Expression of E-Cadherin and -Catenin in Gastro-Intestinal Neuroendocrine Tumours
R Jain, S Serra, R Chetty. University Health Network/University of Toronto, Toronto, Canada
Background: -catenin is a multifunctional molecule that acts as transcription factor resulting in cell proliferation and differentiation in the Wnt pathway. It interacts with E-cadherin, a transmembrane adhesion molecule.
Design: To examine the expression of -catenin and E-cadherin in gastrointestinal neuroendocrine tumours (GI NETs). Nineteen cases were retrieved from the archives of the department of Pathology, UHN and stained with a -catenin and two antibodies (Abs) (against extracellular (ECD) and cytoplasmic domains(CD)) to E-cadherin. Parameters examined were localization (membrane vs cytoplasm); intensity, 0 (negative), 1+ (weak), 2+ (moderate), 3+ (strong); percentage positive cells, <5% (0), 5-30% (1+), >30-70% (2+), > 70% (3+). An index of staining was calculated (intensity by % positive cells).
Results: Age range: 36-93 years, 14 were males. E-cadherin immunoreactivity with the Ab against the CD was cytoplasmic in all cases, being weak to moderate in more than 80% of the cases. Nuclear positivity was seen in 3/19 cases, while membranous immunoreactivity was seen in 10. E-cadherin immunoreactivity with Ab against the ECD was cytoplasmic in 18/19 cases and also membranous in 12, without any nuclear staining. One case was negative. Membranous staining was seen in more than 50% cells in 9/10 cases with CD Ab and 9/12 cases with ECD one. There was not significant difference in intensity of immunoreactivity between the two Abs. There was a progressive loss of membranous immunoreactivity from T1 to T4 tumors, while cytoplasmic staining was seen in all the cases irrespective of the stage. No correlation was seen between nuclear staining and stage. TNM staging was not possible in two cases. Dot like E-cadherin cytoplasmic positivity was seen in more advanced tumors (T2-T4 and N1), with both the Abs. -catenin immunoreactivity was cytoplasmic in 5/19 cases, cytoplasmic and nuclear in 5, cytoplasmic and membranous in 1, nuclear and membranous in 1, and 7/19 cases showed only membrane immunoreactivity. 10/11 tumors showed cytoplasmic or nuclear positivity in more than 30% cells, whereas membrane positivity was from weak to moderate. There was a progressive loss of membranous staining and increase of nuclear/cytoplasmic staining from T1 to T4 tumors.
Conclusions: GI NETs show dysregulation in Wnt pathway with aberration in E-cadherin and -catenin: progressive loss of membranous immunoreactivity with all the three Abs with increasing stage of the tumors. The two Abs against E-cadherin show a similar pattern of staining.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 90, Tuesday Afternoon