title: SOX2 and Rb1 in esophageal small-cell carcinoma: their possible involvement in pathogenesis.
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.
authors.affiliation: Division of Advanced Surgical Science and Technology, Miyagi, Japan.|Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kasajima
authors.affiliation: Division of Advanced Surgical Science and Technology, Miyagi, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kamei
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miura
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.|Department of Pathology and Laboratory Medicine, National Hospital Organization Sendai Medical Center, Miyagi, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Oka
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Yazdani
authors.affiliation: Division of Advanced Surgical Science and Technology, Miyagi, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Fujishima
authors.affiliation: Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Miyagi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Sakurada
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Division of Gastroenterological Surgery, Saitama, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Pathology, Saitama Cancer Center, Saitama, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kurosumi
authors.affiliation: Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Miyagi, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Division of Advanced Surgical Science and Technology, Miyagi, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ohuchi
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D018288:Carcinoma, Small Cell / Q000378:metabolism / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D056286:Retinoblastoma Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D055748:SOXB1 Transcription Factors / Q000032:analysis / Q000096:biosynthesis*; D055752:Small Cell Lung Carcinoma / Q000378:metabolism / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; D055748:SOXB1 Transcription Factors; D044767:Ubiquitin-Protein Ligases