Fig. 2

Intact Rb expression with negative high-risk human papillomavirus (HR-HPV) in a subset of left colon neuroendocrine carcinomas (NEC). This left colon neuroendocrine carcinoma (a−e, L7), representative of the second molecular subgroup in this study, had an associated adenocarcinoma (f−j). Both the neuroendocrine carcinoma and adenocarcinoma components demonstrated diffuse strong p53 (b, g) and intact Rb (c, h). The neuroendocrine carcinoma component had diffuse strong block-like p16 expression (d), whereas the adenocarcinoma had patchy strong p16 expression (i). Both components were negative for HR-HPV by in situ hybridization (ISH) and PCR (e, j). Four left colon neuroendocrine carcinomas with this staining pattern all demonstrated TP53 mutation and 3/4 had focal amplifications of CCNE1, MYC, MYCN, or TERT and 1/4 had SMARCB1 alteration (see Fig. 4) (Hematoxylin and eosin, a and f)