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Cytopathology. 2019 Mar;30(2):201-208. doi: 10.1111/cyt.12653. Epub 2018 Dec 18.

Abnormal immunolabelling of SMAD4 in cell block specimens to distinguish malignant and benign pancreatic cells.

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Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan.
Department of Endoscopy, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan.
Research Team for Geriatric Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi-ku, Tokyo, Japan.



Accurate diagnosis of malignant and benign pancreatic lesions can be challenging, especially with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples that are small and/or degraded. In the present study, we determined how to best evaluate abnormal SMAD4 expression by immunohistochemical staining on cell block specimens from EUS-FNA samples.


In surgically resected pancreas, when abnormal SMAD4 immunolabelling was evaluated as negative SMAD4 expression, the sensitivity was low (33%), but when it was evaluated as decreased SMAD4 expression, the sensitivity improved (53%). Specificity and positive predictive value were high for both evaluations. There were no false-positive cases. In cell block specimens, decreased SMAD4 expression showed 47% sensitivity and 72% specificity, while negative SMAD4 expression showed lower sensitivity (20%) and higher specificity (100%). Both evaluations in cell block specimens showed lower sensitivity and specificity compared to resected specimens. False-positive and -negative rates were higher for cell blocks than for resected specimens.


Decreased SMAD4 immunolabelling provided improved sensitivity as compared to negative SMAD4 immunolabelling; therefore, it is important to compare SMAD4 expression in a sample to its expression in normal cells. Abnormal SMAD4 labelling showed low sensitivity and high specificity; therefore, SMAD4 staining using EUS-FNA samples might be helpful to detect malignancies that possess SMAD4 gene abnormalities.


SMAD4; cell block; endoscopic ultrasound-guided fine needle aspiration; immunohistochemistry; pancreatic cancer


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