Researchers led by Seoul National University's So Yeon Park report in Modern Pathology that a portion of HER2-amplified breast cancers have varying levels of HER2 gene amplification in different parts of the tumor. Using tissue microarrays, the researchers examined regional heterogeneity and genetic heterogeneity of HER2 gene amplification in 96 invasive breast cancers. Of the tumors they studied, 18 percent had regional heterogeneity and 11 percent had genetic heterogeneity. They further report that patients with intratumoral heterogeneity had shorter disease-free survival times than patients with homogeneous amplification levels, and that intratumoral heterogeneity may be an independent, prognostic factor for disease-free survival. This suggests, the authors add that "intratumoral heterogeneity of HER2 gene amplification may be associated with breast cancer progression."

Also in the current issue of Modern Pathology, the University of California, San Francisco's Sanjay Kakar and colleagues write that chromosomal instability due to loss of heterozygosity is found in most cases of signet ring cell carcinoma. In their study, the researchers looked at microsatellite-instability status, methylation, BRAF mutation, KRAS mutation, and chromosomal instability in 33 signet ring cell carcinoma cases, and how the status of each factor correlated with survival. They observed the BRAF V600E mutation in a third of signet ring cell carcinomas and note that it is associated with poor outcome in microsatellite-stable signet ring cell carcinoma cases, though not in in high-level microsatellite-unstable tumors. "The high frequency of methylation and BRAF V600E mutation suggests that many signet ring cell carcinomas may be related to the serrated pathway of carcinogenesis," the researchers add.