Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer

C. Coulson-Gilmer, M. P. Humphries, S. Sundara Rajan, A. Droop, S. Jackson, A. Condon, G. Cserni, L. B. Jordan, J. L. Jones, R. Kanthan, A. Di Benedetto, M. Mottolese, E. Provenzano, J. Kulka, A. M. Shaaban, A. M. Hanby, V. Speirs (Lead / Corresponding author)

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    Abstract

    Breast cancer can occur in either gender; however, it is rare in men, accounting for <1% of diagnosed cases. In a previous transcriptomic screen of male breast cancer (MBC) and female breast cancer (FBC) occurrences, we observed that Stanniocalcin 2 (STC2) was overexpressed in the former. The aim of this study was to confirm the expression of STC2 in MBC and to investigate whether this had an impact on patient prognosis. Following an earlier transcriptomic screen, STC2 gene expression was confirmed by RT-qPCR in matched MBC and FBC samples as well as in tumour-associated fibroblasts derived from each gender. Subsequently, STC2 protein expression was examined immunohistochemically in tissue microarrays containing 477 MBC cases. Cumulative survival probabilities were calculated using the Kaplan-Meier method and multivariate survival analysis was performed using the Cox hazard model. Gender-specific STC2 gene expression showed a 5.6-fold upregulation of STC2 transcripts in MBC, also supported by data deposited in Oncomine™. STC2 protein expression was a positive prognostic factor for disease-free survival (DFS; Log-rank; total p = 0.035, HR = 0.49; tumour cells p = 0.017, HR = 0.44; stroma p = 0.030, HR = 0.48) but had no significant impact on overall survival (Log-rank; total p = 0.23, HR = 0.71; tumour cells p = 0.069, HR = 0.59; stroma p = 0.650, HR = 0.87). Importantly, multivariate analysis adjusted for patient age at diagnosis, node staging, tumour size, ER, and PR status revealed that total STC2 expression as well as expression in tumour cells was an independent prognostic factor for DFS (Cox regression; p = 0.018, HR = 0.983; p = 0.015, HR = 0.984, respectively). In conclusion, STC2 expression is abundant in MBC where it is an independent prognostic factor for DFS.

    Original languageEnglish
    Pages (from-to)241-249
    Number of pages9
    JournalJournal of Pathology: Clinical Research
    Volume4
    Issue number4
    Early online date28 Jun 2018
    DOIs
    Publication statusPublished - Oct 2018

    Fingerprint

    Male Breast Neoplasms
    Breast Neoplasms
    Proportional Hazards Models
    Multivariate Analysis
    Gene Expression
    teleocalcin
    Neoplasms
    Survival
    Neoplasm Staging
    Survival Analysis
    Disease-Free Survival
    Proteins
    Up-Regulation

    Keywords

    • immunohistochemistry
    • male breast cancer
    • stanniocalcin 2
    • survival

    Cite this

    Coulson-Gilmer, C., Humphries, M. P., Sundara Rajan, S., Droop, A., Jackson, S., Condon, A., ... Speirs, V. (2018). Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer. Journal of Pathology: Clinical Research, 4(4), 241-249. https://doi.org/10.1002/cjp2.106
    Coulson-Gilmer, C. ; Humphries, M. P. ; Sundara Rajan, S. ; Droop, A. ; Jackson, S. ; Condon, A. ; Cserni, G. ; Jordan, L. B. ; Jones, J. L. ; Kanthan, R. ; Di Benedetto, A. ; Mottolese, M. ; Provenzano, E. ; Kulka, J. ; Shaaban, A. M. ; Hanby, A. M. ; Speirs, V. / Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer. In: Journal of Pathology: Clinical Research. 2018 ; Vol. 4, No. 4. pp. 241-249.
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    title = "Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer",
    abstract = "Breast cancer can occur in either gender; however, it is rare in men, accounting for <1{\%} of diagnosed cases. In a previous transcriptomic screen of male breast cancer (MBC) and female breast cancer (FBC) occurrences, we observed that Stanniocalcin 2 (STC2) was overexpressed in the former. The aim of this study was to confirm the expression of STC2 in MBC and to investigate whether this had an impact on patient prognosis. Following an earlier transcriptomic screen, STC2 gene expression was confirmed by RT-qPCR in matched MBC and FBC samples as well as in tumour-associated fibroblasts derived from each gender. Subsequently, STC2 protein expression was examined immunohistochemically in tissue microarrays containing 477 MBC cases. Cumulative survival probabilities were calculated using the Kaplan-Meier method and multivariate survival analysis was performed using the Cox hazard model. Gender-specific STC2 gene expression showed a 5.6-fold upregulation of STC2 transcripts in MBC, also supported by data deposited in Oncomine™. STC2 protein expression was a positive prognostic factor for disease-free survival (DFS; Log-rank; total p = 0.035, HR = 0.49; tumour cells p = 0.017, HR = 0.44; stroma p = 0.030, HR = 0.48) but had no significant impact on overall survival (Log-rank; total p = 0.23, HR = 0.71; tumour cells p = 0.069, HR = 0.59; stroma p = 0.650, HR = 0.87). Importantly, multivariate analysis adjusted for patient age at diagnosis, node staging, tumour size, ER, and PR status revealed that total STC2 expression as well as expression in tumour cells was an independent prognostic factor for DFS (Cox regression; p = 0.018, HR = 0.983; p = 0.015, HR = 0.984, respectively). In conclusion, STC2 expression is abundant in MBC where it is an independent prognostic factor for DFS.",
    keywords = "immunohistochemistry, male breast cancer, stanniocalcin 2, survival",
    author = "C. Coulson-Gilmer and Humphries, {M. P.} and {Sundara Rajan}, S. and A. Droop and S. Jackson and A. Condon and G. Cserni and Jordan, {L. B.} and Jones, {J. L.} and R. Kanthan and {Di Benedetto}, A. and M. Mottolese and E. Provenzano and J. Kulka and Shaaban, {A. M.} and Hanby, {A. M.} and V. Speirs",
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    Coulson-Gilmer, C, Humphries, MP, Sundara Rajan, S, Droop, A, Jackson, S, Condon, A, Cserni, G, Jordan, LB, Jones, JL, Kanthan, R, Di Benedetto, A, Mottolese, M, Provenzano, E, Kulka, J, Shaaban, AM, Hanby, AM & Speirs, V 2018, 'Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer', Journal of Pathology: Clinical Research, vol. 4, no. 4, pp. 241-249. https://doi.org/10.1002/cjp2.106

    Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer. / Coulson-Gilmer, C.; Humphries, M. P.; Sundara Rajan, S.; Droop, A.; Jackson, S.; Condon, A.; Cserni, G.; Jordan, L. B.; Jones, J. L.; Kanthan, R.; Di Benedetto, A.; Mottolese, M.; Provenzano, E.; Kulka, J.; Shaaban, A. M.; Hanby, A. M.; Speirs, V. (Lead / Corresponding author).

    In: Journal of Pathology: Clinical Research, Vol. 4, No. 4, 10.2018, p. 241-249.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer

    AU - Coulson-Gilmer, C.

    AU - Humphries, M. P.

    AU - Sundara Rajan, S.

    AU - Droop, A.

    AU - Jackson, S.

    AU - Condon, A.

    AU - Cserni, G.

    AU - Jordan, L. B.

    AU - Jones, J. L.

    AU - Kanthan, R.

    AU - Di Benedetto, A.

    AU - Mottolese, M.

    AU - Provenzano, E.

    AU - Kulka, J.

    AU - Shaaban, A. M.

    AU - Hanby, A. M.

    AU - Speirs, V.

    N1 - Funding: Breast Cancer Now. Grant Number: TBLEE2017; Yorkshire Cancer Research. Grant Number: L378

    PY - 2018/10

    Y1 - 2018/10

    N2 - Breast cancer can occur in either gender; however, it is rare in men, accounting for <1% of diagnosed cases. In a previous transcriptomic screen of male breast cancer (MBC) and female breast cancer (FBC) occurrences, we observed that Stanniocalcin 2 (STC2) was overexpressed in the former. The aim of this study was to confirm the expression of STC2 in MBC and to investigate whether this had an impact on patient prognosis. Following an earlier transcriptomic screen, STC2 gene expression was confirmed by RT-qPCR in matched MBC and FBC samples as well as in tumour-associated fibroblasts derived from each gender. Subsequently, STC2 protein expression was examined immunohistochemically in tissue microarrays containing 477 MBC cases. Cumulative survival probabilities were calculated using the Kaplan-Meier method and multivariate survival analysis was performed using the Cox hazard model. Gender-specific STC2 gene expression showed a 5.6-fold upregulation of STC2 transcripts in MBC, also supported by data deposited in Oncomine™. STC2 protein expression was a positive prognostic factor for disease-free survival (DFS; Log-rank; total p = 0.035, HR = 0.49; tumour cells p = 0.017, HR = 0.44; stroma p = 0.030, HR = 0.48) but had no significant impact on overall survival (Log-rank; total p = 0.23, HR = 0.71; tumour cells p = 0.069, HR = 0.59; stroma p = 0.650, HR = 0.87). Importantly, multivariate analysis adjusted for patient age at diagnosis, node staging, tumour size, ER, and PR status revealed that total STC2 expression as well as expression in tumour cells was an independent prognostic factor for DFS (Cox regression; p = 0.018, HR = 0.983; p = 0.015, HR = 0.984, respectively). In conclusion, STC2 expression is abundant in MBC where it is an independent prognostic factor for DFS.

    AB - Breast cancer can occur in either gender; however, it is rare in men, accounting for <1% of diagnosed cases. In a previous transcriptomic screen of male breast cancer (MBC) and female breast cancer (FBC) occurrences, we observed that Stanniocalcin 2 (STC2) was overexpressed in the former. The aim of this study was to confirm the expression of STC2 in MBC and to investigate whether this had an impact on patient prognosis. Following an earlier transcriptomic screen, STC2 gene expression was confirmed by RT-qPCR in matched MBC and FBC samples as well as in tumour-associated fibroblasts derived from each gender. Subsequently, STC2 protein expression was examined immunohistochemically in tissue microarrays containing 477 MBC cases. Cumulative survival probabilities were calculated using the Kaplan-Meier method and multivariate survival analysis was performed using the Cox hazard model. Gender-specific STC2 gene expression showed a 5.6-fold upregulation of STC2 transcripts in MBC, also supported by data deposited in Oncomine™. STC2 protein expression was a positive prognostic factor for disease-free survival (DFS; Log-rank; total p = 0.035, HR = 0.49; tumour cells p = 0.017, HR = 0.44; stroma p = 0.030, HR = 0.48) but had no significant impact on overall survival (Log-rank; total p = 0.23, HR = 0.71; tumour cells p = 0.069, HR = 0.59; stroma p = 0.650, HR = 0.87). Importantly, multivariate analysis adjusted for patient age at diagnosis, node staging, tumour size, ER, and PR status revealed that total STC2 expression as well as expression in tumour cells was an independent prognostic factor for DFS (Cox regression; p = 0.018, HR = 0.983; p = 0.015, HR = 0.984, respectively). In conclusion, STC2 expression is abundant in MBC where it is an independent prognostic factor for DFS.

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    Coulson-Gilmer C, Humphries MP, Sundara Rajan S, Droop A, Jackson S, Condon A et al. Stanniocalcin 2 expression is associated with a favourable outcome in male breast cancer. Journal of Pathology: Clinical Research. 2018 Oct;4(4):241-249. https://doi.org/10.1002/cjp2.106