Prognostic significance of molecular genetic aberrations on chromosome segment 11p15.5 in non-small-cell lung cancer

Abstract

Purpose: The assessment of prognosis and decisions on treatment for patients with non-small-cell lung cancer (NSCLC) are determined on the basis of disease stage and performance status. NSCLC frequently manifests loss of heterozygosity (LOH) at chromosome segment 11p15.5. Whether LOH at 11p15.5 is an independent prognostic variable has yet to be determined.

Patients and methods: We developed five novel markers, which can be assessed by polymerase chain reaction and restriction enzyme digestion. LOH at 11p15.5 was assessed in 193 patients who underwent surgical resection for pathologic stage I and II of the disease.

Results: LOH at 11p15.5 was associated with poor survival (P =.021). Multivariate logistic regression analysis showed that after disease stage, performance status, weight loss, sex, age at diagnosis, and smoking history were controlled for, patients with LOH were two times more likely to die than those without LOH (relative risk [RR] = 2.01, P =.021). Cox regression analysis with disease stage and LOH revealed that the survival of patients with stage I disease and LOH was similar to the survival of patients with stage II disease, and it was significantly worse than the survival of stage I patients without LOH (RR = 2.38, P =.038).

Conclusion: LOH in a 310-kb region on chromosome segment 11p15.5 that includes the gene for the regulatory subunit of the enzyme ribonucleotide reductase is highly predictive of poor survival from NSCLC. The future utility of analysis of the allelic status of this region may involve treatment decisions, such as the use of neoadjuvant and adjuvant chemotherapy for patients with stage I disease.