Identification of a functional EGF-R/p60c-src/STAT3 pathway in colorectal carcinoma: analysis of its long-term prognostic value

Cancer Biomark. 2008;4(2):83-91. doi: 10.3233/cbm-2008-4204.


Aims: The Epidermal Growth Factor-Receptor (EGF-R) is frequently overexpressed in colorectal carcinoma (CRC) and patients can benefit from anti-EGF-R therapy. Yet, the relationship, within tumours, between EGF-R and the activity of downstream effectors such as the non-receptor tyrosine kinase p60c-src and the signal transducer and activator of transcription 3 (STAT3) has not been extensively analyzed.

Methods and results: We evaluated EGF-R, tyrosine 416-phosphorylated p60c-src (P-p60c-src), STAT3 and tyrosine 705-phosphorylated STAT3 (P-STAT3) on Tissue Micro Array (TMA) from 126 patients with CRC. Composite immunohistochemistry scores based on the intensity of labelling and the percentage of positive cells were determined on TMA for EGF-R, P-p60c-src, STAT3 and P- STAT3. A high score was found in 56%, 61%, 62% and 27% of the cases for EGF-R, P-p60c-src, STAT3 and P-STAT3 respectively. There was a significant correlation between EGF-R and P-p60c-src (p=0.006) and between P-p60c-src and P-STAT3 (p=0.0009). STAT3 was significantly correlated with vascular emboli (p=0.03) and perineural invasion (p=0.02).

Conclusions: The correlations between EGF-R, P-p60-src and P-STAT3 and some stage-related pathological features point to a critical role for a EGF-R-connected p60c-src-kinase-mediated pathway involving STAT3 and contributing to cell survival and proliferation within CRC tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • ErbB Receptors / metabolism*
  • Humans
  • Immunohistochemistry
  • Neoplasm Staging
  • Phosphorylation
  • Prognosis
  • Proto-Oncogene Proteins pp60(c-src) / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / physiology*
  • Tissue Array Analysis
  • Tyrosine / metabolism


  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tyrosine
  • ErbB Receptors
  • Proto-Oncogene Proteins pp60(c-src)