HER2 Testing in Endometrial Carcinoma: Four-Year Experience at a Large Tertiary Academic Center
Natalia Buza, Diana English, Alessandro D Santin, Pei Hui. Yale University School of Medicine, New Haven, CT
Background: HER2 overexpression and/or amplification have been previously reported in endometrial carcinoma (EC), suggesting that HER2 may be a promising therapeutic target. However, there is considerable variation in the reported rates, likely resulting from variability in testing methods, interpretation, and scoring criteria used. Currently there are no established guidelines for HER2 testing in EC.
Design: All EC cases between 2008 and 2012 with available HER2 status were retrieved from our departmental archives. H&E and immunohistochemical (IHC) slides were reviewed along with HER2 fluorescent in situ hybridization (FISH) images. HER2 IHC slides were systematically evaluated by two gynecologic pathologists and scores were assigned per the original FDA criteria and also per current breast scoring criteria. Clinical data were retrieved from the patients' medical records.
Results: A total of 112 EC - 85 pure serous carcinoma (SC), 23 mixed EC (with SC component) and 4 endometrioid EC - were included in the study. Thirty-eight cases (33.9%) were positive by HER2 IHC (3+) and/or FISH, 17 of which (44.7%) showed significant heterogeneity in IHC staining intensity. Significant IHC heterogeneity was also observed in 11 of 74 cases (14.8%) in the HER2 negative group. The % of cells with strong, complete membrane staining in cases with heterogeneity ranged between 5% and 80%. Incomplete, “U-shaped” staining pattern was frequently encountered (at least focally) in both the HER2 positive and negative groups. Five of the HER2 positive cases (13.1%) showed discrepant IHC scores when using the FDA versus the current breast scoring criteria. Discordant results between IHC and FISH were observed in 6 of 112 cases (5.3%).
Conclusions: This is the largest comprehensive study to date systematically evaluating HER2 overexpression and amplification in EC, using standardized scoring criteria. Overall, 33.9% of cases showed HER2 overexpression and/or amplification. Unlike in breast cancer, heterogeneous and incomplete (“U-shaped”) HER2 expression occurs frequently in EC, potentially resulting in discrepant IHC scores. Our results underline the need for EC-specific HER2 scoring guidelines to reflect the unique biological features of these tumors. A clinical trial is currently underway evaluating trastuzumab in patients with HER2 positive SC, and ultimately the correlation of clinical response with HER2 results will help to standardize HER2 testing and scoring in EC.
Category: Gynecologic & Obstetrics
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 124, Tuesday Morning