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    Phenotypic characterisation of breast cancer: the role of CDC42

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    Author
    Chrysanthou, E; Gorringe, KL; Joseph, C; Craze, M; Nolan, CC; Diez-Rodriguez, M; Green, AR; Rakha, EA; Ellis, IO; Mukherjee, A
    Date
    2017-07-01
    Source Title
    Breast Cancer Research and Treatment
    Publisher
    SPRINGER
    University of Melbourne Author/s
    Gorringe, Kylie
    Affiliation
    Sir Peter MacCallum Department of Oncology
    Metadata
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    Document Type
    Journal Article
    Citations
    Chrysanthou, E., Gorringe, K. L., Joseph, C., Craze, M., Nolan, C. C., Diez-Rodriguez, M., Green, A. R., Rakha, E. A., Ellis, I. O. & Mukherjee, A. (2017). Phenotypic characterisation of breast cancer: the role of CDC42. BREAST CANCER RESEARCH AND TREATMENT, 164 (2), pp.317-325. https://doi.org/10.1007/s10549-017-4267-8.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/259171
    DOI
    10.1007/s10549-017-4267-8
    Abstract
    PURPOSE: The molecular landscape of breast cancer (BC), especially of the Luminal A subtype, remains to be fully delineated. Transcriptomic data show that Luminal A tumours are enriched for aberrant expression of genes in the cell division control 42 homolog (CDC42) pathway. This study aims to investigate the protein expression of CDC42 in BC and assess its clinicopathological significance. METHODS: Expression of CDC42 protein was examined by immunohistochemistry on tissue microarrays in a well-characterised cohort of 895 early-stage (I-IIIa) primary invasive BCs. RESULTS: CDC42 expression was observed in both the cytoplasm and the nucleus of BC cells. High nuclear CDC42 expression demonstrated a significant correlation with ER-positive, low-grade tumours and was more common in the lobular histological subtype (all p < 0.001). In contrast, cytoplasmic CDC42 showed increased expression in the ductal subtype (p < 0.001) and correlated with negative prognostic features such as larger size, higher grade (p < 0.05) and higher Ki67 labelling index (p = 0.001). Nuclear CDC42 expression was associated with a longer BC-specific survival in all cases (p = 0.025) and in luminal ER-positive tumours (p = 0.011). In multivariate analyses including size, grade, lymph node stage and intrinsic subtype, CDC42 was an independent prognostic factor (p = 0.032). CONCLUSION: The results indicate that CDC42 is an important molecule in luminal BC, with prognostic significance.

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