KIT is an independent prognostic marker for pancreatic endocrine tumors: A finding derived from analysis of islet cell differentiation markers

Lizhi Zhang, Thomas Christopher Smyrk, Andre M. Oliveira, Christine M. Lohse, Shuya Zhang, Michele R. Johnson, Ricardo V. Lloyd

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Prediction of the biologic behavior of pancreatic endocrine tumor (PET) without local invasion or metastasis is often difficult. The 2004 World Health Organization (WHO) classification uses size, angioinvasion, mitotic activity, and Ki-67 index as prognostic criteria. Recently, cytokeratin 19 (CK19) was shown to be another prognostic marker, but the mechanism by which CK19 predicts prognosis is unknown. As CK19 is the first cytokeratin expressed in all epithelial cells in fetal pancreas, we sought to test expression of other markers of islet cell differentiation including KIT, Pdx-1, Pax4, and Pax6 in PET and correlation of these markers with clinical behavior. Clinical information and histology was reviewed in 97 PETs. All tumors were classified according to WHO criteria and a tumor, node, and metastases stage system. Immunohistochemistry was performed using antibodies to Ki-67, KIT, CK19, Pdx-1, Pax4, and Pax6. Associations of clinicopathologic and immunohistochemical features with prognosis were evaluated using Cox proportional hazards regression models. WHO and tumor, node, and metastases classifications, mitotic counts and Ki-67 labeling, infiltrative border, necrosis, perineural invasion, extrapancreatic extension, tumor size, and positive CK19 and KIT expression were significantly associated with death from disease in a univariate setting. In multivariate analysis, only WHO criteria and KIT expression were shown to be independent. An immunohistochemical classification system was derived from a combination of KIT and CK19 expression: low risk (KIT-/CK19-), intermediate risk (KIT-/CK19+), and high risk (KIT+/CK19+). Survival, metastases, and recurrence of PET were significantly different among the 3 groups. These results indicate that KIT is a new and independent prognostic marker for PETs. The classification system derived from KIT and CK19 was able to predict clinical behavior of PET.

Original languageEnglish (US)
Pages (from-to)1562-1569
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume33
Issue number10
DOIs
StatePublished - Oct 2009

Fingerprint

Keratin-19
Differentiation Antigens
Islets of Langerhans
Cell Differentiation
Neoplasms
Neoplasm Metastasis
Tumor Biomarkers
Keratins
Proportional Hazards Models
Pancreas
Histology
Necrosis
Multivariate Analysis
Epithelial Cells
Immunohistochemistry

Keywords

  • CK19
  • KIT
  • Pancreatic endocrine tumor

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

KIT is an independent prognostic marker for pancreatic endocrine tumors : A finding derived from analysis of islet cell differentiation markers. / Zhang, Lizhi; Smyrk, Thomas Christopher; Oliveira, Andre M.; Lohse, Christine M.; Zhang, Shuya; Johnson, Michele R.; Lloyd, Ricardo V.

In: American Journal of Surgical Pathology, Vol. 33, No. 10, 10.2009, p. 1562-1569.

Research output: Contribution to journalArticle

Zhang, Lizhi ; Smyrk, Thomas Christopher ; Oliveira, Andre M. ; Lohse, Christine M. ; Zhang, Shuya ; Johnson, Michele R. ; Lloyd, Ricardo V. / KIT is an independent prognostic marker for pancreatic endocrine tumors : A finding derived from analysis of islet cell differentiation markers. In: American Journal of Surgical Pathology. 2009 ; Vol. 33, No. 10. pp. 1562-1569.
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AU - Lloyd, Ricardo V.

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