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. 2023 Jun 27;18(6):e0287608.
doi: 10.1371/journal.pone.0287608. eCollection 2023.

PAK1 copy number in breast cancer-Associations with proliferation and molecular subtypes

Anette H Skjervold  1 , Marit Valla  1   2 , Borgny Ytterhus  1 , Anna M Bofin  1
Affiliations

PAK1 copy number in breast cancer-Associations with proliferation and molecular subtypes

Anette H Skjervold et al. PLoS One. .

Abstract

Introduction: P21-activated kinase 1 (PAK1) is known to be overexpressed in several human tumour types, including breast cancer (BC). It is located on chromosome 11 (11q13.5-q14.1) and plays a significant role in proliferation in BC. In this study we aimed to assess PAK1 gene copy number (CN) in primary breast tumours and their corresponding lymph node metastases, and associations between PAK1 CN and proliferation status, molecular subtype, and prognosis. In addition, we aimed to study associations between CNs of PAK1 and CCND1. Both genes are located on the long arm of chromosome 11 (11q13).

Methods: Fluorescence in situ hybridization for PAK1 and Chromosome enumeration probe (CEP)11 were used on tissue microarray sections from a series of 512 BC cases. Copy numbers were estimated by counting the number of fluorescent signals for PAK1 and CEP11 in 20 tumour cell nuclei. Pearson's x2 test was performed to assess associations between PAK1 CN and tumour features, and between PAK1 and CCND1 CNs. Cumulative risk of death from BC and hazard ratios were estimated in analysis of prognosis.

Results: We found mean PAK1 CN ≥4<6 in 26 (5.1%) tumours, and CN ≥ 6 in 22 (4.3%) tumours. The proportion of cases with copy number increase (mean CN ≥4) was highest among HER2 type and Luminal B (HER2-) tumours. We found an association between PAK1 CN increase, and high proliferation, and high histological grade, but not prognosis. Of cases with PAK1 CN ≥ 6, 30% also had CCND1 CN ≥ 6.

Conclusions: PAK1 copy number increase is associated with high proliferation and high histological grade, but not with prognosis. PAK1 CN increase was most frequent in the HER2 type and Luminal B (HER2-) subtype. PAK1 CN increase is associated with CN increase of CCND1.

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Conflict of interest statement

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Figures

Fig 1
Fig 1. Overview of study population and cases included in this study.
Fig 2
Fig 2. Fluorescence in situ hybridization using probes for CEP11 (fluorochrome SpectrumGreen) and PAK1 (fluorochrome SpectrumRed).
Fig 2 showing 2–3 copies of CEP11 and 6–8 copies of PAK1 in each tumour cell nucleus.
Fig 3
Fig 3. Cumulative incidence of death from breast cancer according to mean PAK1 copy number in primary breast cancer tumours.
Cumulative incidence curves show no significant association between PAK1 copy number and risk of death. A) Mean PAK1 copy number <4, ≥4<6 and ≥6. p = 0.39. B) Mean PAK1 copy number <4 and ≥4. p = 0.42.
Fig 4
Fig 4. Cumulative incidence of death from breast cancer according to copy numbers of PAK1 and CCND1, and co-amplification of PAK1 and CCND1.
Cumulative incidence curves show no significant association between PAK1 copy number, CCND1 copy number, and co-amplification of PAK1 and CCND1, and risk of death. p = 0,81.
See this image and copyright information in PMC

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