Exploring adenoid basal carcinoma to squamous cell carcinoma of the uterine cervix transformation using spatial transcriptomics

Adenoid basal carcinoma (ABC) is a rare cervical tumor that generally carries a favorable prognosis. However, when ABC is mixed with an invasive carcinoma, particularly squamous cell carcinoma (SCC), the prognosis is poor. Moreover, transitional nests (TNs), which are frequently observed in mixed tumors, likely represent an intermediate stage between ABC and SCC. Therefore, elucidating the relationship between these subtypes through histomorphological and molecular biological analysis is essential for guiding effective therapeutic strategies. To this end, we conducted a retrospective study involving 20 cases of ABC, most of which were accompanied by one or more of the three subtypes of SCC, TN, and high‐grade squamous intraepithelial lesion (HSIL). Histomorphological analysis revealed that TN were frequently located in the transitional zones between classic ABC and SCC, while maintaining a distinct spatial separation from classic HSIL regions. The central areas of TNs exhibit cytological atypia resembling that of SCC, often surrounded by a cuff‐like arrangement of basaloid cells, which express the basal cell marker BCL‐2. We performed digital spatial profiling (DSP) analysis on four cases exhibiting concurrent ABC, TN, SCC, and HSIL. We identified the differentially expressed genes CK13 and SCCA2 , which distinguish TN from ABC, SCC, and HSIL, and validated these findings by immunohistochemistry. This study investigates the relationship between ABC and SCC and demonstrates the disease spectrum of ABC progressing to SCC through a transitional phase represented by TNs. This finding provides novel insights into the pathogenesis of SCC. In addition, we believe that total hysterectomy may be an appropriate strategy when ABC is accompanied by a TN. However, larger‐scale studies will still be needed in the future to guide clinical decisions because of the limited sample size.