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

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

来源：Modern Pathology, 2017, 30(5): 660-671.

DOI：10.1038/modpathol.2016.222

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.

• 出版日期2017-5