Molecular Characterization of DCIS by Immunohistochemistry: Correlation with Histologic Grade, Ki-67, Bcl-2 and p53 Expression
JS Han, R Ashfaq, Y Peng, VR Sarode. University of Texas Southwestern Medical Center at Dallas, Dallas, TX
Background: DCIS is a heterogenous disease with a wide spectrum of morphologic types. Recently, gene expression studies on invasive carcinoma have revealed molecular subtypes. Immunohistochemical analysis using ER, PR and Her2Neu as a surrogate for gene expression, invasive carcinomas have been classified into four major subtypes: luminal A (ER+, PR+, Her2-); luminal B (ER+, PR+, Her2+); Her2 + and triple negative (ER-, PR- and Her2-) . The aim of this study is to characterize DCIS into distinct molecular subtypes by immunohistochemical stains for ER, PR and Her2Neu. To determine if there is a correlation of the different groups of DCIS with histologic grade, ki-67, Bcl-2 and p53 expression.
Design: A total of 118 patients with a diagnosis of pure DCIS were retrieved from the archives of the Department of Pathology at UTSW Medical Center, from January 2000 to August 2007. Clinical and pathologic data such as patient's age, histologic grade and results of immunohistochemical studies for ER, PR, Her2Neu, ki67, bcl2 and p53 were retrospectively analyzed. Histologic grading of DCIS was performed according to CAP guidelines. DCIS was stratified into four groups: (ER+, PR+ and Her2-); (ER+, PR+ and Her2+); (ER-, PR-, Her2+) and (ER-, PR- and Her2-). Each of the four groups of DCIS was correlated with histologic grade, Ki-67, Bcl2 and p53 expression. Statistical analysis was performed by one-way ANOVA with post hoc test.
Correlation of DCIS with age, nuclear grade, Ki-67, Bcl-2 and p53 is shown below: (mean SEM)
|DCIS subtypes Total =118||ER+PRHer2- 75 (63.6%)||ER+PRHer2+ 22 (18.6%)||ER-PR-Her2+ 14 (11.9%)||ER-PR-Her2- 7 (6.0%)||P Value|
|Intermediate grade DCIS||50%||20.8%||14.3%||21.2%|
|High grade DCIS||30.9%||62.5%||85.7%||78.8%||0.002|
Conclusions: Low and intermediate grade DCIS were predominantly of the luminal A and B types. Both were associated with high Bcl-2 expression, low proliferation and low p53. Triple negative and Her2Neu subtypes were significantly associated with high grade DCIS, increased p53 expression, high proliferation and low Bcl-2.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 41, Tuesday Morning