Diagnostic potential of a novel immunohistochemical marker, GFPT2, in differentiating mesothelioma from its morphological mimics

Histopathology 2025 December 15 [Link]

Jia Wei, Xiaofang Ma, Gang Chen, Yan Wang, Qinhe Fan, Qixing Gong

Abstract

Aims: Mesothelioma (MESO) is a rare and aggressive tumour originating from mesothelial cells, primarily affecting the pleura and peritoneum. Its diagnosis remains challenging due to non-specific clinical, radiological and histopathological features, compounded by morphological diversity and overlapping immunohistochemical profiles with other tumours. Building on our previous finding that GFPT2 is highly expressed in MESO tissues, we evaluated its diagnostic utility in distinguishing MESO from histological mimics.

Methods and results: We conducted an immunohistochemical analysis of GFPT2 in 101 MESO cases and 266 histological mimics, including 100 non-small cell lung cancer (NSCLC), 40 high-grade serous ovarian cancer (HGSOC), 6 epithelioid hemangioendothelioma (EHE), 33 solitary fibrous tumour (SFT), 23 aggressive fibromatosis (AF), 6 synovial sarcoma (SS), 7 dedifferentiated liposarcoma (DDLPS), 6 leiomyosarcoma (LMS), 4 malignant peripheral nerve sheath tumour (MPNST), 8 sarcomatoid carcinoma, 20 reactive mesothelial hyperplasia (RMH) and 13 well-differentiated papillary mesothelial tumour (WDPMT) cases. GFPT2 positivity was detected in 85.15% (86/101) of MESO cases, significantly higher than in RMH (0%, 0/20), WDPMT (0%, 0/13), NSCLC (0%, 0/100), HGSOC (0%, 0/40), EHE (16.7%, 1/6), SFT (0%, 0/33), AF (21.74%, 5/23), SS (0%, 0/6), LMS (0%, 0/6), MPNST (25%, 1/4) and sarcomatoid carcinoma (12.5%, 1/8). However, DDLPS (85.7%, 6/7) showed high GFPT2 positivity.

Conclusions: This study demonstrates GFPT2’s diagnostic utility in MESO, effectively overcoming tumour heterogeneity challenges. It distinguishes malignant mesothelial lesions from benign/borderline ones (RMH/WDPMT), differentiates epithelioid MESO from epithelioid malignances(NSCLC/HGSOC/EHE) and aids in sarcomatoid MESO versus spindle cell tumours (SFT/AF/SS/LMS/MPNST/sarcomatoid carcinoma), though limited for DDLPS. In summary, GFPT2 is a promising novel antibody demonstrating 85.2% sensitivity and 94.7% specificity.