Tubular Breast Carcinoma: Critical Evaluation of ER/PR Expression and Gene Expression Profile.
Julie Jorns, Daniel Visscher, Dafydd Thomas, Patrick Healy, Stephanie Daignault-Newton. University of Michigan, Ann Arbor
Background: Tubular carcinoma (TC) is a rare breast cancer subtype with low lymph node (LN) involvement and favorable overall prognosis. Like other well-differentiated carcinomas, TC is typically estrogen and progesterone receptor (ER/PR) positive. However, there are few studies examining staining intensity, which is often heterogeneous, resembling that of normal breast. Early gene expression profiling has shown that TCs fit in the luminal A (LumA) subgroup, which are low grade, good prognosis tumors with high ER expression. However, a gene expression profile distinguishing TC from other LumA tumors is yet to be described.
Design: Tubular (T) (N=25), Mixed ductal/tubular (M) (N=15), and Ductal (D) (N=27) groups were compared. All were mBR grade 1 and stratified by % of tubular features defined as: open, angulated tubules; cytoplasmic tufting; and low grade cytology with ≥90%, 25-89%, and <25% tubular features for T, M, and D groups, respectively. Tumors were examined by 2 pathologists with expertise in breast pathology. Slides with representative tumor were immunostained for ER/PR and both % staining in tumor and normal glands (within the same slide) were assessed using a quantitative and validated method (VIAS). 12 benign macromastia cases served as positive controls. 10 tumors from each of the T and D groups were evaluated by gene expression profiling using the RT-PCR-based PAM-50 assay. Other clinicopathologic features assessed were age at diagnosis, tumor size and LN status.
Results: Mean age at diagnosis was 58, 57, and 59 yrs and tumor size 0.7, 0.8, and 0.8 cm for T, M, and D groups, respectively. All were LN stage pN0. There was no difference in ER/PR staining in normal glands among groups nor was there a significant relationship between tumor subtype and PR%. TCs had a statistically-significant decreases in tumor ER% (Tukey Kramer adjusted pairwise comparison p=0.003) and difference between tumor and normal ER% (wilcoxin signed-rank test p=0.025) when compared to IDC, with intermediate values in the mixed group; mean ER% were 79%, 87%, and 94% and mean ER differences between tumor and normal were 14.1%, 25.9%, and 32.6% in T, M, and D groups, respectively. 20 tumors sent for PAM-50 revealed 9/10 TC and 8/10 IDC to be LumA, 1 TC and 1 IDC to be normal-breast like, and 1 IDC insufficient for analysis. PAM-50 raw data is currently under analysis.
Conclusions: TCs are LumA breast cancers with exceptional prognosis even amongst this subgroup. Differential ER expression between TC and grade 1 IDC supports pathogenetic distinction.
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 24, Tuesday Afternoon