Expression of COX-2, p16, and p53 in Ductal Intraepithelial Neoplasia
JY Kim, S Sanati, FA Tavassoli. School of Medicine, Pusan National University, Busan, Korea; Yale University School of Medicine, New Haven, CT
Background: Breast cancer is a heterogeneous disease with multiple genetic pathways influencing tumor growth and progression. Identification of markers overexpressed during carcinogensis can have diagnostic and therapeutic implications. Recent studies have implicated COX-2 expression as an early marker in breast carcinogenesis, while p16 overexpression, an inhibitor of cyclin-dependent kinases 4 and 6, has been noted in a variety of cancers including hormone dependent tissues. p53 tumor suppressor gene plays an important role in the regulation of the apoptotic response of cells following exposure to stress. To determine the role of these alterations in mammary carcinogenesis, a series of breast lesions ranging from low-risk ductal intraductal neoplasia (L-R DIN, intraductal hyperplasia) to invasive carcinoma were evaluated with immunostains for COX-2, p16 and p53.
Design: Eighty cases were retrieved from the surgical pathology files of our institution. These included 20 L-R DIN, 25 flat DIN 1 (flat epithelial atypia), 13 DIN 1, 2 mm (atypical ductal hyperplasia), 10 DIN 1, > 2 mm (DCIS, grade 1), 32 DIN 2 (DCIS, grade 2), and 17 DIN 3 (DCIS, grade 3). Thirty cases co-existed with invasive carcinoma. Immunohistochemical stains for COX-2, p16, and p53 were performed according to manufacturer's guidelines. Immunostains were graded based on intensity and percentage of positive cells and were reviewed by 3 pathologists.
Results: COX-2 had maximum expression in normal mammary tissue, L-R DIN and flat DIN 1. The maximum p16 expression was noted in DIN 3 and DIN 1, 2mm. p53 had a gradual increase in expression from normal mammary epithelium to DIN3. The results are summarized in table 1.
Cox-2, p16 and p53 expression in DIN lesionsTable 1
|Marker||Normal, N=71||L-R DIN, N=20||Flat DIN1, N=20||DIN1, 2mm, N=13||DIN1 (DCIS, grade 1), N=10||DIN2 (DCIS, grade 2), N=36||DIN3 (DCIS, grade 3), N=17|
Conclusions: Our data suggests an inverse relationship between COX-2 expression on one hand and p16 and p53 expression on the other hand in a range of breast lesions, with a higher rate of COX-2 over-expression in early lesions and increased p16 and p53 expression in more advanced lesions. Particularly notable was the heterogeneity of expression among cases of a specific subtype as well within a given case.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 33, Tuesday Morning