Assessing the TP53 marker type in patients treated with or without neoadjuvant chemotherapy for resectable colorectal liver metastases: A p53 Research Group study. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Pilat, N.; Grünberger, T.; Längle, F.; Mittlböck, M.; Perisanidis, B.; Kappel, S.; Wolf, B.; Starlinger, P.; Kührer, I.; Mühlbacher, F.; Kandioler, D.
• Is Part Of: European journal of surgical oncology. Volume 41:Issue 5(2015:May)
• Page Start: 683
• Page End: 689
• Publication Date: 2015-05
• Subjects: Oncology -- Periodicals; Cancer -- Surgery -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- surgery -- Periodicals; Cancer -- Chirurgie -- Périodiques; Cancérologie -- Périodiques; Oncologie; Chirurgie (geneeskunde); Electronic journals; Electronic journals -- Sciences; Electronic journals -- Medicine; Electronic journals; 616.994059005
• DOI: 10.1016/j.ejso.2015.02.003
• Languages: English
• ISSNs: 0748-7983

Abstract

<abstract xml:lang="en" abstract-type="author" id="abs0010"> <title id="sectitle0010">Abstract</title> <sec> <p id="abspara0010">The type of a biomarker – whether it is prognostic or predictive – is frequently not known, although such information is crucial for assessing the clinical value of a marker.</p> <p id="abspara0015">In order to evaluate the type of marker TP53 is, we identified a cohort of 76 patients with colorectal liver metastases (CLM), homogeneously staged as resectable, who had been treated either with or without fluorouracil-based neoadjuvant chemotherapy. The TP53 genotype was assessed retrospectively from paraffin-embedded, diagnostic tumour biopsies using a standardised, p53 gene-specific sequencing protocol (mark53<sup>®</sup> kit).</p> <p id="abspara0020">The overall median survival was 44.2 months, and the overall TP53 mutation frequency was 55%. A significant interaction was observed between chemotherapy and TP53 status (<italic>P</italic> = 0.045). To illustrate this effect, the 51 patients with and the 25 patients without neoadjuvant chemotherapy were described separately. In patients with neoadjuvant chemotherapy, mutated TP53 was significantly associated with poor survival (<italic>P</italic> = 0.0025), resulting in five-year survival rates of 22%, compared to 60% in patients with normal TP53. The hazard ratio was 3.12 (95% confidence intervals (CI): 1.46–6.95) to the disadvantage of TP53-mutated patients and 5.49 (<italic>P</italic> = 0.0001; 95% CI: 2.28–13.24) after adjustment for known prognostic factors. In patients treated with surgery alone, a mutated TP53 did not have a negative effect on survival (<italic>P</italic> = 0.54).</p> <p id="abspara0025">A mutated TP53 status independently predicted survival disadvantage in CLM patients in the presence, but not in the absence, of neoadjuvant chemotherapy. Our data suggest that TP53 might be a pure predictive marker.</p> </sec> </abstract>