Breast Cancer Tumor Marker Profile: A Comparison of Clinical Laboratory Testing Methods
EK Drinka, N Wadhwani, A Bargaje, C Ersahin, A Salhadar, J Sinacose, P Rajan. Loyola University Medical Center, Chicago, IL
Background: Both morphology and molecular based techniques have been used to measure tumor markers in invasive breast cancer. Immuno-histochemistry (IHC) is currently the standard method to measure estrogen (ER) and progesterone (PR) receptors. There has been excellent correlation between gene copy number of HER-2/neu determined by fluorescence in situ hybridization (FISH) and protein expression by IHC. The high sensitivity and specificity of molecular biology based tests (RT-PCR) offer great potential to individualize treatment and further fulfill the promise of personalized medicine. In this analysis, we compare the sensitivity and specificity of different testing methods for ER, PR and HER-2/neu and we correlate the findings of IHC and FISH tests with RT-PCR results.
Design: We collected 39 invasive breast cancer samples for which tumor marker status (ER, PR and HER-2/neu) was available by 2 or 3 different testing methods: IHC and RT-PCR for ER and PR and IHC, FISH and RT-PCR for HER-2/neu. We calculated sensitivity and specificity for IHC and FISH tests correlating RT-PCR as the gold standard. RT-PCR data was collected from OncotypeDx report (Genomic Health Inc). Student's t test was used to correlate the results by different testing methods.
Results: In our laboratory, both the sensitivity and specificity of test results by IHC and FISH for ER and HER-2/neu were 100% taking RT-PCR as the gold standard .There was also 100% correlation for ER and HER-2/neu when compared with RT-PCR results . There were three false positive cases for PR expression again taking RT-PCR as the gold standard with a sensitivity of 92% and a specificity of 100%. It is important to note that all three false positive PR tumor samples showed low level PR expression (Allred score of 4, 4 and 6). There is a statistically significant relation between low level PR expression by IHC and negative RT-PCR results for PR (p<0.001) in this analysis.
Conclusions: There is complete correlation between ER and HER-2/neu expression by different testing methods (IHC and RT-PCR for ER and IHC, FISH and RT-PCR for HER-2/neu) with 100% sensitivity and specificity. There were 3 false positive PR expression by IHC with a sensitivity of 92% and a specificity of 100%. We found that low level weak PR expression by IHC is correlated with negative PR results by RT-PCR (p<0.001). In conclusion, in selected cases RT-PCR can be used to confirm the tumor marker expression to plan targeted therapy.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 15, Monday Morning