Calreticulin Expression in Breast Cancer: Correlation with Prognostic Factors.
Summer L Bohman, Cynthia Cohen, Gabriela Oprea, Harold C Sullivan, Blazej Zbytek, Amy Adams. Emory University, Atlanta, GA
Background: Calreticulin, an endoplasmic reticulum protein that aids in maintaining intracellular calcium and in protein folding, plays an important role in autoimmunity and has an association with certain types of cancer. Recently, its role in the pathogenesis of breast carcinoma and as a marker of aggressive behavior has been suggested. Our goal is to correlate calreticulin expression in breast carcinoma with tumor subclass (estrogen receptor [ER]-positive vs ER/progesterone receptor/HER2-neu "triple" negative) and other clinicopathologic features.
Design: Invasive breast carcinomas from two patient groups, one ER-positive and the other triple negative (TN), were identified. Tissue microarrays (TMA) were created from representative tissue blocks, and an immunoperoxidase stain for calreticulin (Upstate) was performed on TMA sections. The cytoplasmic positivity was scored using an intensity score derived by multiplying the staining intensity (0-3) by the percentage of tumor cells immunopositive. Staining was designated as negative/weak (scores ≤ 100) and moderate/strong (scores >100). Calreticulin expression was compared to features including tumor subclass, race, tumor size, grade, lymph node status, angiolymphatic invasion, and Oncotype DX (Genomic Health) recurrence score.
Results: We identified 248 patients, 27 (10.9%) with no or weak calreticulin expression, and 221 (89.1%) with moderate to strong staining. TN (n=123) and ER-positive patients (n=125) showed no difference in frequency of calreticulin expression (p=0.7184). There was a trend for association of calreticulin expression with higher tumor grade (Table 1). Calreticulin expression showed no correlation with race, tumor size, lymph node status, or angiolymphatic invasion. For the ER-positive subset, there was no correlation with Oncotype DX recurrence score.
|Grade I||Grade II||Grade III||P Value|
|Calreticulin No/Weak||4 (1.6%)||16 (6.5%)||7 (2.8%)|
|Calreticulin Moderate/Strong||33 (13.4%)||82 (33.3%)||104 (42.3%)||0.0689|