Abstract

Abstract Background: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are the most important predictive and prognostic biomarkers in breast cancer. The American Society of Clinical Oncology/College of American Pathologists recommends that the time from tumor removal to fixation (cold ischemic time) should be kept within 1 hour. Through this study we mean to review the actual cold ischemic time in real practice and analyze whether delayed formalin fixation effects immunohistochemical (IHC) testing results. Methods: Patients, who received surgery for invasive or in situ breast cancer in Seoul National University Hospital, Seoul, Korea between February and December 2013, were retrospectively reviewed. Cold ischemic time was calculated by extracting the time of formalin fixation from the time when surgery ended. All patients were equally divided into two groups (short ischemic group, long ischemic group) according to median cold ischemic time. Chi-square test was done for ER and PR positive/negative (0% negative, ≥1% positive) and student t-test was done for ER and PR percentage. Also χ2 test was done for HER2 positive/negative and scoring system ranging from 0 to 3+. Results: A total of 615 patients were included in this study. The median cold ischemic time was 2h 43min 4sec (range 6min 36sec – 84h 26min 20sec). Only 48 patients had a cold ischemic time shorter than 1 hour. No association between ER, PR expression and cold ischemic time was found in the χ2 test (p=0.581, p=0.954) and student t-test (p=0.648, p=0.978). As for HER2 expression, in the long ischemic group, there were significantly more patients with positive immunohistochemical testing results (χ2 test, p=0.016), and significantly higher grades in HER2 scoring system (χ2 test, p=0.022). Compared to IHC results, FISH testing for HER2 amplification showed no significant difference (χ2 test, n=145, p=0.500). This tendency was persisted when patients were divided into four groups by 25 quartile of cold ischemic time. Conclusions: Our findings show that the actual cold ischemic time in practice is longer than recommended guidelines. Despite that, ER, PR expression was not associated with cold ischemic time. As for HER2 expression, longer cold ischemic time was associated with more HER2 positive and higher HER2 score. But this tendency was not showed in FISH testing for HER2 amplification. Citation Format: Tae-Kyung Yoo, Hyeong-Gon Moon, Jisun Kim, Jun Woo Lee, Min Kyoon Kim, Eunshin Lee, Jongjin Kim, Wonshik Han, In-Ae Park, Dong-Young Noh. Effect of prolonged cold ischemic time on immunohistochemical testing of estrogen receptor, progesterone receptor and HER2 expression in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-10-10.

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