LYRIC Is Associated with an Increased Incidence of Distant Metastasis and Loco-Regional Recurrence in Patients with Breast Carcinoma
Joseph P Bergeron, Hope T Richard, Justin Richey, Jorge A Almenara, Michael O Idowu. Virginia Commonwealth University, Richmond, VA
Background: Overexpression of LYRIC, also known as astrocyte elevated gene-1 (AEG-1)/metadherin, has been reported to be associated with breast cancer progression. However, limited information is available on the association of LYRIC overexpression and distant metastatic or recurrent disease in breast carcinomas. Elucidation of pathways that lead to tumor progression and metastases is vital for the development of targeted therapy. This study evaluated the relationship between LYRIC expression and loco-regional recurrence, distant metastasis, axillary lymph node status, histologic grade, and triple negative tumors.
Design: The clinical outcome and pathologic characteristics of breast carcinoma cases from 1992 to 2008 with adequate follow-up information were reviewed. A minimum of 60 months of follow-up was required for inclusion of cases without recurrence or metastases. For each case, tissue microarrays (TMA) were created by obtaining 1 mm cores in triplicate from different areas of the tumor using an automated TMA system (Beecher ATA-27). The specimens were stained with a rabbit polyclonal antibody to LYRIC (Abcam, Ma USA). The cases were reviewed independently by two pathologists. Cases with moderate to intense cytoplasmic and nuclear staining were considered positive. Statistical significance was determined using a Chi-squared test.
Results: Of 285 cases, 86 were found to have distant metastases and 34 had loco-regional recurrence. The median follow-up period for all cases was 72 months, and ranged from 12 to 228 months. A greater proportion of cases with distant metastases and cases with local recurrence were associated with LYRIC positivity (59 vs 27, p= 0.006) and (26 vs 8, p= 0.004), respectively. Additionally, LYRIC positivity was associated with axillary lymph node metastasis (92 vs 26, p=0.004), high histologic grade (74 vs 37, p=0.003) and triple negative hormone receptor status (48 vs 27, p=0.003).
|LYRIC pos||LYRIC neg|
|% distant mets (n=86)||69% (59)||31% (27)|
|% local recur (n=34)||76% (26)||24% (8)|
|% grade III (n=111)||67% (74)||33% (37)|
|% high Ki67 (n=95)||69% (66)||31% (29)|
|triple neg (n=75)||64% (48)||36% (27)|
|% LN pos (n=118)||78% (92)||22% (26)|