Abstract
Considering the specific clinical management of neuroendocrine (NE) neoplasms (NENs), immunohistochemistry (IHC) is required to confirm their diagnosis. Nowadays, synaptophysin (SYP), chromogranin A (CHGA), and CD56 are the most frequently used NE immunohistochemical markers; however, their sensitivity and specificity are less than optimal. Syntaxin 1 (STX1) is a member of a membrane-integrated protein family involved in neuromediator release, and its expression has been reported to be restricted to neuronal and NE tissues. In this study, we evaluated STX1 as an immunohistochemical marker of NE differentiation. STX1, SYP, CHGA, and CD56 expression was analyzed in a diverse series of NE tumors (NETs), NE carcinomas (NECs), and non-NE tumors. All but one (64/65; 98%) NETs and all (54/54; 100%) NECs revealed STX1 positivity in at least 50% of the tumor cells. STX1 showed the highest sensitivity both in NETs (99%) and NECs (100%) compared to CHGA (98% and 91%), SYP (96% and 89%), and CD56 (70% and 93%), respectively. A wide variety of non-NE tumors were tested and found to be uniformly negative, yielding a perfect specificity. We established that STX1 is a robust NE marker with an outstanding sensitivity and specificity. Its expression is independent of the site and grade of the NENs.
Highlights
Neuroendocrine (NE) cells comprise a cellular network integrating the nervous and endocrine systems
CD56 is highly sensitive to NE cells [4]; it is detectable in a heterogeneous group of non-NE neoplasms, including nephroblastoma, neuroblastoma, myeloid, lymphoid, and plasma cell tumors, as well as in hepatocellular, renal cell, ovarian, endometrial, and thyroid carcinomas [25,26]
Using a well-characterized monoclonal mouse antibody, we found that Syntaxin 1 (STX1) represents an impressive robust NE marker, with a sensitivity of 99% in NE tumors (NETs) and 100% in NE carcinomas (NECs), outperforming other common NE markers, such as SYP (96% and 89%), chromogranin A (CHGA) (93% and 91%), and CD56 (70% and 93%), which was proven to be statistically significant regarding gastrointestinal NETs and NECs
Summary
Neuroendocrine (NE) cells comprise a cellular network integrating the nervous and endocrine systems. They are found in virtually all organs, and the most common are in the gastrointestinal and lower respiratory tracts. The NE cells secrete biogenic amines and peptide hormones regulating a wide variety of functions into the bloodstream. Tumorous growths of NE cells are collectively referred to as NE neoplasms (NENs). The bioactive substances secreted by neoplastic NE cells can lead to distinct clinical syndromes. There are many organ-specific differences in tumor biology and prognostic factors among NENs of different localizations, according to the recommendations of the International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal, the terminology of NENs should be uniformized in the future.
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