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BMC Cancer
2021 Feb 23;211:186. doi: 10.1186/s12885-021-07893-7.
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High nuclear TPX2 expression correlates with TP53 mutation and poor clinical behavior in a large breast cancer cohort, but is not an independent predictor of chromosomal instability.
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BACKGROUND: Targeting Protein for Xenopus Kinesin Like Protein 2 (TPX2) is a microtubule associated protein that functions in mitotic spindle assembly. TPX2 also localizes to the nucleus where it functions in DNA damage repair during S-phase. We and others have previously shown that TPX2 RNA levels are strongly associated with chromosomal instability (CIN) in breast and other cancers, and TPX2 RNA levels have been demonstrated to correlate with aggressive behavior and poor clinical outcome across a range of solid malignancies, including breast cancer.
METHODS: We perform TPX2 IHC on a cohort of 253 primary breast cancers and adopt a clinically amenable scoring system to separate tumors into low, intermediate, or high TPX2 expression. We then correlate TPX2 expression against diverse pathologic parameters and important measures of clinical outcome, including disease-specific and overall survival. We link TPX2 expression to TP53 mutation and evaluate whether TPX2 is an independent predictor of chromosomal instability (CIN).
RESULTS: We find that TPX2 nuclear expression strongly correlates with high grade morphology, elevated clinical stage, negative ER and PR status, and both disease-specific and overall survival. We also show that increased TPX2 nuclear expression correlates with elevated ploidy, supernumerary centrosomes, and TP53 mutation. TPX2 nuclear expression correlates with CIN via univariate analyses but is not independently predictive when compared to ploidy, Ki67, TP53 mutational status, centrosome number, and patient age.
CONCLUSIONS: Our findings demonstrate a strong correlation between TPX2 nuclear expression and aggressive tumor behavior, and show that TPX2 overexpression frequently occurs in the setting of TP53 mutation and elevated ploidy. However, TPX2 expression is not an independent predictor of CIN where it fails to outperform existing clinical and pathologic metrics.
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Fig. 1. a Histogram depicting percent of cells with TPX2 cytoplasmic expression in all scored tumors. b, Histogram depicting percent of all cells with TPX2 nuclear expression in all scored tumors. c, Representative images depicting H&E and TPX2 IHC from tumors with low, intermediate, and high TPX2 nuclear expression (magnification: 100X, insets 400X)
Fig. 2. a Tumor size versus TPX2 nuclear expression. b, Ki67 index versus TPX2 nuclear expression. c, Average number of centrosomes per cell versus TPX2 nuclear expression. d, Percent of tumors with aberrant p53 immunohistochemical staining versus TPX2 nuclear expression. e, Average ploidy versus TPX2 nuclear expression. f, Percentage of tumors with CIN versus TPX2 nuclear expression. *P < 0.0001, **P < 0.005
Fig. 3. a Kaplan-Meier curve showing relationship between disease-specific survival and TPX2 nuclear expression (log rank P < 0.0001). b, Kaplan-Meier curve depicting relationship between overall survival TPX2 nuclear expression (log rank P < 0.005)
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