Paired Immunohistochemical Evaluation of TRPS1 and GATA3 in Triple-Negative Breast Carcinoma: A Multi-Institutional Series from Iraq

Abstract

Background: TRPS1 is an emerging nuclear marker of breast lineage that may retain expression in triple-negative breast carcinoma (TNBC), in which GATA3 expression can be absent. This study compared TRPS1 and GATA3 expression within the same TNBC specimens and examined their associations with clinicopathologic characteristics. Methods: This retrospective cross-sectional study included 30 formalin-fixed, paraffin-embedded TNBC specimens selected from 40 cases screened at three pathology units in Karbala, Iraq, between January 2023 and December 2024. Triple-negative status was obtained from the original diagnostic pathology records and was required for eligibility. Whole-tissue sections were immunostained for TRPS1 (clone EP392) and GATA3 (clone L50-823). Nuclear staining extent and intensity were multiplied to generate an immunoreactivity score, with a score ≥2 considered positive. Wilson 95% confidence intervals (CIs), the two-sided exact McNemar test, Fisher’s exact test, and the Benjamini–Hochberg correction were applied. Results: TRPS1 was positive in 28 of 30 tumors (93.3%; 95% CI, 78.7%–98.2%), whereas GATA3 was positive in 22 of 30 tumors (73.3%; 95% CI, 55.6%–85.8%). Twenty-one tumors were positive for both markers, seven were TRPS1-positive/GATA3-negative, one was TRPS1-negative/GATA3-positive, and one was negative for both markers. The observed positivity rate was 20.0 percentage points higher for TRPS1 than for GATA3; however, the exact paired comparison did not reach the conventional threshold for statistical significance (P = 0.070). At least one marker was positive in 29 of 30 tumors (96.7%; 95% CI, 83.3%–99.4%). High expression was observed in 22 tumors for TRPS1 and 14 tumors for GATA3. No association with clinicopathologic characteristics remained statistically significant after adjustment for multiple comparisons. Conclusions: TRPS1 showed a higher observed positivity rate than GATA3 and identified seven of the eight GATA3-negative TNBCs. The single GATA3-positive/TRPS1-negative case suggests that these markers may be complementary rather than interchangeable. In diagnostically challenging TNBC cases, TRPS1 may strengthen a breast-lineage immunohistochemical panel when interpreted alongside morphology, clinical context, and site-directed markers.