Expression of Com-1/P8 in human breast cancer and its relevance to clinical outcome and ER status

Abstract

Com-1 is a recently discovered molecule that has putative action on the metastatic nature of cancer cells. The molecular action and clinical implication in cancer and prognosis are yet to be established. The current study examined the role of Com-1 in a cohort of patients with breast cancer, with particular emphasis on its relationship with clinical outcomes and ER status. A panel of human breast cancer cell lines were tested. A cohort of breast cancer tumours (n-120) with matched normal non-neoplastic mammary tissues (n = 32) were used. Expression of Com-1 in cancer cells and mammary tissues were studied using conventional and real-time quantitative PCR. Expression profile was analysed against clinical information including tumour grade, staging, nodal status, ER status and survival of the patients. Statistical analysis was Mann-Whitney U-test and Cox Proportion analysis. Com-1 was expressed in breast cancer cell lines. Com-1 protein staining was primarily found in nucleus of epithelial cells of mammary tissues. Tumour cells in breast tissues exhibited a significant reduction in nuclear staining of Com-1, compared to normal epithelial cells (p = 0.0061). Breast tumour tissues expressed similar levels of Com-1, compared to normal non-neoplastic mammary tissues (p = 0.62). There was, however, a stepwise decrease in tumours from patients with predicted good, moderate, to poor prognosis (using Nottingham Prognostic Index) (166 +/- 135 copies of Com1 transcript, 44.3 +/- 36 and 0.64 +/- 0.24, respectively, p = 0.06 by Kruskal-Wallis test). Likewise, node positive tumours had low levels of Com-1, compared to node negative tumours. Tumours from patients who developed metastasis (11.4 +/- 7 copies of Com1 transcript), had local recurrence (41.5 +/- 3.7 copies of Com1 transcript), or who died of breast cancer (0.058 +/- 0.03 copies of Com1 transcript) had lower levels of Com-1, when compared to tumours from patients who remained disease free (156 +/- 129 copies of Com1 transcript). There was no significant correlation between Com-1 and overall survival or disease free survival. When ER status were taken into consideration, it was demonstrated that low levels of Com-1 in ER-beta positive tumours were highly correlated with shorter overall survival of the patients (p = 0.018) (median follow-up 120 months). Com-1 is a nuclear protein, whose expression is reduced in human breast cancer tissues and cancer cell lines. The loss of Com-1 protein is primarily from the nuclear compartment in cancer cells. The expression levels of Com-1 in breast tumours are correlated with the prognosis of the patients and with the long term overall survival in association with ER status.