Class III β-tubulin, a marker of resistance to paclitaxel, is overexpressed in pancreatic ductal adenocarcinoma and intraepithelial neoplasia

K. M. Lee, D. Cao, A. Itami, P. M. Pour, Ralph H Hruban, A. Maitra, M. M. Ouellette

Research output: Contribution to journalArticle

Abstract

Aims: Class III β-tubulin (TUBB3) reduces microtubule stability and confers resistance to microtubule-stabilizing taxanes, including paclitaxel and docetaxel. Pancreatic ductal adenocarcinomas show limited responsiveness to taxanes, but little is known of the underlying mechanisms. The aim of this study was to examine TUBB3 expression in pancreatic cancer cell lines, invasive pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia (PanIN). Methods and results: Reverse transcriptase-polymerase chain reaction and Western blot were used to study TUBB3 expression in pancreatic cancer cell lines. Immunohistochemistry was employed to assess TUBB3 in pancreatic cancer specimens, including 75 invasive adenocarcinomas and 41 PanIN precursor lesions. TUBB3 was undetectable in non-neoplastic ducts of the pancreas. In contrast, the vast majority (78-93%) of pancreatic ductal adenocarcinomas demonstrated either diffuse or focal TUBB3 expression. TUBB3 was found to increase progressively in PanIN lesions from 3/16 of PanIN-1 (19%), 5/17 of PanIN-2 (29%) to 5/8 of PanIN-3 lesions (63%). Conclusions: TUBB3 is expressed in most pancreatic ductal adenocarcinomas, possibly accounting for the suboptimal response of these tumours to microtubule-stabilizing agents. Up-regulation of TUBB3 in PanIN lesions suggests that microtubule dysfunction is an early feature of this disease. TUBB3 immunohistochemistry could potentially help identify pancreatic cancer patients lacking TUBB3 expression who might benefit from taxane therapy.

Original languageEnglish (US)
Pages (from-to)539-546
Number of pages8
JournalHistopathology
Volume51
Issue number4
DOIs
StatePublished - Oct 2007

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Tubulin
Paclitaxel
Pancreatic Neoplasms
Microtubules
Neoplasms
Adenocarcinoma
Taxoids
docetaxel
Immunohistochemistry
Cell Line
Adenocarcinoma in Situ
Excipients
Reverse Transcriptase Polymerase Chain Reaction
Pancreas
Up-Regulation
Western Blotting

Keywords

  • Cancer
  • Docetaxel
  • Paclitaxel
  • Pancreatic
  • PanIN
  • Resistance
  • Tubulin

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Cell Biology

Cite this

Class III β-tubulin, a marker of resistance to paclitaxel, is overexpressed in pancreatic ductal adenocarcinoma and intraepithelial neoplasia. / Lee, K. M.; Cao, D.; Itami, A.; Pour, P. M.; Hruban, Ralph H; Maitra, A.; Ouellette, M. M.

In: Histopathology, Vol. 51, No. 4, 10.2007, p. 539-546.

Research output: Contribution to journalArticle

Lee, K. M. ; Cao, D. ; Itami, A. ; Pour, P. M. ; Hruban, Ralph H ; Maitra, A. ; Ouellette, M. M. / Class III β-tubulin, a marker of resistance to paclitaxel, is overexpressed in pancreatic ductal adenocarcinoma and intraepithelial neoplasia. In: Histopathology. 2007 ; Vol. 51, No. 4. pp. 539-546.
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abstract = "Aims: Class III β-tubulin (TUBB3) reduces microtubule stability and confers resistance to microtubule-stabilizing taxanes, including paclitaxel and docetaxel. Pancreatic ductal adenocarcinomas show limited responsiveness to taxanes, but little is known of the underlying mechanisms. The aim of this study was to examine TUBB3 expression in pancreatic cancer cell lines, invasive pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia (PanIN). Methods and results: Reverse transcriptase-polymerase chain reaction and Western blot were used to study TUBB3 expression in pancreatic cancer cell lines. Immunohistochemistry was employed to assess TUBB3 in pancreatic cancer specimens, including 75 invasive adenocarcinomas and 41 PanIN precursor lesions. TUBB3 was undetectable in non-neoplastic ducts of the pancreas. In contrast, the vast majority (78-93{\%}) of pancreatic ductal adenocarcinomas demonstrated either diffuse or focal TUBB3 expression. TUBB3 was found to increase progressively in PanIN lesions from 3/16 of PanIN-1 (19{\%}), 5/17 of PanIN-2 (29{\%}) to 5/8 of PanIN-3 lesions (63{\%}). Conclusions: TUBB3 is expressed in most pancreatic ductal adenocarcinomas, possibly accounting for the suboptimal response of these tumours to microtubule-stabilizing agents. Up-regulation of TUBB3 in PanIN lesions suggests that microtubule dysfunction is an early feature of this disease. TUBB3 immunohistochemistry could potentially help identify pancreatic cancer patients lacking TUBB3 expression who might benefit from taxane therapy.",
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AU - Pour, P. M.

AU - Hruban, Ralph H

AU - Maitra, A.

AU - Ouellette, M. M.

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