Phenotypic diversity of intrahepatic and extrahepatic cholangiocarcinoma on aspiration cytology and core needle biopsy

Chaudhary, Humera; Bhanot, Punam; Logroño, Roberto

doi:10.1002/cncr.21155

Cited by 17 publications

(1 citation statement)

References 34 publications

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“…A6 labeled all normal biliary epithelial cells in the wild-type liver ( Figure 3A) and the neoplastic cells in the Smad4 Co/Co Pten Co/Co Alb-Cre liver ( Figure 3B), suggesting oval cell or bile duct differentiation of the tumors. Next, we used a panel of markers that have been used for CC diagnosis, including CK19 (36), AE1 (36), Mucicarmine (37), and Mucin 5AC (38). Our analysis indicated that all tumors expressed these markers (Figure 3, C-G).…”

Section: Disruption Of Smad4 Andmentioning

confidence: 89%

Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption ofSmad4 andPten in mice

Kobayashi

Qiao

et al. 2006

Journal of Clinical Investigation

186

151

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Cholangiocellular carcinoma (CC), the second most common primary liver cancer, is associated with a poor prognosis. It has been shown that CCs harbor alterations of a number of tumor-suppressor genes and oncogenes, yet key regulators for tumorigenesis remain unknown. Here we have generated a mouse model that develops CC with high penetrance using liver-specific targeted disruption of tumor suppressors SMAD4 and PTEN. In the absence of SMAD4 and PTEN, hyperplastic foci emerge exclusively from bile ducts of mutant mice at 2 months of age and continue to grow, leading to tumor formation in all animals at 4-7 months of age. We show that CC formation follows a multistep progression of histopathological changes that are associated with significant alterations, including increased levels of phosphorylated AKT, FOXO1, GSK-3β, mTOR, and ERK and increased nuclear levels of cyclin D1. We further demonstrate that SMAD4 and PTEN regulate each other through a novel feedback mechanism to maintain an expression balance and synergistically repress CC formation. Finally, our analysis of human CC detected PTEN inactivation in a majority of p-AKT-positive CCs, while about half also lost SMAD4 expression. These findings elucidate the relationship between SMAD4 and PTEN and extend our understanding of CC formation.

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Section: Disruption Of Smad4 Andmentioning

confidence: 89%

Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption ofSmad4 andPten in mice

Kobayashi

Qiao

et al. 2006

Journal of Clinical Investigation

186

151

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Documentation of immunocytochemistry controls in the cytopathologic literature: A meta‐analysis of 100 journal articles

Colasacco

Mount

Leiman

2011

Diagnostic Cytopathology

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Although a detailed description of the procedure and tissue used as controls is considered a necessary component in surgical pathology articles in which immunohistochemistry is utilized, such documentation seems less stringent in the cytopathologic literature. A comprehensive literature search was done for articles published in English within the last 15 years on nine of the most widely used antibodies in cytopathology. Individual case reports were excluded. Of the 100 articles reviewed, 13 articles were review articles or commentaries and hence not included in the analysis. Only 11 (13%) of the remaining 87 articles described positive and negative controls run on identically prepared samples. Forty-seven articles (54%) either did not mention controls or did not run controls as separate specimens. Sixteen articles (18%) included a vague statement about controls. Twelve (14%) commented only on the negative control, included only histology tissue controls, or included cell block controls, but the study also included other types of preparations, such as cytospins. One article (1%) did not include controls because of insufficient material. The College of American Pathologists recognizes the impracticality of maintaining separate positive control samples for every possible combination of fixation, processing, and specimen type. However, more stringent documentation of procedure and use of controls in the cytopathologic literature will ensure that immunocytochemistry results in diagnostic cytopathology as well as in research are valid and reproducible.

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Essential Cytopathology Concepts for the Endosonographer

2015

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Phenotypic diversity of intrahepatic and extrahepatic cholangiocarcinoma on aspiration cytology and core needle biopsy

Cited by 17 publications

References 34 publications

Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption ofSmad4 andPten in mice

Induction of intrahepatic cholangiocellular carcinoma by liver-specific disruption ofSmad4 andPten in mice

Documentation of immunocytochemistry controls in the cytopathologic literature: A meta‐analysis of 100 journal articles

Essential Cytopathology Concepts for the Endosonographer

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