Clinicopathological and molecular analyses of linearly expanded epithelial cells with β‐catenin alterations, “β‐catenin signature”, in the normal fallopian tube

Abstract

Clinicopathological and molecular analyses of linearly expanded epithelial cells with b-catenin alterations, "b-catenin signature", in the normal fallopian tube Aims: Recent advances in next-generation sequencing have made it clear that clonal expansion of cells harbouring driver gene mutations occurs in physiologically normal epithelium. Molecular analysis of tubal epithelium has been almost exclusively confined to the TP53 pathway, which is involved in serous carcinogenesis. Other oncogenic events have not been explored in detail. Here, we report the linear expansion of fallopian tubal epithelial cells exhibiting an altered b-catenin profile (b-catenin signature). Through molecular analyses, we determined the incidence and clinicopathological significance of b-catenin signatures. Methods and results: We evaluated 64 specimens of surgically removed bilateral fallopian tubes. Thirty-three b-catenin signatures were identified in 13 cases (20.3%); these patients were significantly younger than those without b-catenin signatures (median ages of 44 and 57 years, respectively, P = 0.0317). No correlation between b-catenin signature and any clinical factor was observed. CTNNB1 mutations were detected in three of eight b-catenin signatures when tissues were microdissected and subjected to Sanger sequencing in two representative cases. Conclusions: This is the first report of the CTNNB1 mutation in clusters of morphologically bland tubal epithelial cells. The results of this study indicate that b-catenin signatures are common, and they may be a part of diverse molecular alterations occurring in normal tubal epithelium.

β‐catenin signatures in the fallopian tube: an emerging concept

“…In this issue, Koyama et al . expand upon these observations and study the prevalence, morphology and distribution of β‐catenin signatures in greater detail by examining 64 bilateral fallopian tubes, which were entirely submitted using the sectioning and extensively examining the fimbriated end (SEE‐FIM) protocol, and performing immunohistochemical staining for β‐catenin 8 . Interestingly, they found foci of abnormal β‐catenin staining (‘β‐catenin signatures’) in more than 20% of the tubes; none of these exhibited an increased MIB1 proliferation index.…”

“…6,7 In this issue, Koyama et al expand upon these observations and study the prevalence, morphology and distribution of b-catenin signatures in greater detail by examining 64 bilateral fallopian tubes, which were entirely submitted using the sectioning and extensively examining the fimbriated end (SEE-FIM) protocol, and performing immunohistochemical staining for b-catenin. 8 Interestingly, they found foci of abnormal b-catenin staining ('b-catenin signatures') in more than 20% of the tubes; none of these exhibited an increased MIB1 proliferation index. The frequency was not significantly higher in the fimbrial portion of the tube, and most of the signatures consisted of a linear proliferation of secretory cells (a small proportion also contained ciliated cells), some of which were pseudostratified with an endometrioid-like morphology; this endometrioidlike morphology has also been noted previously, and occasional cases have contained squamous morules ( Figure 1).…”