Diagnostic Utility of TRPS1 Immunohistochemistry in Primary and Metastatic Breast Carcinoma with Special Emphasis on Spindle Cell Neoplasms of the Breast

Introduction

Breast cancer, a major contributor to cancer-related deaths in females, presents significant challenges in classification and diagnosis, particularly triple negative breast cancers (TNBC). This study explores the utility of Trichorhinophalangeal syndrome type 1 (TRPS1) as a novel biomarker, comparing its efficacy with GATA3 in TNBC with a specific focus on spindle cell neoplasms.

Methods

Our pathology database was searched to identify breast carcinoma cases between January 2021 and July 2021. All cases of poorly differentiated breast carcinoma (primary and metastatic) and primary spindle cell neoplasms of breast confirmed on core biopsies, in women greater than 18 years were selected. Immunohistochemical staining for ER, PR, HER2, GATA3 and TRPS1 were interpreted by two pathologists. TRPS1 and GATA3 expression levels among different groups were analyzed.

Results

Our study cohort comprised of 60 cases (24 primary breast carcinomas, 22 metastatic breast carcinomas and 14 spindle cell lesions of the breast). Our study revealed TRPS1’s superior sensitivity in TNBC, with 84% positivity compared to 53% for GATA3. TRPS1 showed promise in diagnosing spindle cell neoplasms, identifying 6/14 (43%) of cases, while GATA3 yielded no positive results. The six spindle cell cases that were TRPS1 positive were one synovial sarcoma, two malignant phyllodes, one fibromatosis, one myofibroblastoma and one angiosarcoma.

Conclusion

TRPS1 holds substantial promise as a sensitive and novel diagnostic marker for TNBC in comparison to GATA3. The differential diagnostic utility of TRPS1 warrants careful consideration due to its positivity in other spindle cell neoplasms of the breast, which may present as differential diagnoses for metaplastic carcinoma.

Highlights

• TRPS1 demonstrated superior sensitivity (84%) compared to GATA3 (53%) in identifying triple-negative breast carcinomas (TNBC), supporting its role as a promising diagnostic marker.

• TRPS1, unlike GATA3, showed positivity in 43% of spindle cell breast neoplasms, including malignant phyllodes, fibromatosis, myofibroblastoma, angiosarcoma, and synovial sarcoma, highlighting its broader expression spectrum.

• Pathologists should exercise caution in interpreting TRPS1 positivity within spindle cell lesions, as its expression may mimic metaplastic carcinoma, underscoring the need for careful correlation with morphology and other markers.