Expression of nerve growth factor and tyrosine kinase receptor A and correlation with perineural invasion in pancreatic cancer

J Gastroenterol Hepatol. 2008 Dec;23(12):1852-9. doi: 10.1111/j.1440-1746.2008.05579.x.


Background and aim: Perineural invasion (PNI) is one of the most common routes of invasion in pancreatic cancer and the exact mechanism is still not clear. The aim of the present study was to investigate the effect of nerve growth factor (NGF) and tyrosine kinase receptor A (TrkA) on PNI and to clarify the possible mechanism of PNI in pancreatic cancer.

Methods: Expressions of NGF/TrkA were examined in 51 human primary pancreatic cancer using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). The molecular findings were correlated with PNI, clinicopathological parameters and expression of Ki-67.

Results: Immunohistochemical analysis indicated that the presence and kind of PNI are prognostic parameters (P = 0.002,, P = 0.004). Tumors with high NGF expression exhibited more frequent presence of PNI (P = 0.033). NGF expression was significantly correlated with metastasis of lymph nodes and involvement of surgical margins (P = 0.006, 0.015). TrkA expression was significantly correlated with degree of PNI (P = 0.017). Negative correlations were found between expression of NGF/TrkA and Ki-67. As shown by RT-PCR, mRNA levels of NGF/TrkA with PNI were significantly higher than that without PNI.

Conclusions: In pancreatic cancer, overexpression of NGF may contribute to PNI by prompting the hyperplasia of nerves, restraining the apoptosis of tumor cells and specifically combining NGF and TrkA.

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hyperplasia
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Nerve Growth Factor / analysis*
  • Nerve Growth Factor / genetics
  • Pancreatic Neoplasms / chemistry*
  • Pancreatic Neoplasms / enzymology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy
  • Peripheral Nerves / pathology*
  • RNA, Messenger / analysis
  • Receptor, trkA / analysis*
  • Receptor, trkA / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Treatment Outcome


  • Biomarkers, Tumor
  • Ki-67 Antigen
  • RNA, Messenger
  • Nerve Growth Factor
  • Receptor, trkA