A research team led by Florence Boissière-Michotic from the Val d'Aurelle Cancer Institute in France presents a study in Modern Pathology that aims to identify the most reliable methods for KRAS mutation detection in specimens of colorectal cancer with low tumor cellularity. Because KRAS mutations have been linked to resistance to therapy with anti-epidermal growth factor receptor monoclonal antibodies, KRAS status assessment is required in metastatic colorectal cancer patients before treatment begins. Using high-resolution melting analysis/sequencing and the TheraScreen assay, the authors found that 39 percent of the surgical specimens presented KRAS mutations. "These results indicate that, in the case of post-radiochemotherapy surgical specimens of colorectal cancer with low tumor cellularity, pre-treatment biopsies might represent the most cost-effective option for reliable KRAS genotyping," Boissière-Michotic and her colleagues write. "The use of more sensitive assays, such as allele-specific PCR or laser microdissection, can be envisaged but with higher costs and longer delays."
Also in Modern Pathology, researchers at the University of British Columbia present their efforts to characterize BRCA1 and BRCA2 status in a series of ovarian carcinoma cases. The authors' aim was to identify differences in clinicopathological features, molecular characteristics, and outcome between the pelvic high-grade serous cancers with germline or somatic mutations in BRCA1 or BRCA2, methylation of BRCA1, and normal BRCA1 or BRCA2. Out of 131 women identified prospectively and who were undergoing surgical staging, 103 cases were high-grade serous carcinoma. And of these, 31 had germline or somatic BRCA1 or BRCA2 mutations, 21 had methylation of BRCA1, and in 51 there was no BRCA loss. A fourth group consisted of 28 cases of non-high-grade serous, none of which had BRCA loss. "Wild-type TP53 expression was associated with worse outcome in high-grade serous. BRCA loss (mutation/methylation) is a common event in the pelvic high-grade serous (50%). TP53 abnormalities and increased immune cell infiltrates are significantly more common in high-grade serous with germline and somatic mutations in BRCA1 or BRCA2, compared with tumors lacking BRCA abnormalities," the authors write.