TRPS1 expression in cytokeratin 5 expressing triple negative breast cancers, its value as a marker of breast origin

Abstract

The lack of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression in breast cancer (BC) is the basis for the categorization of the tumour as triple negative breast carcinoma (TNBC). The majority of TNBCs are aggressive tumours with common metastases and decreased expression of markers that could help in identifying the metastatic lesion as of mammary origin. Breast markers, such as gross cystic disease fluid protein-15 (GCDPF-15), GATA binding protein 3 (GATA3), mammaglobin (MGB) and SOX10, are not uniquely specific to BC. Our aim was to evaluate trichorhinophalangeal syndrome type 1 (TRPS1) protein as a breast marker in a series of cytokeratin-5-expressing TNBC, mostly corresponding to basal-like TNBCs, previously characterized for the expression of other breast markers. One hundred seventeen TNBCs in tissue microarrays were immunostained for TRPS1. The cut-off for positivity was ≥ 10%. The reproducibility of this classification was also assessed. TRPS1 positivity was detected in 92/117 (79%) cases, and this exceeded the expression of previously tested markers like SOX10 82 (70%), GATA3 11 (9%), MGB 10 (9%) and GCDFP-15 7 (6%). Of the 25 TRPS1-negative cases, 11 were positive with SOX10, whereas 5 to 6 dual negatives displayed positivity for the other makers. The evaluation showed substantial agreement. Of the five markers compared, TRPS1 seems the most sensitive marker for the mammary origin of CK5-expressing TNBCs. Cases that are negative are most often labelled with SOX10, and the remainder may still demonstrate positivity for any of the 3 other markers. TRPS1 has a place in breast marker panels.

TRPS1 is a Highly Sensitive Marker for Breast Cancer

“…Other studies have reported 79% to 91% TRPS1 positivity in triple-negative breast cancer. 10 , 26 , 38 , 39 These figures are again higher than the 43% to 56% positivity rates described for GATA3 in these tumors. 10 , 26 , 27 …”

TRPS1 expression in breast angiosarcoma

“…A promising alternative is TRPS1, which has garnered attention due to its widespread expression, regardless of hormone receptor status, making it a versatile marker in breast carcinoma diagnostics [10,14]. Our group reinforced the value of TRPS1 expression in breast carcinomas with a triple-negative phenotype [15]. On the other hand, it is crucial to acknowledge that there are limited data available regarding TRPS1 positivity in other tumor types.…”

“…Positive immunohistochemical reactions were considered when at least 10% of tumor cells displayed labeling at any staining intensity. This threshold had been previously established by our group in testing TRPS1 expression in breast carcinomas [15], aligning with the approach used by the group of Wang and colleagues [13]. Notably, we categorized a case as either positive or negative for TRPS1 only when there was unanimous agreement among the readers.…”

“…In contrast, breast carcinoma is marked by elevated TRPS1 expression, underscoring its significance in carcinogenesis and tumor cell survival [14]. Notably, TRPS1 staining is observed in both hormone receptor-positive and triple-negative breast cancers, making it an attractive immunohistochemical marker in diagnostic work [15,16]. Limited data exist regarding TRPS1 positivity in other primary breast neoplasms.…”

A Case of Esophageal Adenocarcinoma Metastatic to the Breast

“…TRPS1 (trichorhinophalangeal syndrome type 1) serves as a transcriptional repressor protein that demonstrates a robust indication of primary breast cancer origin [ 11 ]. While GATA3 exhibits high sensitivity in identifying tumors of primary breast origin, its sensitivity when it comes to pinpointing triple-negative breast cancers as originating from the breast is lower [ 12 ].…”