TRPS1

TRPS1 is a gene involved in Tricho-rhinophalangeal syndrome, an autosomal dominant skeletal disorder. TRPS1 encodes a GATA-type transcription factor that has nine zinc-finger motifs. TRPS1 is localized in human chromosome 8q23–24. TRPS1 is expressed in a tissue-specific manner and acts as a critical regulator of organ development. TRPS1 regulates several major cellular processes as e.g.  bone, breast and hair development. High TRPS1 protein expression is observed in epithelial cells of breast glands, sebaceous glands, hair follicles and uterine endometrium/endocervix. Lower expression is seen in many stromal cells, germ cells in testis and squamous epithelial cells of esophagus.

IHC for TRPS1 is typically used to identify breast carcinomas including triple negative breast carcinomas in the diagnostic work-up of carcinomas of unknown primary origin. IHC for TRPS is reported to have an increased diagnostic sensitivity for breast carcinomas compared to established markers as GATA3, GCDFP15 and SOX10. TRPS1 is also expressed in many non-breast neoplasias as gynecological carcinomas, NSCLCs, prostate adenocarcinomas and urothelial carcinomas. The TRPS1 expression in breast carcinomas is typically extensive whereas a reduced expression is most frequently observed in non-breast neoplasias.

Breast hyperplasia, uterine cervix and appendix/colon is at present recommended as positive and negative tissue controls. Virtually all luminal epithelial cells in breast hyperplasia should show a moderate to strong nuclear staining reaction. In uterine cervix, most suprabasal squamous epithelial cells and dispersed stromal cells should display an at least weak to moderate nuclear staining reaction. No staining should be seen in epithelial cells in appendix/colon. A weak to moderate, distinct nuclear staining reaction might be seen in ganglion cells and scattered lymphocytes in appendix. Smooth muscle cells should be negative or “as weak as possible”.