Use of tissue microarrays and immunohistochemistry to standardize the diagnosis of gastrointestinal stromal tumors

• Published in: Pathology international 2010-11, Vol.60 (11), p.707-713
• Main Authors: Ogino, Jiro, Asanuma, Hiroko, Sakurai, Shinji, Matsuno, Yoshihiro, Miyokawa, Naoyuki, Yamashiro, Katsushige, Fukazawa, Yuichiro, Muraoka, Shunji, Iwaki, Yasuyuki, Kondo, Nobuo, Hasegawa, Tadashi
• Format: Article
• Language: English
• Subjects: Adult; Antibodies; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; c-Kit protein; CD34 antigen; concordance; Cytoplasm; Desmin; Desmin - genetics; Desmin - metabolism; gastrointestinal stromal tumor (GIST); Gastrointestinal Stromal Tumors - diagnosis; Gastrointestinal Stromal Tumors - genetics; Gastrointestinal Stromal Tumors - metabolism; Gastrointestinal tract; Humans; Immunohistochemistry; Leiomyosarcoma - diagnosis; Leiomyosarcoma - genetics; Leiomyosarcoma - metabolism; Mesenchyme; Mesentery; Mutation; PDGFRA; Platelet-derived growth factor receptors; Proto-Oncogene Proteins c-kit - genetics; Proto-Oncogene Proteins c-kit - metabolism; Proto-oncogenes; Receptor, Platelet-Derived Growth Factor alpha - genetics; Receptor, Platelet-Derived Growth Factor alpha - metabolism; Receptors, Platelet-Derived Growth Factor - genetics; Receptors, Platelet-Derived Growth Factor - metabolism; Retroperitoneum; S100 protein; S100 Proteins - genetics; S100 Proteins - metabolism; Sarcoma - diagnosis; Sarcoma - genetics; Sarcoma - metabolism; Schwann cells; Smooth muscle; spindle cell tumor; Tissue Array Analysis; tissue microarray; Tumors; Vimentin
• ISSN: 1320-5463; 1440-1827
• DOI: 10.1111/j.1440-1827.2010.02585.x

We assessed the concordance among seven general pathologists with respect to histologic diagnosis and interpretation of c‐kit proto‐oncogene (KIT) and platelet‐derived growth factor receptor alpha (PDGFRA) immunostaining of 36 cases of primary spindle‐cell tumor, predominantly of the gastrointestinal tract, mesentery, and retroperitoneum, based on review of a tissue microarray (TMA) subjected to immunohistochemistry with antibodies to KIT/CD117, PDGFRA, vimentin, desmin, smooth muscle action, CD34, and S‐100 protein. Tumors included 20 molecularly analyzed gastrointestinal stromal tumors (GISTs), 4 leiomyosarcomas, 4 schwannomas, 4 desmoid‐type fibromatoses, and 4 solitary fibrous tumors. The mean overall concordance with original diagnosis for each histologic type was 91.1%, with a mean kappa value of 0.91. With respect to PDGFRA immunostaining, the four GISTs with PDGFRA mutation were interpreted as cytoplasm positive, but the 16 GISTs with c‐kit mutation were interpreted as weak or positive. These results indicate that the overall concordance with original diagnosis in mesenchymal tumors with the use of immunohistochemical panels is high, despite the use of TMAs. To some extent, PDGFRA immunophenotyping may be useful in GISTs with PDGFRA mutation, but it was not highly reproducible or specific. Therefore, in KIT‐negative or weakly positive GISTs, mutation analysis will be required.