Histopathologic evaluation of stepwise progression of pancreatic carcinoma with immunohistochemical analysis of gastric epithelial transcription factor SOX2: comparison of expression patterns between invasive components and cancerous or nonneoplastic intraductal components.
OBJECTIVE
The purpose of this study was to perform histopathologic and immunohistochemical analyses of gastric transcription factor SOX2 and gastric mucin MUC5AC to better understand the stepwise progression of pancreatic carcinoma.


METHODS
Twenty-eight representative sections from 14 surgically resected pancreatic carcinomas were assessed microscopically. Sites of pancreatic intraepithelial neoplasia (PanIN) were counted, and histologic subtypes of invasive ductal carcinoma (IDC) were determined. The expression of SOX2 and MUC5AC in PanIN and IDC was examined immunohistochemically.


RESULTS
One hundred thirty-eight PanINs were identified. In 4 of the 14 cases, gradual transition from PanIN-1A to PanIN-3 was observed in a single duct, suggesting stepwise progression. The expression of MUC5AC increased with the progression of lesions from PanIN-1A to PanIN-3. SOX2 was expressed in only 6 of 107 early PanINs (5.8%). Out of 31 PanIN-3s, 7 were positive (22.6%), and SOX2 protein was localized in the nuclei of cells of the basal epithelium or in the vicinity of luminal necrosis. In addition, SOX2 was frequently and strongly expressed in poorly differentiated (57.1%) and neurally invasive (63.6%) components.


CONCLUSIONS
The results of our histopathologic examinations suggest that PanIN progresses stepwise to IDC. Immunohistochemistry results suggest that SOX2 is involved in later events of carcinogenesis.
Department of Surgical Oncology, Research Institution for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Hiroshima 734-8551, Japan. ysanadasurg@hotmail.com
Yuichi
Y
Sanada
Kazuhiro
K
Yoshida
Masahiro
M
Ohara
Mamoru
M
Oeda
Kazuo
K
Konishi
Yasuhiro
Y
Tsutani
D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D024002:HMGB Proteins / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D055271:Mucin 5AC; D009077:Mucins; D009361:Neoplasm Invasiveness; D010183:Pancreatic Ducts / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D012189:Retrospective Studies; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors / Q000235:genetics*
D024002:HMGB Proteins; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors