Yuhong Ye

XPO1‐Mediated EIF1AX Cytoplasmic Relocation Promotes Tumor Migration and Invasion in Endometrial Carcinoma

Dysregulation of eukaryotic translation initiation factor 1A, X‐linked (EIF1AX), has been implicated in the pathogenesis of some cancers. However, the role of EIF1AX in endometrial carcinoma (EC) remains unknown. We investigated the EIF1AX expression in EC patients and assessed its tumorigenesis‐associated function and nucleocytoplasmic transport mechanism in vitro and in vivo. The results indicated that the cytoplasmic EIF1AX expression showed a gradual increase when going from endometrium normal tissue, simple endometrial hyperplasia, complex endometrial hyperplasia, and endometrial atypical hyperplasia to EC, while vice versa for the nuclear EIF1AX expression. In addition, the cytoplasmic EIF1AX expression was positively correlated with histologic type, high International Federation of Gynecology and Obstetrics (FIGO) grade, advanced FIGO stage, deeper infiltration, high Ki67 index, and shorter recurrence‐free survival in EC patients. In vitro, short hairpin RNA‐mediated EIF1AX depletion or SV40NLS‐mediated EIF1AX import into the nucleus in multiple human EC cells potently suppressed cell migration and invasion, epithelial‐mesenchymal transition, and lung metastasis. Moreover, exportin 1 induced the transport of EIF1AX from the nucleus to the cytoplasm that could be inhibited by leptomycin B treatment or the mutation in the EIF1AX location sequence. These results demonstrate that cytoplasmic EIF1AX may play a key role in the incidence and promotion of EC, and thus, targeting EIF1AX or its nucleocytoplasmic transport process may offer an effective new therapeutic approach to EC.

Assessment of microorganism detection in ThinPrep Papanicolaou tests utilizing the Hologic Genius Digital Diagnostics System

Abstract Objective The Hologic Genius Digital Diagnostics System (HGDDS) analyzes ThinPrep Papanicolaou (Pap) tests (TPPTs) to assist in detecting cervical lesions. The aim of this study was to determine the sensitivity of the HGDDS in identifying commonly diagnosed microorganisms in Pap tests. Methods A total of 305 TPPT cases were selected from Magee Women’s Hospital, University of Pittsburgh, consisting of 244 cases with microorganism diagnoses (a total of 262 cases of Actinomyces, Candida spp, herpes simplex virus [HSV], and Trichomonas) and 61 cases without microorganisms. Slides were scanned and then subjected to artificial intelligence (AI) analysis using the HGDDS and subsequently reviewed on a digital workstation by a cytologist, followed by a resident and a cytopathologist who made the final diagnoses. Results Diagnosis using the HGDDS demonstrated high sensitivity across all microorganisms (95.4%). Herpes simplex virus detection was comparatively lower (82.5%). Of the microorganisms, 85.2% were displayed in the first gallery of 30 images within row 5, 7.2% presented in the first gallery outside of row 5, and 7.6% presented in the hidden gallery of images. Among the 12 cases with missed diagnoses, 3 of 5 Candida spp and 3 of 7 HSV organisms were not presented within the 60 images selected by HGDDS. In another 6 cases, microorganisms were found within the 60 fields, but none were present in row 5. Conclusions Very high sensitivity was observed for TPPTs across 3 of 4 common microorganisms on the HGDDS, although sensitivity was relatively lower for detecting HSV. Understanding morphologic patterns of various microorganisms in detection misses by the HGDDS may help guide the implementation of AI-assisted cervical cancer screening systems.

Juvenile Granulosa Cell Tumors of the Ovary

Abstract Objective To explore the clinical and pathologic features of ovarian juvenile granulosa cell tumors (JGCTs). Methods Clinical data, histopathologic observations, immunohistochemical results, FOXL2 mutation status, and follow-up information of 7 JGCT cases were studied. Results The patients most commonly presented with abdominal distension and pain (5 cases), followed by precocious puberty (1 case) and a pelvic mass (1 case). Six patients had stage I disease, and 1 had stage IV disease. The microscopic examinations typically showed lobular growth punctuated by variably sized and shaped follicles. Rare features included a reticular-cystic appearance mimicking a yolk sac tumor (2 cases), a lobular appearance similar to a sclerosing stromal tumor (1 case), strands and cords (1 case), pseudopapillary appearance (2 cases), spindle cell appearance (1 case), microcystic appearance (1 case), hobnail cells (1 case), and rhabdomyoid cells (1 case). No FOXL2 mutation was encountered. After a median follow-up of 53 months, only 1 patient with a strongly diffuse TP53-positive tumor died of the disease, and 2 successfully had babies. Conclusions JGCT is a rare neoplasm with a wide morphologic spectrum and is easily confused with other tumors. Familiarity with the characteristics, rare atypical appearances, and immunohistochemical results may aid in obtaining a correct diagnosis.