Magic™ Anti-beta Catenin (N-termianl)(phospho S37) polyclonal antibody

Endometrial endometrioid carcinomas (EECs) with exon 3 CTNNB1 mutations characterize a more aggressive subset of tumors in patients with low-grade low-stage disease. Thus, prospectively identifying these cases may be clinically relevant. The aim of this study was to examine the feasibility of beta-catenin and Cyclin D1 immunohistochemistry to identify EECs harboring CTNNB1 mutations and to evaluate the clinicopathologic features of EECs with exon 3 CTNNB1 mutations. Thirty-nine CTNNB1 mutated EECs and 40 CTNNB1 wild-type EECs were identified from a cohort of previously sequenced endometrial carcinomas using a targeted next-generation sequencing panel. Immunohistochemistry for beta-catenin and Cyclin D1 was performed on all cases. Immunohistochemistry results were correlated with CTNNB1 mutation status and clinicopathologic parameters. Patients with CTNNB1 mutated EECs were younger than those with CTNNB1 wild-type (56.2 vs. 61.5 y; P=0.033). Nuclear beta-catenin expression correlated with exon 3 CTNNB1 mutation (P<0.0001) with a sensitivity of 91% and a specificity of 89%. Cyclin D1 expression correlated with CTNNB1 exon 3 mutation with relatively high specificity (90%) but low sensitivity (29%). Recurrence rate in patients with stage IA disease at diagnosis was significantly higher in patients whose tumors were CTNNB1 mutated compared with CTNNB1 wild-type (30% vs. 0%; P=0.025) and included distant metastases; all recurrent tumors in this group harbored exon 3 mutations and were histologically low grade (5 grade 1, 2 grade 2). Nuclear beta-catenin expression appears to be an acceptable proxy for CTNNB1 mutation.

PurposeAcross the globe, cervical cancer is the most common female malignancy, second only to breast cancer, as in both incidence and mortality. Currently, tissue biopsy is the gold standard to verify carcinoma of uterine cervix initial diagnosis and can be challenging due to its invasive nature. In this study, our objective was a noninvasive genetic panel for timely detection of cervical carcinoma and its progression using cell-free tumor DNA (ctDNA).MethodsTwenty-five cervical carcinoma patients were tested with a 50-gene tumor panel. ctDNA isolated from serum was checked for single-nucleotide variations (SNVs) or copy number alterations using targeted next-generation sequencing, with further validation of results by checking respective formalin-fixed paraffin-embedded tumor tissues for the same genetic alterations.ResultsOut of 50 genes, 32 were detected in the serum samples. The SNVs detected included TP53 in 52.3% patients, CDKN2A in 47.6%, PTEN and STK11 in 33.3% patients, BRAF and VHL in 28.5% patients, EGFR and SMAD4 in 19% patients; CTNNB1, GNAS, KIT, APC, PIK3CA in 14.28% patients; SMARCB1, SMO, RET, FBXW7, ERBB2, CSF1R, CDH1, AKT1, ATM, EBB4, FGFR3, FLT3, HRAS, JAK3, MET, NOTCH1, NPM1, KRAS, PTPN11 in 4.7 to 9.5% patients. On combining alterations in BRAF, CDKN2A, EGFR, PIK3CA, PTEN, STK11, TP53 and VHL genes, at least one of the genetic alterations was found in 100% patients.ConclusionThese findings illustrate that ctDNA is easily demonstrable and can be used as a surrogate for tissue biopsy in uterine cervix carcinoma.