DOG1 Rescues Most CD117-Negative GISTs: A Report from an Italian Multi-Institutional Study (REGISTER Study)
S Rossi, C Cantaloni, C Sartor, E Bragantini, L Messerini, I Bearzi, G Mazzoleni, C Capella, G Arrigoni, A Sonzogni, C Gnocchi, S Romeo, L Toffolatti, M Barbareschi, PG Casali, AP Dei Tos. General Hospital, Treviso, Italy; General Hospital, Trento, Italy; Firenze University School of Medicine, Firenze, Italy; Ancona University School of Medicine, Ancona, Italy; General Hospital, Bolzano, Italy; Ospedale di Circolo e Fondazione Macchi, Varese, Italy; Istituto Scientifico H S. Raffaele, Milano, Italy; Ospedali Riuniti, Bergamo, Italy; Novartis Farma, Sarcoma Unit, Origgio, Italy; IRCCS Istituto NazionaleTumori, Milano, Italy
Background: DOG1 is an emerging highly specific and sensitive immunohistochemical marker of GISTs. The aim of our study was to confirm the diagnostic utility of this antibody in a large Italian multi-institutional GISTs series (REGISTER) and in particular its ability to discriminate GIST from GISTs mimics.
Design: Immunohistochemistry for DOG1 (1:400, WB pH6, clone SP31, ACZON) was performed on 42 tissue microarray (TMA) slides, which included 583 CD117-positive GISTs and 45 CD117-negative GISTs. Furthermore 4 TMA slides containing 73 mesenchymal tumours of the GI tract, including 21 leiomyomas, 16 leiomyosarcomas, 12 pleomorphic sarcomas and 10 desmoid fibromatoses, were also immunostained.
Results: DOG1 immunostaining was positive in 574 (98.5%) of CD117-positive GISTs and in 37 (82.2%) of the CD117-negative GISTs. The majority of the positive cases (96.2%) showed a diffuse and strong staining (Table 1). Of the 73 GISTs mimics, only 2 smooth muscle tumors proved to be DOG1 positive (Table 2).
Conclusions: DOG1 is expressed in most of CD117-negative GISTs, indicating its higher sensitivity as GIST marker. As a small subgroup of CD117-positive GISTs failed to stain with DOG1, the combination of CD117 and DOG1 is highly recommended for the diagnosis of GIST in daily practice.
|N of cases||histotype||DOG1 +ve, N (%)||DOG1 -ve, N (%)|
|21||leiomyomas||1 (4.8)||20 (95.2)|
|16||leiomyosarcomas||1 (6.2)||15 (93.8)|
|12||pleomorphic sarcomas NOS||0||12 (100)|
|10||desmoid fibromatoses||0||10 (100)|
|4||spindle cell sarcomas||0||4 (100)|
|N of GISTs cases||DOG1 +ve||DOG1 -ve|
|CD117 +ve GISTs||583||555 (95.2%)||19 (3.3%)||9 (1.5%)|
|CD117 -ve GISTs||45||33 (73.3%)||4 (8.9%)||8 (17.8%)|