Survivin expression in in situ and invasive breast cancer relates to COX-2 expression and DCIS recurrence

N. Barnes, P. Haywood, P. Flint, W. F. Knox, N. J. Bundred

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    In lung cancer cyclooxygenase-2 (COX-2) expression has been reported to stabilise survivin, an inhibitor of apoptosis (IAP) which prevents cell death by blocking activated caspases. COX-2 expression limits the ubiquitination of survivin, protecting it from degradation. To determine if COX-2 expression in breast cancer showed an association with survivin expression, we assessed the levels of each protein in ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC); relating expression patterns to recurrence of DCIS after surgery. Patterns of COX-2 and survivin expression were determined by intensity-graded immunohistochemistry of the primary tumours. Patients with DCIS (n = 161) which had either recurred (n = 47) or shown no evidence of recurrence (n = 114) 5 years following primary surgery were studied. These were compared to 58 cases of IBC. Survivin was expressed in the cytoplasm of 59% of DCIS and 17% of IBC. High levels of both cytoplasmic survivin and COX-2 expression significantly correlated to DCIS recurrence. COX-2 expression was present in 72% of DCIS, and levels of expression positively correlated with cytoplasmic survivin expression in DCIS and invasive disease. The majority of DCIS that recurred expressed both proteins (69%) vs 39% nonrecurrent. Recurrence was not seen in DCIS lacking both proteins at 5 years (P = 0.001). Expression of the IAP survivin is increased in DCIS and correlates closely with COX-2 expression. Increased expression of IAP, (leading to reduced apoptosis) may explain the effect of COX-2 in increasing recurrence of DCIS after surgical treatment. © 2006 Cancer Research.
    Original languageEnglish
    Pages (from-to)253-258
    Number of pages5
    JournalBritish Journal of Cancer
    Issue number2
    Publication statusPublished - 30 Jan 2006


    • Apoptosis
    • Breast
    • Cyclooxygenase
    • DCIS
    • Recurrence
    • Survivin


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