Primary Clear Cell Renal Cell Carcinoma and Its Metastasis: A Comparative Analysis of Histologic and Immunophenotypic Features
Elizabeth M Genega, Victoria E Brown, Brittany Bahamon, Ashley Ward, Liza Quintana, Sabina Signoretti. Beth Israel Deaconess Medical Center, Boston, MA; Brigham & Women's Hospital, Boston, MA
Background: Clear cell renal cell carcinoma (CCRCC), the most common type of RCC and the type that most frequently metastasizes, is a heterogeneous neoplasm with significant variability in its histologic features within a given tumor and amongst tumors. The study of predictive and/or prognostic tissue biomarkers for metastatic CCRCC is usually conducted by analyzing the primary tumor, which is more readily available, rather than the metastases (METS) that are targeted by systemic therapy. However, it is not known to what extent the primary tumor is representative of its metastatic lesions. In this study, we evaluated and compared histological and immunophenotypic features in a series of primary CCRCCs and their METS.
Design: Slides and tissue blocks from primary CCRCCs and their METS were retrieved. Histologic features, including predominant and highest Fuhrman grade (1-2 = low FG; 3-4 = high FG) and growth pattern (GP), were compared in the primary tumor (PT) and the corresponding METS. Carbonic anhydrase IX (CAIX) immunostaining was performed on one or more representative sections of the primary and metastatic tumors using the M75 antibody. Additional biomarkers are currently under evaluation.
Results: Twenty patients were identified, 3 had metachronous METS, 16 had synchronous METS and one had both. Twenty-nine METS were found: 4 adrenal METS, 5 lymph node METS, and 20 distant METS. All PT were high FG; 12 had a highest FG (HFG) = 3 and 8 had a HFG = 4. The predominant FG (PFG) of the PT was 2 in 9 cases, 3 in 10 cases and 4 in one case. Twenty-five METS were also high FG (12 with HFG = 3 and 13 with HFG = 4). The remaining 4 METS had HFG = 2. In 19 METS, the HFG matched the HFG of the corresponding PT, while in 5 METS the HFG matched the PFG of the corresponding PT. The HFG of the remaining 5 METS was higher than the HFG of the PT. Assessment of the GP revealed that in 25 METS the GP matched that of the PT and in 2 cases it did not; the GP of two METS was not evaluable. Immunohistochemical analysis of the METS (n=24) and corresponding PT (n=20) revealed CAIX expression was concordant (ie. +/- 10% positive cells) in 21 of 24 METS.
Conclusions: 1. For CCRCC that metastasize, the PFG and HFG of the PT is more often high grade. 2. The majority of CCRCC METS (83%) had a high FG component that matched the HFG of the corresponding PT or was higher. 3. The vast majority of CCRCC METS (88%) showed CAIX levels similar to those observed in the corresponding PT.
Category: Genitourinary (including renal tumors)
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 106, Wednesday Morning