RNA Binding Protein IMP3 Is Helpful in Differentiating Borderline and Malignant Phyllodes Tumor of the Breast
Xiaofang Yang, Berrin Ustun, Steven Goodman, Dina Kandil, Ashraf Khan. UMassMemorial Medical Center, Worcester, MA
Background: Phyllodes tumor (PT) is a rare fibroepithelial neoplasm of the breast, which at times poses a challenge to separate into prognostically reliable categories especially on needle core biopsy (NCB). Several classification schemes have been proposed to grade PT; some using a two-tier scheme into benign and malignant, while others suggest dividing them into three categories: benign, low-grade malignant and high-grade malignant; or benign, borderline, and malignant. The latter grading scheme has been adopted by the WHO and employs histologic criteria such as stromal hypercellularity, pleomorphism, tumor margins and mitotic activity. Ki67 have been found useful in classification of PT but no standard threshold is established and there remains a need for additional biomarkers that may assist in the grading of PT. IMP3, an oncofetal protein, is a member of the insulin-like growth factor-II (IGF-II) mRNA-binding protein family. Its relevance as a biomarker in separating benign and malignant epithelial and mesenchymal tumors have been recently reported and therefore seems to be a good candidate for evaluation in PT.
Design: We retrieved all PTs resected at our institution over a 12-year (1999-2010) period. The slides were reviewed and PT classified according to the WHO criteria into benign, borderline and malignant category. IMP3 immunostaining was performed on all cases and Ki67 immunostaining on all borderline and malignant tumors. IMP3 immunostaining was considered positive if stromal tumor cells showed cytopalsmic and/or membranous staining. Ki67 index was calculated by counting percent of stromal cells showing nuclear immunoreactivity. IMP3 expression was correlated with tumor grade, tumor size and Ki67 index. Statistical analysis was performed using the Student's T-test (2-tailed).
Results: Fifty-one PTs cases on which blocks and slides were available included benign (n=33), borderline (n=13) and malignant (n=5). The median age at resection was 41, 49, and 65 years for benign, borderline, and malignant PTs, respectively. All 33 benign and 13 borderline PTs were IMP3 negative, while all 5 malignant PTs showed varying degrees of IMP3 immunostaining (p= 0.004). Mean Ki67 index was significantly higher (10.6%) in IMP3 positive (malignant) compared to (3.35%) in IMP3 negative (borderline) tumors (p=0.02). There was no correlation between IMP3 expression and tumor size (p=0.43).
Conclusions: IMP3 is preferentially expressed in malignant PT. Immunostaining for IMP3-oncofetal protein can be a helpful tool in classifying PTs in challenging cases, especially in NCB.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 58, Wednesday Morning