Expression of Gata Binding Protein 3 as a Prognostic Factor in Urogenital Lesions and Its Association With Morphology

Abstract

Background: Urogenital malignancies, encompassing urinary bladder cancer, prostate cancer, and renal cell carcinoma, pose significant diagnostic challenges due to overlapping histopathological features. GATA binding protein 3 (GATA3), a transcription factor associated with urothelial tissue, has shown promise as a potential diagnostic marker. This study aimed to investigate the incidence of these malignancies, explore GATA3's involvement in urothelial cancer (UC), and determine its role in distinguishing urogenital malignancies.

Materials and methods: A cross-sectional, retro-prospective, hospital-based study was conducted from May 2019 to April 2021. The surgical samples of patients who underwent transurethral resection of bladder tumour (TURBT), transurethral resection of the prostate (TURP), radical cystoprostatectomy, total and partial radical nephrectomy specimens during the study period were reviewed. Patients diagnosed with urinary bladder neoplasm and high-grade prostate neoplasm along with chromophobe, oncocytic, sarcomatoid variant and clear cell carcinoma, renal cell carcinoma were included. Immunohistochemical analysis of GATA3 expression was performed, with scoring based on nuclear staining intensity and percentage of tumor cells labeled.

Results: The study included 64 patients, predominantly males over 60 years. Personal habits revealed a high prevalence of smoking (85.9%). The most prevalent symptom was hematuria (75.0%), followed by hematuria with urgency (20.3%). The most common site of lesion was posterolateral (31.3%). Urothelial cancer was the most common malignancy, primarily high-grade. Strong positive GATA3 expression was significantly associated with high-grade UC (p=0.01) and invasion (p=0.01). However, low-grade UC and papillary urothelial neoplasm of low malignant potential exhibited moderate GATA3 expression. GATA3 demonstrated potential for distinguishing UC from other histological types.

Conclusion: GATA3 expression correlates with high-grade urothelial cancer and invasive behavior, suggesting its utility as a diagnostic marker in challenging cases.

Keywords: gata3; histopathology; immunohistochemistry; prostate cancer; renal cell carcinoma; urothelial carcinoma.

Figure 1. Morphological characteristics and GATA3 expression in the tumour with papillary and congested blood vessels in the lamina propria

(1a) Photomicrograph shows a tumour with papillary structures and congested blood vessels in the lamina propria (H&E,10x); (1b) The image shows transitional cells exhibiting moderate to marked pleomorphism with overcrowding and loss of polarity. The cells have round to oval enlarged conspicuous hyperchromatic nuclei, conspicuous nucleoli, and moderate amounts of cytoplasm. Increased mitotic activity is seen at different levels of stratification (H&E,40x); (1c) shows strong nuclear positivity.

Figure 2. Morphological characteristics and GATA3 expression in LGUC

LGUC, low-grade urothelial cancer; GATA3, GATA binding protein 3 (2a, 2b) The image shows an increased cell layer, predominantly ordered architectural pattern of fused papillae showing moderate pleomorphism, (LGUC) (H&E, 10x & 40x); (2c, 2d) (GATA3) showing strongly positive (H&E, 10x & 40x); (2e) the image shows cells exhibiting moderate to marked pleomorphism with overcrowding and loss of polarity. The cells have round to oval enlarged conspicuous hyperchromatic nuclei, conspicuous nucleoli, and moderate amounts of cytoplasm (H&E,40x); (2f) (GATA3) showing strongly positive (H&E,40x).

Figure 3. Morphological characteristics and GATA3 expression in HGUC invading lamina propria and muscularis propria

GATA3, GATA binding protein 3; HGUC, high-grade urothelial cancer. (3a) Photomicrograph of HGUC shows neoplastic cells invading into lamina propria (H&E, 40x); (3b) (GATA3): Shows strongly positive (H&E, 40x); (3c) Photomicrograph of HGUC shows a neoplastic cell invading into muscularis propria (H&E, 10x); (3d, 3e) (GATA3) shows strongly positive (H&E, 10x & 40x).

Figure 4. Necrosis and GATA3 expression in tumour microenvironment

GATA3, GATA binding protein. (4a, 4b) (HPE & GATA3, 40x & 40x) shows necrosis and moderately positive.

Figure 5. HGUC with squamous, neuroendocrine, and sarcomatous and subsequent GATA3 expression

GATA-3, GATA binding protein 3; HGUC, high-grade urothelial cancer. (5a) HGUC with squamous differentiation; (5b) GATA3 shows moderately positive; (5c) HGUC with neuroendocrine differentiation; (5d) GATA3 shows negative; (5e) HGUC with sarcomatous differentiation; (5f) GATA3 shows negative.

Figure 6. Morphological characteristics and GATA3 expression in chromophobe renal cell carcinoma

GATA-3, GATA binding protein 3. (6a) Photomicrograph showing tumor cell arranged in sheets, comprised of polygonal to ovoid with well-delineated margins, small nuclei with conspicuous nucleoli, and abundant granular eosinophilic cytoplasm and infrequent mitotic figures (chromophobe renal cell carcinoma, H&E, 40x); (6b) (GATA3, 40x) Negative.

Figure 7. Ductal adenocarcinoma histopathology and GATA3 expression

GATA3, GATA binding protein 3. (7a) Photomicrograph showing tumour cells arranged in a glandular and ductal pattern showing moderate pleomorphism, conspicuous nucleoli, moderate cytoplasm, and increased mitosis (ductal adenocarcinoma, H&E, 40x); (7b) (GATA3, 40x) Negative.