Loss of PTEN and increased pAKT expression distinguishes aggressive low-grade neuroendocrine tumors

Rajeswari Jayakumar, Sonali Lanjewar, Constantine A. Axiotis

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Abstract

A major problem in neuroendocrine pathology is the identification and separation of aggressive low-grade neuroendocrine tumors (LGNETs) from those with a benign or more indolent behavior. Presently there are no known morphologic or molecular parameters which can predict how localized LGNETs will behave. The phosphatase and tensin homolog (PTEN) gene negatively regulates the PI3K-AKT-mTOR pathway and inhibits neoplastic cell survival and proliferation and has recently been identified as a neuroendocrine tumor differentiation marker. We hypothesized loss of PTEN may also identify LGNETs that demonstrate aggressive behavior. We studied PTEN and pAKT expression in 18 LGNETs using specific monoclonal antibodies. Follow up was obtained for a minimum of five years on all patients. 8/18 cases had strong PTEN expression and showed no evidence of disease on >5 years follow-up. 10 cases demonstrated loss of PTEN expression; 9/10 had positive pAKT expression, and 7/9 had recurrence and/or metastases. Lung and appendiceal LGNETs uniformly had high PTEN expression and a markedly better prognosis than their gastroenteropancreatic (GEP) counterparts. Loss of PTEN correlated significantly with the positive expression of pAKT (P=0.0027) and aggressive behavior of LGNETs (p=0.0002). Loss of PTEN and increased pAKT correlated with the metastatic potential of LGNETs (p=0.0011 and 0.0248 respectively). Loss of PTEN and increased pAKT expression distinguishes aggressive LGNETs from those with more indolent behavior.

Original languageEnglish (US)
Pages (from-to)565-572
Number of pages8
JournalAnnals of Clinical and Laboratory Science
Volume48
Issue number5
StatePublished - Sep 1 2018
Externally publishedYes

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Neuroendocrine Tumors
Phosphoric Monoester Hydrolases
Tumors
Tensins
Differentiation Antigens
Pathology
Tumor Biomarkers
Phosphatidylinositol 3-Kinases
Cell Survival
Genes
Monoclonal Antibodies
Cells
Cell Proliferation
Neoplasm Metastasis
Recurrence
Lung

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology and Allergy
  • Pathology and Forensic Medicine
  • Immunology
  • Molecular Biology
  • Hematology
  • Clinical Biochemistry
  • Medical Laboratory Technology

Cite this

Loss of PTEN and increased pAKT expression distinguishes aggressive low-grade neuroendocrine tumors. / Jayakumar, Rajeswari; Lanjewar, Sonali; Axiotis, Constantine A.

In: Annals of Clinical and Laboratory Science, Vol. 48, No. 5, 01.09.2018, p. 565-572.

Research output: Contribution to journalArticle

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