[107] Her2/Neu (HER2) Intratumoral Genetic Heterogeneity in Breast Cancer and Its Concurrent Axillary Metastases

Kristine Astvatsaturyan, Shikha Bose. Cedars-Sinai Medical Center, Los Angeles, CA

Background: Per the recent guidelines of the College of American Pathologists breast carcinomas are defined as being genetically heterogeneous for HER2 when 5-50% of neoplastic cells demonstrate HER2 amplification. We have previously observed HER2 intratumoral GH in 26% of breast carcinomas. The significance of this finding is unclear at present although it is postulated that this may result in refractoriness to therapy in HER2 negative cancers. Knowledge of the HER2 status in concurrent axillary metastasis from breast cancers with HER2 GH may thus be beneficial in determining therapy. This study is therefore designed to evaluate HER2 GH in paired samples of primary breast carcinoma and its concurrent axillary lymph node (LN) metastases.
Design: 42 cases of infiltrating breast carcinoma with axillary LN metastases (28 cases with GH, 9 cases without GH and 5 cases with HER2 amplification) were retrieved from our files. HER2 GH was evaluated using Ventana Medical Systems' two color chromogenic in situ hybridization in formalin-fixed, paraffin-embedded sections per the manufacturer's guidelines. The HER2 gene was visualized as discrete black signals and Chromosome17 as red signals by light microscopy. The ratio of HER2 gene to Chromosome 17 was calculated for each neoplastic cell in each primary carcinoma and its LN metastases to determine the presence of GH. Breast carcinomas with GH demonstrated HER2 amplification in 5-44% of neoplastic cells present as single scattered cells in 25 cases and as small clusters of amplified cells in 3 cases.
Results:

Comparison of GH in primary breast carcinoma and its axillary metastasis
HER2 in primary carcinomaNo. of casesHER2 in axillary lymph node metastases
  HER2- GH-HER2- GH+HER2+
HER2- GH-9810
HER2- GH+281252
HER2+5005
+ positive; - negative

GH was present in the LN metastasis of 89% (25 cases) of the breast carcinomas with GH. Of these 25 cases, 3 showed a >2 fold increase in GH whereas 3 demonstrated a >2 fold decrease in GH in the metastasis as compared to the primary. HER2 was amplified in the lymph node metastasis in 2 of the 3 cases demonstrating regional HER2 amplification comprising 5 to 15% of the primary carcinoma.
Conclusions: Concurrent axillary metastases from HER2 genetically heterogeneous breast carcinomas:
1) demonstrate variable genetic heterogeneity in the majority of cases.
2) are HER2 amplified in a minority, particularly in those with small areas of HER2 amplification in the primary carcinoma. Such patients may benefit from the evaluation of lymph node metastases prior to the instigation of therapy.
Category: Breast

Tuesday, March 5, 2013 1:00 PM

Poster Session IV # 43, Tuesday Afternoon

 

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