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

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.

Almási S ，Kuthi L ，Sejben A ，Vörös A ，Nagy Á ，Zombori T ，Cserni G ... -  《-》

Comparative expression of TRPS1, GATA3, SOX10, mammaglobin, and GCDFP-15 in effusion specimens with breast carcinoma.

Traditional immunohistochemistry (IHC) for breast carcinomas has shown low detection rates of metastatic breast carcinoma (MBC) in effusions. Although GATA3 has enhanced diagnostic accuracy in this realm, its limited utility in detecting triple-negative breast carcinoma (TNBC) has been highlighted. TRPS1 has been introduced as a potentially sensitive and specific marker in detecting MBC on histologic samples. We investigate the utility of TRPS1 as a marker for MBC in effusion specimens and compare its performance to SOX10, GATA3, mammaglobin (MG), and GCDFP-15. A database search identified malignant effusions involved by MBC between 2013 and 2021. Cases from unique patients with sufficient cellularity were evaluated for TRPS1, GATA3, SOX10, MG, and GCDFP-15 IHC. The intensity and extent of tumor cells (TC) were scored by two pathologists. Any discrepancies were jointly reviewed for consensus. GATA3 showed the highest rate of positivity (98.2%), followed by TRPS1 (89.5%), MG (43.9%), GCDFP-15 (21.1%), and SOX10 (3.5%). All GATA3-positive cases showed intermediate to high expression. Comparatively, TRPS1 showed more variability in staining extent and intensity. In 13 (22.8%) cases, TRPS1 showed extensive background staining of inflammatory and mesothelial cells. Of six TNBCs, GATA3, and TRPS1 were positive in six (100%) and four (66.7%) cases, respectively. While TRPS1 shows a lower detection rate for MBC than GATA-3, using a combination of these markers can enhance effusion cytology's performance in detecting MBC. However, variability in TRPS1 staining intensity and high background TRPS1 staining of inflammatory and mesothelial cells can increase difficulty in its evaluation.

Bradt A ，Jing X ，Smola BS ，Lew M ... -  《-》

TRPS1 is a promising marker for all subtypes of breast cancer.

Lui JW ，Tsang JY ，Li J ，Ko CW ，Tam F ，Loong TC ，Tse GM ... -  《-》

TRPS1, GATA3, and SOX10 expression in triple-negative breast carcinoma.

A diagnostic dilemma can be encountered when primary triple-negative breast carcinoma (TNBC) without an in situ component or metastatic TNBCs lose the currently used organ-specific marker such as GATA3, raising concerns about metastatic carcinoma from other sites. In the current study, we compared the newly identified breast marker TRPS1 with currently used breast markers GATA3 and SOX10 in whole-tissue sections from 315 cases of various subtypes of TNBC. TRPS1 was highly expressed in 100% of triple-negative primary and metastatic invasive lobular carcinomas, 99% of triple-negative primary and metastatic invasive breast carcinoma of no special type (IBC-NST), and 95% of metaplastic breast carcinomas. In contrast, GATA3 and SOX10 were expressed in 94% and 0% of invasive lobular carcinomas, 63% and 74% of IBC-NST, and 50% and 49% of metaplastic breast carcinomas, respectively. For special-type TNBCs, both TRPS1 and GATA3 were negative in acinic cell carcinomas, most cribriform adenoid cystic carcinomas, and neuroendocrine carcinomas, but positive in secretory carcinomas. Triple-negative apocrine carcinoma was the only subtype of TNBC with positive GATA3 but negative TRPS1. These data indicate that TRPS1 is a highly sensitive marker for TNBCs with positivity not only in GATA3/SOX10-positive TNBCs but also in almost all GATA3/SOX10-negative TNBCs.

Yoon EC ，Wang G ，Parkinson B ，Huo L ，Peng Y ，Wang J ，Salisbury T ，Wu Y ，Chen H ，Albarracin CT ，Resetkova E ，Middleton LP ，Krishnamurthy S ，Gan Q ，Sun H ，Huang X ，Shen T ，Chen W ，Parwani AV ，Sahin AA ，Li Z ，Ding Q ... -  《-》

Sry-related high-mobility-group/HMG box 10 (SOX10) as a sensitive marker for triple-negative breast cancer.

Confirmation of a breast origin for triple-negative breast cancer (TNBC) is sometimes problematic. The traditional breast markers GATA-binding protein 3 (GATA3), mammaglobin (MGB) and gross cystic disease fluid protein 15 (GCDFP15) have shown limitations in identifying TNBC. Here, we aimed to examine the diagnostic potential of the newly proposed TNBC marker, Sry-related high-mobility-group/HMG box 10 (SOX10). We analysed and compared SOX10 expression with GATA3, MGB and GCDFP15 expression in a test cohort of 1838 invasive breast cancers (IBCs) by using tissue microarrays. The findings from the test cohort were further examined with a validation cohort of 42 TNBCs in whole sections. The overall expression rates of SOX10, GATA3, MGB and GCDFP15 were 6.9%, 83.1%, 47.0%, and 34.8%, respectively. Among the TNBCs within this cohort, the expression rates of SOX10, GATA3, MGB and GCDFP15 were 31.3%, 34.5%, 27.9%, and 25.2%, respectively. SOX10 was strongly associated with TNBC (P < 0.001), whereas all other traditional markers were associated with non-TNBC (P < 0.001 for all). In addition, SOX10 was more correlated to basal-like breast cancer (BLBC) (P = 0.001) than five-marker-negative subtype among the TNBCs. A high expression rate of SOX10 (81%) was confirmed in the validation cohort. Additionally, SOX10 expression was inversely correlated with GATA3 and GCDFP15 expression, so they may complement each other in TNBC detection. The SOX10-GATA3 combination yielded a sensitivity of 60.3% for TNBC detection in the test cohort. SOX10 is a reliable marker for identifying TNBC, and complements GATA3. The SOX10-GATA3 combination may be used as a sensitive TNBC marker.

Jamidi SK ，Hu J ，Aphivatanasiri C ，Tsang JY ，Poon IK ，Li JJ ，Chan SK ，Cheung SY ，Tse GM ... -  《-》