Diagnostic Utility of PAX8, Napsin A and TTF-1 in Discriminating Metastatic Carcinoma from Primary Adenocarcinoma of the Lung.
Jiqing Ye, Omar Hameed, Jennifer J Findeis-Hosey, Lifang Fan, Faqian Li, Loralee A McMahon, Qi Yang, Hanlin L Wang, Haodong Xu. University of Rochester Medical Center, NY; University of Alabama at Birmingham; Cedars-Sinai Medical Center, Los Angeles
Background: TTF-1 and napsin A have been considered as useful markers for primary lung adenocarcinoma. However, studies have shown that they can also be expressed in extrapulmonary adenocarcinomas and that a small fraction of lung adenocarcinomas do not coexpress these two markers. The aim of this study was to determine if PAX8, TTF-1 and napsin-A can help segregate primary lung adenocarcinoma from metastasis.
Design: Total 102 metastatic carcinomas of the lung (98 resections and 4 biopsies) were retrieved from authors' institutions. The primary sites included breast (13), salivary gland (6), endometrium (5), ovary (7), endocervix (1), kidney (33), thyroid (5), urinary tract (3), prostate (1), liver (8), adrenal gland (2), and testis (3), pancreatobiliary (7), and colon (8). Tissue microarray of 120 lung adenocarcinomas was used for comparison. Immunohistochemistry was perforemd using antibodies against TTF-1, napsin A and PAX8. Nuclear staining for TTF-1 and PAX8 and cytoplasmic staining for napsin A were considered positive. Immunostaining was graded as weak, moderate or strong and the percentage of positive cells was recorded. A p-value of <0.05, as determined by Fisher's exact test, was considered statistically significant.
Results: Nine of 102 (8.8%) metastatic carcinomas (2 endometrial, 3 colonic, 1 prostatic, 1 salivary adenoid cystic and 2 renal cell carcinomas) showed weak to strong TTF-1 nuclear staining in 5% to 60 % of the tumor cells. The frequency of positive TTF-1 immunostaining in metastatic carcinomas was significantly lower than that reported in primary lung adenocaricnoma by our lab in the past (p<0.01). All metastatic carcinomas were negative for napsin A. PAX8 was strongly positive in 44 (43.1%) of 102 metastatic carcinomas (5/5 endometrial, 1/1 endocervical, 4/6 ovarian, 1/3 urothelial, 3/3 papillary thyroid, 1/1 Hurthle cell and 29/33 renal cell carcinomas). All 120 lung adenocarcinomas were negative for PAX8.
Conclusions: A small fraction of metastatic carcinomas to the lung were TTF-1 positive, which can be confused with lung primaries. However, the metastatic carcinomas are typically negative for napsin A and some of the metastatic carcinomas from kidney, thyroid, ovary, endometrium and urothelium show positive staining for PAX8, a marker that is negative in primary lung adenocarcinomas. These findings indicate that combined use of PAX8, TTF-1 and napsin A is reliable to separate a lung primary from a metastasis
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 271, Tuesday Morning