Comprehensive Analysis of Cathepsin K Expression in Human Neoplasms
Gang Zheng, Guido Martignoni, Cristina Antonescu, Elizabeth Montgomery, Charles Eberhart, George Netto, Janis Taube, William Westra, Jonathan Epstein, Tamara Lotan, Anirban Maitra, Edward Gabrielson, Michael Torbenson, Chris Iacobuzio-Donahue, Angelo Demarzo, Ie Ming Shih, Peter Illei, Douglas Clark, TC Wu, Pedram Argani. Johns Hopkins Hospital, Baltimore, MD; University of Verona, Verona, Italy; Memorial Sloan-Kettering Cancer, New York
Background: Cathepsin K is a papain-like cysteine protease which is responsible for degradation of collagen type 1 and other bone proteins. Cathepsin K is expressed in osteoclasts under the control of Microphthalmia Transcription Factor (MiTF), and has been shown to be expressed in melanoma which is also MiTF positive. We have recently shown that Cathepsin K is consistently and diffusely expressed in alveolar soft part sarcoma (ASPS) and a subset of translocation renal cell carcinomas (RCC) which overexpress gene fusions involving the related transcription factors TFE3 and TFEB, but is not expressed in conventional RCC. However, a systemic analysis of Cathepsin K expression in human neoplasms, particularly those in a differential diagnosis of ASPS and translocation RCC, has not been performed.
Design: We constructed tissue microarrays (TMA) from a wide variety of human neoplasms, spanning approximately 9000 spots from 1562 samples derived from 72 different tumor types. The TMA were labeled for Cathepsin K by immunohistochemistry. Labeling was scored for percentage labeling (0-100%) and intensity (0=none, 1=weak, 2=moderate, 3=strong), and these were multiplied to give an H-score (0-300). Labeling yielding an H score of 20 or more was considered positive.
Results: Only 2 of 956 carcinomas from various sites (0.2 %) were positive for Cathepsin K; almost all were completely negative. However, Cathepsin K was expressed in many non-epithelial lesions, some of which fall in differential diagnosis of ASPS. Notably, Cathepsin K was expressed in granular cell tumor (57% of cases), juvenile xanthogranuloma (78% of cases), and (as previously reported) melanoma (66% of cases). In contrast, clear cell sarcoma (12 cases), adrenal cortical neoplasms (36 cases) and paragangliomas (19 cases) were consistently negative for Cathepsin K.
Conclusions: Among carcinomas, Cathepsin K labeling is highly specific for translocation RCC. While it is a highly sensitive marker for ASPS, Cathepsin K labeling among soft tissue tumors is not specific, in that it is expressed in a variety of mesenchymal lesions, including some of those in morphological differential diagnosis of ASPS. In particular, Cathepsin K expression in granular cell tumor and histiocytic lesions warrants diagnostic caution. However, the absence of diffuse Cathepsin K expression in clear cell sarcoma, adrenal cortical neoplasms and paraganglioma can help distinguish these 3 lesions from ASPS.
Category: Bone & Soft Tissue
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 14, Monday Morning