SOX11 is a sensitive and specific marker for pulmonary high-grade neuroendocrine tumors

Abstract

Background Synaptophysin (SYN), chromogranin A (CGA), CD56 and insulinoma-associated protein 1 (INSM1) are proposed neuroendocrine (NE) markers used for diagnosis of pulmonary NE tumors. These NE markers have been identified in subsets of non-NE tumors requiring differential diagnosis, thus we sought to explore new NE markers. Methods We evaluated the immunohistochemical expression of SOX11, a transcription factor involved in neurogenesis, in pulmonary NE tumors and large cell carcinomas (LCCs). Results We found that SOX11 showed a sensitivity similar to INSM1 and CGA, and less than SYN and CD56 in small cell lung carcinomas (SCLCs) and large cell neuroendocrine carcinomas (LCNECs). While SOX11 is more specific than the other four markers for diagnosis of high-grade neuroendocrine carcinomas (HG-NECs) because 1) None of LCCs (0/63), the most challenging non-NE tumor type for differential diagnosis due to overlapped morphology with LCNECs displayed SOX11 positivity. While expression of at least one of SYN, CGA, CD56 or INSM1 was identified in approximately 60% (18/30) of LCCs. 2) SOX11 was only expressed in 1 of 37 carcinoid tumors in contrast to diffuse expression of SYN, CGA, CD56 and INSM1. In HG-NECs, we noticed that SOX11 was a good complementary marker for SCLC diagnosis as it was positive in 7 of 18 SYN−/CGA−/CD56− SCLCs and 3 of 8 SYN−/CGA−/CD56−/INSM1− SCLCs, and SOX11 positivity in 4 of 6 SYN−/CGA−/CD56− cases previously diagnosed as LCCs with NE morphology provides additional evidence of NE differentiation for reclassification into LCNECs, which was further confirmed by electromicroscopical identification of neurosecretory granules. We also found SOX11 expression cannot predict the prognosis in patients with HG-NECs. Conclusions Therefore, SOX11 is a useful complementary transcriptional NE marker for diagnosis and differential diagnosis of SCLC and LCNEC.

Occult urothelial carcinoma with mediastinal metastasis: A case report

“…Thymic carcinoma is positive for CK5 and CD117 immunoreactivity (16). Established IHC markers for diagnosing neuroendocrine tumor neoplasms include Syn, CD56 and TTF-1, which demonstrate notable sensitivity and specificity in their diagnostic utility (17)(18)(19). IHC staining for GATA3 in mediastinal masses is not routinely performed by the Affiliated Hospital of Weifang Medical University (Weifang, China).…”

Immunocytochemical detection by a fully automated immunostainer for assisting subclassification of pulmonary tumors on ThinPrep slides in real‐life clinical samples: A single‐institution experience

“…are among the commonly used markers. 11,12 However, IC protocols are generally performed on formalin-fixed paraffin-embedded (FFPE) tissue. Hence, it is significant to validate IC protocols for these frequently used stains on ThinPrep slides.…”

“…Moreover, Napsin A for LUAD, p63 for LUSC, and synaptophysin (Syn) and CD56 for neuroendocrine tumors. are among the commonly used markers 11,12 . However, IC protocols are generally performed on formalin‐fixed paraffin‐embedded (FFPE) tissue.…”