Re-Visiting the Use of Common Biomarkers in Cytogenetically Confirmed Subtypes of Renal Epithelial Neoplasia
Trevor Flood, Paola Dal Cin, Michelle S Hirsch. Brigham & Women's Hospital, Boston, MA
Background: There is great variability in the reported protein expression patterns in renal epithelial neoplasms (RENs). One explanation is that newer REN subtypes, such as clear cell tubulopapillary renal cell carcinoma (CCTPRCC) and mucinous tubular and spindle cell carcinoma (MTSCC), were misclassified as clear cell renal cell carcinoma (CCRCC) and/or papillary renal cell carcinoma (PRCC), affecting the data. The goal of this study was to revisit the diagnostic utility of common antibodies in cytogenetically confirmed RENs to determine more accurate specificity, sensitivity, and clinical use of these markers.
Design: IHC with CK7, AMACR, and CD117 (cKIT) was performed on 100 RENs with classic confirmatory karyotypes, including 53 CCRCC with loss of chromosome 3p, 22 PRCC with trisomies 7 and 17, 9 chromophobe carcinomas (ChRCCs) with multiple monosomies, 5 oncocytomas (RO) with loss of chromosome 1, and 5 MTSCCs with specific monosomies. Additionally, 6 CCTPRCCs with classic morphologic features were evaluated. IHC staining of tumors were assessed independently and semi-quantitatively by 2 pathologists: 0 no reactivity; 1+ <10%; 2+ 11–25%; 3+ 26-50%; and 4+ >50%; a score of ≥2+ was considered a positive result.
Results: Rare cases of CCRCCs were positive for CK7 (6/53, two 3+, four 4+) and CD117 (1/53); whereas AMACR staining was present in 64% (34/53) of cases. Of the 6 CK7+ CCRCCs, 3 were AMACR positive and 3 were negative. Most PRCCs showed strong staining for CK7 (18/22) and AMACR (21/22) with few cases expressing CD117 (2/22). All CK7 negative PRCCs were of the 'type II' variant, were positive for AMACR, and negative for CD117. Approximately half of the ChRCCs were positive for CK7 (5/9) and CD117 (4/9) with AMACR usually absent (1/9 positive). All 5 ROs were negative for both CK7 and AMACR, but positive for CD117. CK7 and AMACR were positive in 2/5 and 4/5 MTSCCs, respectively; none were positive for CD117. All 6 CCTPRCCs were diffusely positive for CK7 and completely negative for AMACR.
Conclusions: To our knowledge this is the first study that has determined the diagnostic value of certain IHC markers on cytogenetically confirmed subtypes of RENs. Overall the data shows that when morphologic findings in RENs overlap, variable expression patterns of CK7, AMACR and CD117 can be useful adjuncts. A CK7+/AMACR- finding is sensitive and specific for CCTPRCC (6/6, 100%) and argues against CCRCC (3/53, 6%) and PRCC (1/22). Additionally, the presence of CD117 can reliably help distinguish RO from PRCC and MTSCC, both of which can demonstrate onco1ytic features, but not from ChRCC.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:15 AM
Platform Session: Section A, Monday Morning