Patients with CRC with Nm23-H1(+)/p53(-) tumors had increased survival rates, with a five-year overall survival rate of 83.8% and a five-year disease-free survival rate of 70.2%.
Kaplan-Meier estimates analysis suggested that EGFR expression was as a negative predictor, the median PFS of patients with EGFR high expression was 21.73 months, and the median PFS of patients with low EGFR expression was 57.83 months (χ2=20.880, P<0.001); nm23 expression was positive predictive factor for the prognosis of patients with colorectal carcinoma, the median PFS of patients with high nm23 expression was 37.77 months, and the median PFS was 21.47 months in the patients with low nm23 expression (χ2=7.364, P=0.007).
An immunohistochemical study on 382 tumour and normal samples deposited onto a tissue microarray subsequently validated the upregulation of NM23 in CRC and a downregulation in poor prognosis tumours.
Our results indicate that DNA aneuploidy and high SPF are associated in CRC with a poor clinical 5-year outcome, while in contrast the prognostic role of TP53 and NM23-H1 expression is still to be clarified.
In conclusion, this study demonstrates that the DNA content and genetic markers c-myc, c-erbB-2, EGFr, H-ras, p53, PCNA, and nm23 do not predict survival after potentially curative resection of hepatic metastases from CRC.
Our findings suggest that genomic alterations in the 17q21-23 region may affect prognosis of CRC as well as regulation of the nm23 protein expression via an unknown underlying mechanism.
Loss of heterozygosity (LOH) at the nm23 locus has been shown previously in ovarian carcinomas, and genetic alterations at both the 3p and 5q loci have been reported in colorectal carcinomas.
Allelic imbalance at NME1 in microdissected primary and metastatic human colorectal carcinomas is frequent but not associated with metastasis to lymph nodes or liver.
The purpose of this study was to analyze the allelic deletions of Nm23 and p53 in colorectal carcinomas and to assess their prognostic significance in the evolution of the patients.
In order to investigate its role in the progression of colorectal cancer, we analysed 22 liver metastases of this malignancy with respect to mutational changes, loss of heterozygosity and expression levels of nm23-H1.
Tests with probe YNZ 22.1, near p53, showed no significant association with distant metastases. nm23-H1 may be, or may be located near, a late-acting suppressor gene in colorectal carcinoma, in which deletions may have prognostic value.