Patocs A et al. (2007) Breast-cancer stromal cells with TP53 mutations and nodal metastases. N Engl J Med 357: 2543–2551

Studies have suggested that cross-talk between neoplasms and the surrounding microenvironment can regulate tumor behavior. High-frequency mutations of TP53 have been identified in neoplastic breast epithelium and the surrounding stroma. A study by Patocs et al. has evaluated the role of genomic alterations of TP53 in epithelial and stromal cells in hereditary and sporadic breast cancers.

The authors assessed TP53 mutation status, loss of heterozygosity (LOH) and allelic imbalance in 43 and 175 DNA samples from patients with hereditary and sporadic breast cancer, respectively. TP53 mutations were identified in 74.4% of samples from the hereditary-cancer group and 42.3% of samples from the sporadic-cancer group (P <0.001). TP53 mutations in epithelium or stroma were associated with increased frequency of allelic imbalance or LOH in both groups; however, the association was more prominent in the sporadic group. In the sporadic group, 66 microsatellite loci linked to LOH or allelic imbalance were associated with mutated TP53; by contrast, only one locus (2p25.1) in stromal cells from the hereditary group was associated with mutated TP53. In the sporadic group, stromal TP53 mutation status was significantly associated with lymph-node metastases (P = 0.003). Finally, five stromal loci in the sporadic tumors were associated with nodal metastases in the absence of TP53 mutations.

The authors conclude that stroma-specific LOH or allelic imbalance is associated with TP53 mutation status and nodal metastases in sporadic but not hereditary breast cancer.