An Oncofetal Protein IMP3, a New Molecular Marker for the Detection of Dysplasia and Carcinoma of the Gallbladder.
Thomas Stockl, Zhong Jiang. UMass Memorial Medical Center, Worcester, MA
Background: Gallbladder adenocarcinoma is a very aggressive cancer with a 13% 5-year survival rate. Clinically, it is crucial to recognize epithelial dysplasia, a premalignant lesion in the gallbladder. However, distinguishing dysplasia from reactive atypia in cholecystectomy specimens often presents a diagnostic challenge to pathologists. A reliable biomarker that can unambiguously identify dysplasia from reactive changes will be very useful for histological diagnosis of dysplasia and adenocarcinoma. IMP3, an oncofetal protein, plays an important role in carcinogenesis in different cancers. Several studies have shown that IMP3 is a cancer specific biomarker. The aim of this study was to establish the expression pattern and diagnostic value of IMP3 in dysplasia and carcinoma of the gallbladder.
Design: A total of 95 cases (cholecystectomy specimens) with 139 lesions (invasive adenocarcinoma, n=25; high grade dysplasia, n=8; low grade dysplasia, n=26; benign gallbladder, n=80) obtained from the surgical pathology files of a tertiary Medical Center were examined by immunohistochemistry for IMP3 expression. ≥5% of epithelial/tumor cells stained with IMP3 antibody was considered as positive staining. Focal staining was defined as IMP3 positivity in 5-50% and diffuse staining as IMP3 positivity in >50% of lesional epithelia/glands.
Results: IMP3 showed dark brown cytoplasmic staining. IMP3 expression was found in 24/25 (96%) of invasive carcinomas, 8/8 (100%) of high grade dysplasia, and 23/26 (88%) of low grade dysplasia. Diffuse IMP3 positivity was found in 18/25 (72%) of cases with invasive carcinoma, 6/8 (75%) of cases with high-grade dysplasia and 9/26 (35%) of cases with low grade dysplasia. In contrast, all benign gallbladder (n=45) and benign epithelia adjacent to the cancer or dysplasia (n=35) were negative for IMP3 staining.
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