Daisuke Tamura

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

AimsRecent 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 β‐catenin profile (β‐catenin signature). Through molecular analyses, we determined the incidence and clinicopathological significance of β‐catenin signatures.Methods and resultsWe evaluated 64 specimens of surgically removed bilateral fallopian tubes. Thirty‐three β‐catenin signatures were identified in 13 cases (20.3%); these patients were significantly younger than those without β‐catenin signatures (median ages of 44 and 57 years, respectively, P = 0.0317). No correlation between β‐catenin signature and any clinical factor was observed. CTNNB1 mutations were detected in three of eight β‐catenin signatures when tissues were microdissected and subjected to Sanger sequencing in two representative cases.ConclusionsThis is the first report of the CTNNB1 mutation in clusters of morphologically bland tubal epithelial cells. The results of this study indicate that β‐catenin signatures are common, and they may be a part of diverse molecular alterations occurring in normal tubal epithelium.

Distribution of cervical intraepithelial neoplasia is closely associated with HPV status and uterine position

AbstractAlthough cervical intraepithelial neoplasia (CIN) lesions are considered to be not randomly distributed across the cervix, but predominantly in the anterior wall, the clinicopathological etiology remains unknown. Herein, we aimed to elucidate the relationship between quantitatively measured area of CIN2/3 and cervical cancer associated factors by retrospective cohort study. We analyzed 235 consecutive therapeutic conization specimens dissected as a single intact section to determine CIN2/3 area and its correlation with both clinical risk factors including human papillomavirus (HPV) status (single or multiple infection) and uterine position defined by transvaginal ultrasound. Cervical wall was classified into three groups: anterior: (11, 12, 1, and 2 o'clock), posterior (5, 6, 7, and 8 o'clock) and lateral (3, 4, 9, and 10 o'clock). Multiple regression revealed that younger age and HPV16 status were significantly correlated with CIN2/3 area (p = 0.0224 and p = 0.0075, respectively). The Jonckheere‐Terpstra test showed a significant trend: CIN2/3 area was highest in the single HPV16 group, followed by the multiple HPV16 group and the non‐HPV16 group (p < 0.0001). CIN2/3 area in the anterior wall was statistically significantly larger than the posterior and lateral wall (p = 0.0059 and p = 0.0107, respectively). CIN2/3 area in the anterior wall was significantly greater with anteversion‐anteflexion than retroversion‐retroflexion (p = 0.0485), whereas CIN2/3 area in the posterior wall was significantly larger with retroversion‐retroflexion than anteversion‐anteflexion (p = 0.0394). In conclusion, the topographical distribution of CIN2/3 area is closely associated with patient age, high‐risk HPV status, especially single HPV16 infection and uterine position.