Frequent and Specific Involvement of Changes of the p16–RB Pathway in Esophageal Neuroendocrine Carcinoma

KOICHIRO FUJIMASA; NOBUYUKI OHIKE; TOMOKO NOROSE; TOMOHIDE ISOBE; KAZUO KIKUCHI; KOJI OTSUKA; MASAHIKO MURAKAMI; MASAFUMI TAKIMOTO

doi:10.21873/anticanres.13302

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Figure 1.
Esophageal neuroendocrine carcinoma (NEC). A: Solid sheets of NEC cells (asterisk). Arrows indicate coexisting intraepithelial carcinoma. hematoxylin and eosin staining, ×12.5 B: Diffuse loss of retinoblastoma protein in NEC, but not in intra-epithelial carcinoma. RB immunostaining, ×12.5. C: Diffuse overexpression of p16 protein in NEC as well as in intraepithelial carcinoma. p16 immunostaining, ×12.5.
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Figure 2.
Esophageal neuroendocrine carcinoma (NEC). A: Small-cell NEC of fusiform nuclei with finely granular chromatin, scant cytoplasm, and nuclear molding. Hematoxylin and eosin staining, ×400. B: Diffuse loss of nuclear expression of retinoblastoma protein. Note positive nuclear staining in endothelial cells as an internal control. Retinoblastoma immunostaining, ×400. C: Diffuse overexpression of p16 protein in the nucleus and cytoplasm. p16 immunostaining, ×400.
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Figure 3.
Esophageal mixed-type neuroendocrine carcinoma (so-called MANEC). A: A mixture of tubular adenocarcinoma (upper right) and large-cell NEC (asterisk). hematoxylin and eosin staining, ×400. B: Diffuse positivity (no loss) of retinoblastoma protein. Retinoblastoma immunostaining, ×400 C: Diffuse negativity (no overexpression) of p16 protein. p16 immunostaining, ×400.
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Figure 4.
Esophageal neuroendocrine carcinoma (NEC) and coexisting intraepithelial carcinoma. A: Small-cell NEC (right) and coexisting intraepithelial carcinoma (asterisk). Hematoxylin and eosin staining, ×400. B: Diffuse loss of retinoblastoma protein in NEC, but not in intraepithelial carcinoma. Retinoblastoma immunostaining, ×400. C: Diffuse overexpression of p16 protein in NEC as well as in intraepithelial carcinoma. p16 immunostaining, ×400.
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Figure 5.
Esophageal neuroendocrine carcinoma (NEC) and coexisting intraepithelial carcinoma. A: Small-cell NEC (right) and coexisting intraepithelial carcinoma (asterisk). Hematoxylin and eosin staining, ×400. B: Diffuse loss of retinoblastoma protein in NEC as well as in intraepithelial carcinoma. Retinoblastoma immunostaining, ×400. C: Diffuse overexpression of p16 protein in NEC as well as in intraepithelial carcinoma. p16 immunostaining, ×400.