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In fact, E-cadherin gene mutations have been detected in tumor cell lines, primary tumors and metastases from a variety of cancer types. Recent investigations have revealed another novel mechanism of gene inactivation, involving hypermethylation of the E-cadherin gene promoter region. Immunohistochemistry (IHC) has the advantage of detecting E-cadherin status irrespective of the mechanism of gene inactivation (allelic deletion, mutation or hypermethylation), thus providing more information than would be obtained by any single genetic analysis alone.
As many as 50% of diffuse type gastric carcinomas demonstrate E-cadherin mutations with IHC has shown complete loss of E-cadherin expression in such cases. In prostate cancers, one third of organ-confined cancers exhibit abnormal E-cadherin expression, while over 75% metastatic cancers demonstrate this abnormality, implicating a role in disease progression. Investigators have also demonstrated a correlation between loss of E-cadherin expression and higher Gleason grade prostate cancers. On similar lines, abnormal E-cadherin IHC is associated with an advanced Duke's stage and poor differentiation in colorectal cancers. In transitional cell carcinomas, E-cadherin downregulation correlates with poor outcome in multivariate analysis. E-cadherin IHC abnormalities have also been detected in non-small cell lung cancers, lobular breast carcinomas, and ovarian and endometrial carcinomas, and several studies exist within each cancer type, demonstrating the adverse clinical consequences of loss of E-cadherin expression by IHC.
Veripath OncoDiagnostics offers E-cadherin as part of the standard breast and stomach cancer panels, but it can also be ordered individually. Currently, we are using an automated image analysis system to quantitatively score percentage positivity and intensity grade finally reflected in a histoscore on each evaluation. For more information contact Dr Raheela Ashfaq at Veripath OncoDiagnostics at 214.645.7053 or Raheela.Ashfaq@UTSouthwestern.edu.
Selected references:
1. Heimann R et al. Separating favorable from unfavorable prognostic markers in breast cancer: the role of E-cadherin. Cancer Res 60:298; 2000.
2. Ikeguchi M et al. Reduced E-cadherin expression and enlargement of cancer nuclei strongly correlate with hematologic metastasis in colorectal adenocarcinoma. Scand J Gastroenterol 35:839; 2000
3. Mayer B et al. E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res 53:1690; 1993
4. Popov Z et al. Low E-cadherin expression in bladder cancer at the transcriptional and protein provides prognostic information. Br J Cancer 83:209; 2000
5. Umbas R et al. Decreased E-cadherin expression is associated with poor prognosis in patients with prostate cancer. Cancer Res 54:3929; 1994
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