Identification of an Effective Immunohistochemical Panel in Distinction of Breast Carcinoma from Lung Adenocarcinoma
Fan Lin, Shaobo Zhu, Hongbing Deng, Haiyan Liu. Geisinger Medical Center, Danville, PA
Background: When working on a tumor of unknown origin, lung adenocarcinoma versus breast carcinoma often presents a diagnostic challenge because of the overlapping morphological features and immunostaining profile. TTF-1, Napsin A and estrogen receptors (ER) are the recommended panel of markers for this workup. However, these three markers are not entirely sensitive and specific for differentiating a lung primary from a breast primary. In this study, we re-evaluate the expression of an extensive panel of biomarkers, including recently described markers GATA3, Trefoil factor 1 (TFF1) and Trefoil factor 3 (TFF3) using a single immunostaining system (Dako).
Design: We immunohistochemically evaluated the expression of 1) epithelial markers (AE1/3, CAM5.2, CK7, CK20, CK17, CK19, CK903, EMA); 2) mucin gene products (MUC1, MUC2, MUC4, MUC5AC, MUC6); 3) tumor suppressor genes and transcription factors (ER, PR, p53, beta-catenin, WT-1, CDX2, pVHL, ERG); and 4) tumor-associated proteins (TTF-1, napsin A, GATA3 [Santa Cruz; sc-268], TFF1 [Epitomics;AC-0045], TFF3 [AC-0103], FOXA1, HepPar1, glypican 3, SALL4, OCT4, PAX2, PAX8, RCC GCDFP-15, mammaglobin, S100P, IMP3, maspin, MOC31, CEA, CA19-9, CA125, CD10, CD15, villin, and P504S) on 146 cases of breast carcinoma (98 ductal carcinomas and 48 lobular carcinomas) and 111 cases of lung adenocarcinoma on tissue microarray sections. The staining intensity was graded as weak or strong. The distribution was recorded as negative (<5% of tumor cells stained), 1+ (5-25%), 2+ (26-50%), 3+ (51-75%), or 4+ (>75%).
Results: The positive staining results from selected antibodies, which demonstrated diagnostic value, are summarized in Table 1. When combining ductal and lobular carcinomas, the positive staining results for GATA3, ER, TFF1 and TFF3 were 95%, 86%, 77%, and 88%, respectively, with a strong and diffuse staining (3+ or 4+) in 131 cases (90%), 90 cases (72%), 79 cases (56%) and 103 cases (72%), respectively.
|Antibody||Lung ADC||Breast ADC||Breast LCA|
|Napsin A||84/109 (77%)||0/98||0/48|
|GATA3||0/111||90/98 (92%)||48/48 (100%)|
|ER||0/111||77/98 (78%)||48/48 (100%)|
|TFF1||5/111 (5%)||68/95 (72%)||41/47 (87%)|
|TFF3||24/111 (22%)||81/96 (84%)||45/48 (94%)|