CTNNB1 exon 3 mutation

In conclusion, SCLECs frequently exhibit a mixed sertoliform/granulosa-like architecture and express epithelial markers, hormone receptors, nuclear β-catenin, and CDX2, with luminal CD10 positivity and CTNNB1 mutations. PAX8 expression is often lost, while other mesonephric, sex cord, and neuroendocrine markers are negative.

In the right setting, HA should be biopsied for molecular classification to help define patients who are at higher risk for malignant transformation and consequently those who may benefit from early surgical resection. Figure: T2-weighted MRI of Well Differentiated Adenocarcinoma of the Liver

Our findings suggest that targeted molecular testing has potential value in distinguishing well-differentiated HCC from benign lesions in small needle biopsies. All HCC cases demonstrated CTNNB1 and/or TERT promoter mutations, and while CTNNB1 mutations were infrequent in this small cohort of WDHL/Ns, the presence of TERT promoter mutation would strongly favor a diagnosis of HCC. A negative result, particularly in a small molecular panel is less informative; however, these small samples may be insufficient for larger, more comprehensive molecular testing.

These data provide a mechanistic understanding for bevacizumab-response in CTNNB1-mutated ECs demonstrated in GOG-86P. We hypothesize that overexpressed and secreted MMP7 potentially digests VEGFR-1, releasing VEGF-A, and increasing its availability. These activities may drive the formation of permeable vessels, which contributes to tumor progression, metastasis, and immune suppression. This mechanism is unique to EC and advocates for further clinical trials evaluating this treatment-related biomarker.

In summary, CTNNB1 mutations are associated with a unique melanocytic tumor type in benign tumors (nevi), which can be applied in a diagnostic setting. In advanced disease, no clear characteristics distinguishing CTNNB1-mutant from other melanomas were observed; however, studies of larger, optimally prospective, cohorts are warranted.

Although in this particular study, the lack of correlation between CTNNB1 exon 3 mutation and recurrence might be secondary to a small sample size, it also suggests the presence of other contributing factors. Thus, it helps set the foundation for larger series incorporating whole genome, transcriptome, proteome, and epigenome analyses to answer this clinically important question.

Our struggle for affordable prognostic markers is a continuous battle. The immunohistochemical beta-catenin nuclear expression is an ex- cellent replacement for CTNNBB1 exon 3 mutation in ECs and predicts prognosis in certain cases of ECs. We believe that future research will include this marker as part of the routine immunohistochemical panel for ECs.

CTNNB1 exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for CTNNB1 exon 3 mutation in these tumours.

In surgically resected HCA, 2 distinct GS patterns can reliably predict CTNNB1 exon 3 mutations, which are relevant because of the higher risk for malignant transformation. The third pattern, although specific, was less sensitive for the identification of exon 7/8 mutation, but the GS+/CD34- rim is a valuable aid to indicate either an exon 3 S45 or exon 7/8 mutation.