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Author Spotlight: High-Sensitivity Tissue Factor Activity Assay for Plasma Diagnosis
Published on: December 29, 2023
The Diagnostic Role of TFF1, TFF3, FOXA1, CA XII and TRPS1 in Serous Effusions
Ben Davidson1,2, Arild Holth1, Jeremias Wohlschlaeger3,4
1Department of Pathology, Oslo University Hospital, Norwegian Radium Hospital, Oslo, Norway.
Insights
Trefoil factor-1 and -3 (TFF1, TFF3), FOXA1, CA XII, and TRPS1 are sensitive diagnostic markers for breast carcinoma in effusions. FOXA1 showed the highest sensitivity, while TRPS1 was the most specific marker.
Area of Science:
- Oncology
- Pathology
- Biomarker Discovery
Background:
- Serous effusions are challenging for cancer diagnosis.
- Identifying reliable diagnostic and prognostic markers for breast carcinoma in effusions is crucial.
Purpose of the Study:
- To evaluate the diagnostic utility of trefoil factor-1 and -3 (TFF1, TFF3), forkhead box protein A1 (FOXA1), carbonic anhydrase XII (CA XII), and trichorhinophalangeal syndrome type 1 (TRPS1) in serous effusions.
- To investigate the prognostic role of these markers in breast carcinoma.
Main Methods:
- Immunohistochemistry was used to analyze protein expression in 247 effusions.
- The study included various carcinomas (breast, tubo-ovarian, lung, gastrointestinal, etc.) and mesotheliomas.
Main Results:
- TFF1, TFF3, FOXA1, CA XII, and TRPS1 were expressed in 67%, 70%, 88%, 82%, and 83% of breast carcinomas, respectively.
- All markers were significantly overexpressed in breast carcinoma compared to tubo-ovarian and lung carcinomas.
- TFF1, TFF3, and FOXA1 expression was higher in receptor-positive breast carcinomas; TFF1 showed a trend towards longer survival.
Conclusions:
- TFF1, TFF3, FOXA1, CA XII, and TRPS1 are sensitive markers for breast carcinoma in effusions.
- FOXA1 demonstrated the highest sensitivity, and TRPS1 exhibited the highest specificity.
- Further research is needed to confirm the prognostic value of these markers in breast carcinoma effusions.
Objective:
To analyse the diagnostic role of trefoil factor-1 and -3 (TFF1, TFF3), forkhead box protein A1 (FOXA1), carbonic anhydrase XII (CA XII) and trichorhinophalangeal syndrome type 1 (TRPS1) in serous effusions. The prognostic role of these markers in breast carcinoma was additionally studied.
Methods:
Protein expression by immunohistochemistry was analysed in 247 effusions, consisting of 60 breast carcinomas, 54 tubo-ovarian carcinomas, 47 mesotheliomas, 44 lung carcinomas, 20 uterine corpus and cervical carcinomas, 17 gastrointestinal carcinomas and 5 cancers of other origin.
Results:
TFF1, TFF3, FOXA1, CA XII and TRPS1 expression was found in 67%, 70%, 88%, 82% and 83% of breast carcinomas, respectively. Expression of all markers was seen in some carcinomas of other origin, most commonly in GI metastases, but was least frequent for TRPS1. CA XII expression was additionally seen in mesotheliomas and reactive mesothelial cells. All 5 markers were significantly overexpressed in breast compared to tubo-ovarian carcinoma (all p < 0.001) and lung carcinoma (all p < 0.001 except for FOXA1, p = 0.023). TFF1 (p = 0.003), TFF3 (p = 0.008) and FOXA1 (p = 0.017) expression was significantly higher in receptor-positive compared to receptor-negative primary breast carcinomas. In survival analysis for 44 breast carcinoma patients with clinical data, TFF1 expression was associated with a trend for longer overall (p = 0.096) and disease-free (p = 0.06) survival.
Conclusion:
TFF1, TFF3, FOXA1, CA XII and TRPS1 are sensitive breast carcinoma markers, with FOXA1 performing best in terms of sensitivity and TRPS1 being the most specific. Whether the expression of these markers in breast carcinoma effusions is informative of survival merits further research.

