Molecular phenotyping and tissue microarray (TMA) studies have identified distinct invasive
breast carcinoma subtypes:
Luminal A,
luminal B, enriched with overexpressed
human epidermal growth factor receptor 2 (HER-2) and triple-negative, i.e., negative for HER-2, as well as for
estrogen and
progesterone receptor (ER and PR, respectively) expression. These subtypes are useful in clinical management, since they bear distinct prognoses and predictive responses to targeted
therapy. However, although molecular profiling provides important prognostic indicators,
breast cancer risk stratification remains a challenge in triple-negative cases. What is referred to as
claudin-low subtype was identified as a triple-negative subset that is associated with more aggressive
tumor behavior and worse prognosis. However, the immunohistochemical expression of
claudins has not yet been standardized. Our objective was to verify whether the immunoexpression of
claudins 4 and 7 (the main
claudins specifically expressed in human breast tissue) in TMA is associated with survival and prognosis in
luminal A, HER-2 and triple-negative molecular subtypes. In this diagnostic study, we investigated ER/PR receptor status, HER-2,
claudin 4 and 7 expression and stem cell CD44/24 profiles, and verified the association with prognosis and survival outcomes in 803 invasive
breast carcinoma cases arranged in four TMAs. Among these, 503 (62.6%) were positive for
claudin 4 and 369 (46.0%) for
claudin 7.
Claudin 4 exhibited the lowest expression in
luminal A and triple-negative subtypes, and the highest frequency of expression in HER-2-enriched subtypes, whereas
claudin 7 staining was not associated with any subtype. The stem cell phenotype was not associated with subgroups or
claudins 4 and 7.
Claudin immunoexpression profile was not able to distinguish between patients with better or worse prognosis, and it was not correlated to triple-negative cases. Therefore, it may be concluded that the immunoexpression of
claudins 4 and 7, individually or within the usual immunohistochemical context (ER, PR and HER-2), does not provide additional prognostic information on
breast cancer subtypes.