Identification and Validation of Immunohistochemical Markers To Discriminate Urothelial Carcinoma Invading the Prostatic Fibromuscular Stroma vs In-Situ Tumor of the Prostatic Ducts
Eric J Fichtenbaum, William L Marsh, Debra L Zynger. The Ohio State University, Columbus
Background: Within the prostate, discrimination between urothelial carcinoma (UC) invading the fibromuscular stroma (pT4a) versus in-situ tumor of the prostatic ducts can be difficult. The goal of this study was to assess immunohistochemical (IHC) markers for their use in determining depth of tumor invasion within the prostate.
Design: 9 cases with UC involving the prostate were used to screen candidate markers for utility in differentiating tumor depth (CK5/6, CK7, CK20, p53, p63, HMWK, androgen receptor (AR), PSA, PSAP, laminin, CD44, CD141). IHC was semi-quantitatively evaluated (0, <5%; 1+, 5-10%; 2+, 11-50%; or 3+, >50%). CK5/6 (Dako, D5/16B4) was identified as a promising marker. A retrospective review of cystoprostatectomies (CP) was performed to identify cases with UC involving the prostate upon which CK5/6 was assessed. CK5 (Novocastro, XM26), a recently available antibody requiring more moderate fixation conditions and a lower concentration compared to CK5/6 and thus ideal to use in double stains, was validated on the CP cases. Subsequently, the following double stain combinations were performed: CK5 (red)/p53 (brown), CK5 (brown)/p53 (red), CK5 (brown)/CK7 (red), CK5 (red)/CK7 (brown) and AR (brown)/CK7 (red).
Results: 41 CP with UC in the prostate were identified (in-situ tumor only, n=4; fibromuscular stroma invasion only, n=21; in-situ tumor and fibromuscular stroma invasion, n=16). Both CK5/6 and CK5 were able to clearly differentiate basal cells (CK5/6: 20/20; 3+, 100% and CK5: 20/20; 3+, 100%) surrounding in-situ tumor from UC within ducts (CK5/6: 12/20; 0, 40.0%; 1+, 20.0%; 2+ 25.0%; 3+, 15.0% and CK5: 5/20; 0, 75.0%; 1+, 5.0%; 2+, 5.0%; 3+, 15.0%). The remaining markers were not effective in determining depth of tumor invasion when used as a single stain. CK5 (brown)/CK7 (red) and CK5 (red)/p53 (brown) robustly color contrasted in-situ tumor from surrounding basal cells and were further validated in 19 cases. Basal cells were not visible using CK5 (red)/CK7 (brown) or AR (brown)/CK7 (red). CK5 (brown)/p53 (red) did allow in-situ and basal cell discrimination; however, the nuclei were more easily visible using CK5 (red)/p53 (brown).
Conclusions: In this study we recommend the use of either CK5 or CK5/6 as an IHC marker to assist in determining depth of UC invasion within the prostate. Additionally, we propose the double stain combinations of CK5 (brown)/CK7(red) and CK5(red)/p53(brown) to simultaneously highlight the in-situ tumor within prostatic ducts and the surrounding prostatic basal cells.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 154, Monday Morning