Lobular Carcinoma Progression Model: Immunohistochemical Analysis on Tissue Microarray
F Chen, J Cangiarella, L Chiriboga, F Darvishian. NYU-Langone Medical Center, New York, NY
Background: Lobular carcinoma in situ (LCIS) is generally considered a marker for higher risk. However, there is evidence to show the progression of LCIS to invasive lobular carcinoma (ILC) as the two share some similar genomic alterations including chromosome 16q loss and 1q gain. In this pilot study, our objective was to seek the role of several carcinogenic markers in the evolution and progression of the lobular carcinoma of the breast.
Design: We generated a tissue microarray (TMA) including cores from normal lobules, LCIS and ILC in each case. Immunohistochemical (IHC) antibodies for E-cadherin, β-catenin, IGF1, IGF2, EGFR, ER, PR, her2, BRCA1, BRCA2, MLH1, MSH2, p53, bcl-2 and cyclin D1 were applied to the sections made from the TMA paraffin blocks. We scored each of the three components (i.e. normal lobule, LCIS, ILC) in every core separately by adding the score for distribution (0-4) to the score for intensity (0-3) with a maximum score of 7. Scoring of her2 was performed according to the Dako scoring system.
Results: We randomly identified 39 cases diagnosed as ILC (mean age: 62.4 years). In all cases, the LCIS and ILC were completely negative for E-cadherin. Membranous β-catenin staining was observed in 79% of normal lobules, 12.8% of LCIS and 20.5% of ILCs. Cytoplasmic (Golgi pattern) β-catenin staining was observed in 0% of normal lobules, 18% of LCIS and 38% of ILCs. See table 1 for IHC analysis.
|Normal Lobules (mean)||LCIS (mean)||ILC (mean)|
|21 (53%)||18 (47%)|
|Subtype||Classical ILC||Pleomorphic ILC|
|34 (87%)||5 (13%)|
|20 (51%)||16 (41%)||3 (8%)|
|21 (53%)||12 (31%)||3 (8%)||3 (8%)|
|8 (20%)||31 (80%)|