Kaiso is highly expressed in TNBC tissues of women of African ancestry compared to Caucasian women

Abstract

Purpose: Triple-negative breast cancer (TNBC) is most prevalent in young women of African ancestry (WAA) compared to women of other ethnicities. Recent studies found a correlation between high expression of the transcription factor Kaiso, TNBC aggressiveness, and ethnicity. However, little is known about Kaiso expression and localization patterns in TNBC tissues of WAA. Herein, we analyze Kaiso expression patterns in TNBC tissues of African (Nigerian), Caribbean (Barbados), African American (AA), and Caucasian American (CA) women.

Methods: Formalin-fixed and paraffin embedded (FFPE) TNBC tissue blocks from Nigeria and Barbados were utilized to construct a Nigerian/Barbadian tissue microarray (NB-TMA). This NB-TMA and a commercially available TMA comprising AA and CA TNBC tissues (AA-CA-YTMA) were subjected to immunohistochemistry to assess Kaiso expression and subcellular localization patterns, and correlate Kaiso expression with TNBC clinical features.

Results: Nigerian and Barbadian women in our study were diagnosed with TNBC at a younger age than AA and CA women. Nuclear and cytoplasmic Kaiso expression was observed in all tissues analyzed. Analysis of Kaiso expression in the NB-TMA and AA-CA-YTMA revealed that nuclear Kaiso H scores were significantly higher in Nigerian, Barbadian, and AA women compared with CA women. However, there was no statistically significant difference in nuclear Kaiso expression between Nigerian versus Barbadian women, or Barbadian versus AA women.

Conclusions: High levels of nuclear Kaiso expression were detected in patients with a higher degree of African heritage compared to their Caucasian counterparts, suggesting a role for Kaiso in TNBC racial disparity.

Keywords: Breast cancer racial disparity; Kaiso; TNBC; Women of African ancestry.

Fig. 1

Nigerian women are diagnosed with TNBC at younger ages than Barbadian, AA, and CA women. a The mean age at diagnosis for Nigerian TNBC patients was 42.6 years (n = 25) compared with 52.1 years for Barbadian women (n = 46), 51.5 years for AA women (n = 13), and 56.2 years for CA women (n = 37). No significant differences were observed between the mean age at diagnosis for Barbadian versus AA and CA TNBC patients (b) and for AA versus CA patients (c). ^* p < 0.05, ^** p < 0.005, ^**** p < 0.0001

Fig. 2

Cytokeratin immunostaining of Nigerian and Barbadian TNBC tissues verifies tissue integrity. IHC images at low (5×) and high magnification (40×) show intact tissue cores (a, b) and membrane localization (ai, bi) of cytokeratin, which portrays good integrity of the Nigerian and Barbadian tissues. Scale bar 50 μm

Fig. 3

Kaiso subcellular localization and expression in Nigerian, Barbadian, AA, and CA TNBC tissues. (ai–viii) IHC images showing Kaiso localization to both the nucleus and cytoplasm of Nigerian, Barbadian, AA, and CA TNBC tissues. (b) Graphical representation of nuclear and cytoplasmic Kaiso expression in Nigerian (n = 19), Barbadian (n = 20), AA (n = 20), and CA (n = 39) TNBC tissues. Cytoplasmic Kaiso expression was significantly higher than nuclear Kaiso expression in the AA and CA TNBC cohorts but not in the Nigerian and Barbadian TNBC cohorts. Red arrows indicate nuclear Kaiso staining, while blue arrows indicate cytoplasmic Kaiso staining. Scale bar 50 μm. ns not significant, ^**** p < 0.0001

Fig. 4

Comparative analysis of nuclear Kaiso expression in Nigerian, Barbadian, AA, and CA TNBC tissues. Higher levels of nuclear Kaiso expression were detected in TNBC tissues of Nigerian, Barbadian, and AA compared with their Caucasian counterparts (a). Although no significant difference in nuclear Kaiso expression was observed between Nigerian versus Barbadian tissues, or between Barbadian versus AA tissues (b), there was a significant difference in nuclear Kaiso expression between Nigerian and AA TNBC tissues (c). ^* p < 0.05, ^** p < 0.005, ^*** p < 0.001