The Role of Type XI and Type XVII Collagen in Breast Cancer Progression.
Ana C Vargas, Peter Simpson, Lane Annette, Smart Chanel, Amy Reed, Da Silva Leonard, Lakhani Sunil. UQ Centre for Clinical Research, Brisbane, Australia
Background: The COL11A1 is an extracellular matrix protein with a role in cell adhesion. COL11A1 has been shown to be significantly regulated in colorectal cancer compared to adenomas (Fisher et al, 2001) and recently, it was shown to be highly over-expressed (>100 fold) in primary breast cancer compared to their matched lymph node metastasis (Ellsworth et al, 2009). However, there is no current data about the role of COL11A1 in breast cancer compared to its precursor lesion, Ductal Carcinoma In Situ (DCIS). On the other hand, COL17A1 role in breast carcinogenesis has not been investigated yet.
Design: Sixteen FFPE samples of patients with matched IDC, DCIS and normal breast were retrieved from the archives of the RBWH. Tumour microdissection, RNA extraction and Gene Expression profiling (DASL, Illumina) were performed. Real Time-PCR (RT-PCR) and immunofluorescence (IF) were used for validation in an additional cohort of 20 IDC-DCIS fresh frozen samples.
Results: Gene Expression Profiling showed that two collagen molecules were differentially expressed in IDC compared to DCIS in an inverse reciprocal pattern.
COL17A was expressed in the normal breast with progressive down-regulation in DCIS and IDC. On the other hand, COL11A1 was expressed at low levels in both normal breast and DCIS with significant up-regulation in the invasive compartment. RT-PCR efficiently confirmed the microarray results. IF also showed COL11A1 expression in the cytoplasm of the tumour cells.
Focal positive expression was observed only in the stroma surrounding the tumour (< 3 mm), indicating that close tumour stromal-epithelial interactions are required for its expression. COL17A1 showed negative expression in IDC with weak scatter staining in the normal breast.
Conclusions: We hypothesize that COL11A1 play a role in the IDC-DCIS transition and therefore, local invasion and metastasis. Down-regulation of COL17A1 in breast cancer has not yet been reported but further work is required to confirm this observation.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 21, Tuesday Afternoon