for chRCC, 28.2 + 25.9 for pRCC, and 3.3 + 7.9 for oncocytoma. The difference between ccRCC and each of the other renal epithelial tumor types was statistically significant (p<0.001).
Conclusions: 1. The results of immunohistochemical study confirm those of molecular pathway study showing that loss of VHL gene function in ccRCC results in increased phosphorylation of c-Jun, a proto-oncogene and an important transcription factor.
2. Immunohistochemical study for phospho-c-Jun can be used to distinguish ccRCC from its common mimickers with high sensitivity and specificity thus has important value in the differential diagnosis of renal epithelial tumors.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 113, Monday Morning