Aberrant GATA3 Staining in Prostatic Adenocarcinoma: A Potential Diagnostic Pitfall.

Distinguishing between poorly differentiated urothelial carcinoma and high-grade prostatic adenocarcinoma is a common challenge in genitourinary pathology, particularly when the tumor involves the bladder neck or prostatic urethra. Clinically, the distinction between these 2 tumors can also be difficult. Proper diagnosis in these patients is essential as they have differing prognoses and clinical management. GATA3 is thought to be a sensitive and relatively specific marker of urothelial carcinoma. However, there is scant data regarding GATA3 labeling of high-grade prostatic adenocarcinoma. The aim of this study is to describe rare cases with strong aberrant GATA3 staining in prostatic adenocarcinoma as a potential diagnostic pitfall. We identified 9 cases of prostatic adenocarcinoma with aberrant positive GATA3 staining from 2015 to 2020 as part of a large consultation service at our institution. All 9 cases were grade group 5, 8 had a Gleason score of 5+5=10 and 1 had a score of 4+5=9. Five of the cases were from the prostate, 3 from the urinary bladder, and 1 from the prostatic urethra. All cases were morphologically typical of high-grade prostatic adenocarcinoma, although were sent for consultation due to uncertainty in the diagnosis. GATA3 positivity was strong, diffuse in 4 cases; strong, patchy in 2 cases and strong, focal in 3 cases. All cases were positive for NKX3.1, 6 positive for p501s, and 6 positive for PSA, with 7/9 cases showing expression of at least 2 prostate-specific markers. The current study describes that rare cases of prostatic adenocarcinoma can show focal or diffuse strong staining for GATA3. In order to avoid this diagnostic pitfall, undifferentiated carcinomas involving the prostate, bladder neck, or trigone should be evaluated not only with GATA3 but also prostate-specific markers.

Zebrafish keratocyte explant cultures as a wound healing model system: differential gene expression & morphological changes support epithelial-mesenchymal transition.

The control of collective cell migration of zebrafish keratocyte sheets in explant culture is of interest for cell migration and epithelial wound healing and depends on the gene expression profile. In a zebrafish genome array, ∼17.5% of the probe sets were differentially expressed greater than two-fold (p≤0.003) between 1 and 7 days of explant culture. Among the differentially expressed genes were a variety of wound healing-related genes and many of the biomarkers for epithelial-mesenchymal transition (EMT), including a switch from keratin and E-cadherin to vimentin and N-cadherin expression and several EMT-related transcription factors were found to be differentially expressed. Supporting evidence for EMT is seen in both morphological change and rearrangement of the actin cytoskeleton and in expression of cadherins during explant culture with a visible disassembly of the cell sheet. TGFß1 and TNFα expression were analyzed by qPCR at various time points and peak differential expression of both cytokines occurred at 3 days, indicating that the EMT process is ongoing under conditions routinely used in the study of fish keratocyte motility. These data establish that an EMT process is occurring during zebrafish keratocyte explant culture and support the use of this system as a wound healing model.