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Objectives CTNNB1 exon 3 mutations have shown independent prognostic value in endometrial cancer. We aimed to assess whether nuclear β-catenin expression is an accurate surrogate, as immunohistochemistry is cheaper, faster, and more widely applicable than sequencing. Methods A systematic review was performed by searching electronic databases for all studies assessing the association between β-catenin immunohistochemical expression and CTNNB1 mutations. Meta-analysis of diagnostic accuracy was performed by calculating sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR–), diagnostic odds ratio (DOR), and area under the curve (AUC) on summary receiver operating characteristic curves. Results Fifteen observational studies with 1,158 endometrial carcinomas were included. Pooled estimates showed sensitivity = 0.88, specificity = 0.85, LR+ = 4.57, LR– = 0.20, DOR = 27.16, and high diagnostic accuracy (AUC = 0.91). Conclusions Nuclear expression of β-catenin is an accurate immunohistochemical surrogate of CTNNB1 exon 3 mutations and thus might be considered in the risk stratification of endometrial cancer. [ABSTRACT FROM AUTHOR]

Background Sanger sequencing (SS) of PCR products is still the most frequent method to test colorectal cancer for KRAS mutations in routine practice. Methods An audit of SS on 1720 routine cases was carried out, taking into account age, gender, specimen type (resection vs biopsies), tumour site ( primary vs metastasis), tumour stage, neoplastic cells abundance (>30% vs <30%) and fixation type (buffered formalin vs simple formalin). In a subset of 50 wild-type (WT) patients correlations between SS findings and response rate (RR), progression-free survival (PFS) and overall survival (OS) were also evaluated. Results The tests were informative in 1691 cases (98.3%). Mutations were detected in 671 cases (39.6%). No significant differences in mutation rates were observed with respect to age (p=0.2), gender ( p=0.2), specimen type (p=0.3) and formalin fixation ( p=0.08). Conversely, KRAS mutant rate was higher in metastatic tissue (50% vs 39%, p=0.02), in samples with over 30% of neoplastic cells (43.4% vs 26.6%, p=0.02) and in tumours tested in stage IV ( p=0.05). The RR of SS KRAS WT patients was 26% (one complete and 12 partial responses). The disease control rate (objective responses plus stable disease) was 56%. Median PFS was 4.4 months and median OS was 10.4 months. Conclusions Pathological criteria that make SS a more robust method for KRAS testing and treatment response prediction are neoplastic cell abundance, metastatic tissue sample and stage IV primary tumour. [ABSTRACT FROM AUTHOR]