Co-Expression of p16 and p53 in the Spectrum of Ductal Intraepithelial Neoplasias.
Charles J Bechert, J Y Kim, Fattaneh A Tavassoli. Yale University, New Haven, CT
Background: Ductal intraepithelial neoplasias 1-3 (DCIS, grades 1-3) develop recurrences in 10-20% of the cases, about 50% of which are invasive. Currently, most women with DIN1-3 are treated by lumpectomy followed by radiation therapy with or without hormonal therapy. A better understanding of the true nature of each patient's DIN lesion would result in a more personalized therapeutic approach and ultimately improved clinical outcomes. Prior studies have shown that invasive breast carcinomas positive for p16 or p53 have a higher frequency of recurrence and a more aggressive course. The co-expression of these markers in the entire spectrum of DIN and its potential correlation with the grade of the lesions has not been evaluated in the past.
Design: Immunostains for p16 and p53 were evaluated on 297 DIN lesions from cases diagnosed between 1991 and 2008 at Yale New Haven Hospital. The lesions ranged from low-risk DIN (IDH) to DIN3 and included some with invasive carcinoma. The cases were reviewed separately by 2 pathologists, and blocks were selected for immunohistochemical staining along with positive and negative controls. The intensity of nuclear staining for p53 was scored from 0 to 4; cases were considered positive if there was at least (2+) intensity in at least 10% of the cells. Immunoreaction for p16 (nuclear and cytoplasmic) was considered positive if at least 25% of the cells were positive.
Results: The lesions consisted of 37 LRDIN (IDH), 67 flat DIN1 (FEA), 25 DIN1 ≤ 2mm (AIDH), 46 DIN1 > 2mm (DCIS grade-1), 86 DIN2, and 36 DIN3. Co-expression of p16 and p53 was noted in 13%, 12%, 21%, 24%, 32% and 64% of each DIN category respectively. The frequency of positivity for both p16 and p53 increased with increasing grade of DIN. Furthermore, double positivity (p16+/p53+) was noted in 77% of DIN3 lesions associated with invasive carcinoma.
Conclusions: Co-expression of p16 and p53 increases with advancing grade of DIN and is maximally expressed among high grade DIN lesions associated with invasive carcinoma. This information could be used to identify or predict DIN lesions prone to invasion and potentially also to recurrence and would significantly impact management and therapies offered to patients with DIN.
Monday, February 28, 2011 1:00 PM
Poster Session II # 44, Monday Afternoon