[179] HER2 Expression in DCIS Is Highly Associated with DCIS Associated Lymphocytes

Joseph Hatem, Rebecca Batiste, Kathreen Lee, Brian Czerniecki, Paul Zhang. University of Pennsylvania, Philadelphia, PA

Background: HER2 expression is known to be higher in DCIS than invasive ductal carcinoma. Though not considered as a major therapeutic target in DCIS yet, the role of immunotherapy targeting HER2 has currently been explored in DCIS in clinical trials. The histologic characteristics of HER2+ DCIS, particularly those related to the host immunoresponse such as DCIS associated lymphocytes (DAL) have not been well analyzed.
Design: Representative H&E sections of 80 consecutive DCIS from 2011-2012 at our institution were reviewed for histologic type and nuclear grade. DAL was semi-quantitatively analyzed as peri-DCIS lymphoid aggregate (PDLA) with or without direct contact of DCIS (LDCD). Peri-DCIS stromal change (PDSC) was also evaluated. These histologic features were correlated to the results of HercepTest (Dako) performed at the time of the diagnosis in each case.
Results: HER2 was 3+ in 32 (40%) and 2+ in 5 (6%) of all cases. There were 41 (51%) cribriform (HER2 3+ in 9 [22%]), 11 (14%) solid (HER2 3+ in 5 [45%]), 21 (26%) comedo (HER2 3+ in 16 [76%]), 5 (6%) papillary/micropapillary (no HER2 3+) and 2 (2.5%) and Paget (HER2 3+ in 2 [100%]). Table 1 for HER2 results for nuclear grade, PDLA, LDCD, and PDSC.

Table 1
 NGPDLALDCDPDSC
 Low / Int / High<5% / 5-20% / >20%Yes / Focal / NoYes / No
All cases n=8010 / 38 / 3212 / 21 / 3413 / 7 / 6056 / 24
HER2 3+ n0(0%) / 10(26%) / 21(65%)2(8%) / 3(14%) / 27(79%)12(92%) / 3(42%) / 17(28%)28(50%) / 4(17%)
HG DCIS n=32 4 / 8 / 209 / 2 / 21 
HER2 3+ n 1(25%) / 2(25%) / 18(90%)9(100%) / 1(50%) / 11(52%) 



Conclusions: In addition to high grade (65%) and comedo morphology (76%), HER2 is highly expressed in DCIS with prominent PDLA (>20%) (79% vs. 8%) and presence of LDCD (92% vs. 28%) and PDCS (50% vs. 17%). The impact of PDLA and LDCD does not seem to depend upon nuclear grade as it remains strong when only high grade DCIS were analyzed. Since HER2 protein is known to be able to stimulate and activate host immunocytes in vitro, the high incidence of prominent PDLA and LDCD in HER2+ DCIS suggests that the abnormally high HER2 expression could naturally function as a tumor antigen to induce host immunoresponse in these patients. Although the significance is yet to be determined, the assessment of PDLA and LDCD might provide insight to host anti-tumor immunoresponse for predicting and monitoring therapeutic response.
Category: Breast

Monday, March 4, 2013 1:00 PM

Poster Session II # 56, Monday Afternoon

 

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