SOX2 and Rb1 in esophageal small-cell carcinoma: Their possible involvement in pathogenesis

Hirotaka Ishida, Atsuko Kasajima, Takashi Kamei, Tsuyoshi Miura, Naomi Oka, Samaneh Yazdani, Yohei Ozawa, Fumiyoshi Fujishima, Akira Sakurada, Yasuhiro Nakamura, Yoichi Tanaka, Masafumi Kurosumi, Yuichi Ishikawa, Yoshinori Okada, Noriaki Ohuchi, Hironobu Sasano

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6 Citations (Scopus)

Abstract

Clinicopathological features and pathogenesis of esophageal small-cell carcinoma remain unclear. We hypothesized common cellular origin and pathogenesis in small-cell carcinoma of esophagus and lung associated with SOX2 overexpression and loss of Rb1. Expression of squamous-basal markers (CK5/6 and p40), glandular markers (CK18 and CEA), SOX2, and Rb1 were evaluated in 15 esophageal small-cell carcinomas, 46 poorly differentiated squamous cell carcinomas, and 88 small-cell lung carcinoma, as well as 16 embryonic esophagus. Esophageal small-cell carcinoma expressed higher levels of glandular markers and lower levels of squamous-basal markers than poorly differentiated squamous cell carcinoma. No significant differences were observed in immunohistochemistry profiles between small-cell carcinoma of the esophagus and the lung. SOX2 expression was high in esophageal small-cell carcinoma (70%±33% of nuclei), small-cell lung carcinoma (70%±26%), and the embryonic esophagus (75%±4%), and it was significantly lower in poorly differentiated squamous cell carcinoma (29%±28%). Rb1 expression was significantly lower in esophageal small-cell carcinoma (0.3%±1%), small-cell lung carcinoma (2%±6%), and the embryonic esophagus (7%±5%), and it was significantly higher in poorly differentiated squamous cell carcinoma (51%±24%). The immunohistochemistry profiles of small-cell carcinoma of the esophagus and the lung are highly similar. The loss of Rb1 function is a key contributor to the pathogenesis of both neoplasms. In addition, SOX2 overexpression observed in esophageal and lung small-cell carcinoma as well as in the embryonic esophagus indicated that esophageal small-cell carcinoma may arise from embryonic-like stem cells in the esophageal epithelium. The two distinct differentiation patterns (neuroendocrine and glandular) of esophageal small-cell carcinoma further support the fact that SOX2 has a pivotal role in the differentiation of pluripotent stem cells into esophageal small-cell carcinoma cells.

Original languageEnglish
Pages (from-to)660-671
Number of pages12
JournalModern Pathology
Volume30
Issue number5
DOIs
Publication statusPublished - 2017 May 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Ishida, H., Kasajima, A., Kamei, T., Miura, T., Oka, N., Yazdani, S., Ozawa, Y., Fujishima, F., Sakurada, A., Nakamura, Y., Tanaka, Y., Kurosumi, M., Ishikawa, Y., Okada, Y., Ohuchi, N., & Sasano, H. (2017). SOX2 and Rb1 in esophageal small-cell carcinoma: Their possible involvement in pathogenesis. Modern Pathology, 30(5), 660-671. https://doi.org/10.1038/modpathol.2016.222