ISL1 and neoplasm: For example, positivity for CGA, SYP, ISL1, INSM1, and SECG was a common profile for Pan-NENs irrespectively of tumor grade or tumor site (primary lesion vs. metastatic lesion), while an immunohistochemical profile consisting of a negative ISL1 staining adjoined by positivity for other neuroendocrine markers of both the first- and second-generation would strongly suggest an origin in the small intestine or appendix.