Abstract:
Objectives: Claudin low breast cancers are often high grade, triple negative tumours with poor
prognosis. They are identified at genetic level and are not diagnosed routinely by
immunohistochemistry. The objective was to determine the best subcellular level to detect Claudin
low breast cancer by immunohistochemistry, in terms of their histopathological prognostic
features.
Methods: This cross sectional study included all archival breast cancer tissue collected up to
December 2015 in our unit. Tissue microarrays (TMA) were constructed using 23 breast cancer
cores with a diameter of 2mm, in each TMA. TMAs were immunohistochemically stained for
Claudin 3 expression and was scored as; no staining=0, weak staining=1, moderate staining=2 and
strong staining=3, separately for membrane, cytoplasmic and nuclear staining. A score <2 was
considered Claudin low and analysed against the histopathological prognostic features of the breast
cancer.
Results: A total of 546 breast cancers were assessed. Claudin low expression was identified at
cytoplasmic, membrane and nuclear level in 74.9%, 74.5% and 42% of breast cancers respectively.
Low nuclear expression of Claudin 3 was associated with high grade (p=0.028), Nottingham
Prognostic Index of >3.4 (p=0.028), ER and PR negative (p<0.001) and HER 2 negative (p=0.013)
tumours while low membrane staining was associated with low grade (p=0.038), HER 2 negative
(p<0.001) breast cancers. Low cytoplasmic staining was associated with HER 2 negative breast
cancer only (p=0.002).
Conclusions: Nuclear staining for Claudin should be assessed to identify Claudin low breast
cancer by immunohistochemistry as it significantly associates with most of the Claudin low breast
cancer characteristics.
