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Histopathology Apr 2024Trichorhinophalangeal syndrome-1 (TRPS1) has been proposed as a novel breast marker with equally high expression in breast cancer (BC) subtypes, making it a useful...
AIMS
Trichorhinophalangeal syndrome-1 (TRPS1) has been proposed as a novel breast marker with equally high expression in breast cancer (BC) subtypes, making it a useful diagnostic tool. Here, its expression was evaluated alongside other commonly used markers [GATA3, GCDFP15, mammaglobin (MGB) and SOX10] in a large cohort of BCs (n = 1852) and their corresponding nodal metastases. Its usefulness as a diagnostic tool and its correlation with clinicopathological features were assessed.
METHODS AND RESULTS
TRPS1 was expressed at 75.8% overall in the BC cohort, with at least 58% expression among BC subtypes. It was less sensitive than GATA3 for luminal and HER2-overexpressing (HER2-OE) cancers (luminal A: 82 versus 97%; luminal B: 80 versus 95%; HER2-OE: 62 versus 76%), but it was the most sensitive for TNBC (60 versus ≤ 41%). It showed a stable expression in nodal metastases (primary tumour 76 versus nodal metastasis 78%), unlike a reduced nodal expression for GATA3 (86 versus 77%). TRPS1 outperformed GATA3 in detecting non-luminal cancers when paired with other breast markers. TRPS1 and GCDFP15 was the most sensitive combination in TNBC detection, with a 76% detection rate. For TRPS1-negative and GCDFP15-negative TNBCs, SOX10 was more sensitive than GATA3 (29 versus 24%).
CONCLUSIONS
TRPS1 is a highly sensitive marker for all breast cancer subtypes, outperforming GATA3 in non-luminal cancers and displaying the highest sensitivity for TNBC detection when combined with GCDFP15. It is a valuable addition to the breast marker panel for accurate identification of BC.
Topics: Humans; Female; Breast Neoplasms; Triple Negative Breast Neoplasms; Biomarkers, Tumor; Carrier Proteins; Mammaglobin A; Breast; GATA3 Transcription Factor; Repressor Proteins
PubMed: 38173281
DOI: 10.1111/his.15126 -
Annals of Diagnostic Pathology Dec 2023Salivary gland tumors are diverse in morphology and both benign and malignant tumors may pose diagnostic challenges especially in small biopsies. Secretory carcinoma...
Salivary gland tumors are diverse in morphology and both benign and malignant tumors may pose diagnostic challenges especially in small biopsies. Secretory carcinoma (SC) is histologically characterized by microcysts, follicles, solid growth pattern and occasional papillary structures, and absence of zymogen granules. SC is molecularly defined by the presence of novel gene fusion ETV6::NTRK3. Among the positive stains (S100 and mammaglobin), MUC4 is now another promising marker for the diagnosis of SC, that would enable the pathologists to exclude other morphologically close simulators. Aim of this study was to report clinicopathological features and assess utility of MUC4 in the diagnosis of SC. MUC4 was performed on 22 cases of SC. Glass slides were reviewed to record morphological patterns and staining of S100, mammaglobin, DOG1 and MUC4. Age ranged from 9 to 63 years with mean age of 34.41 ± 16.28 years. The male: female ratio was 72.7 %:27.3 %. The majority occurred in major salivary glands. A combination of patterns was seen; microfollicles were the most prevalent (90 %) followed by papillary-cystic and macrofollicles. MUC4 was positive in 19/21 (90 %) cases with almost equal number of 2+ and 3+ staining. MUC4 was negative in all cases of acinic cell carcinoma, polymorphous adenocarcinoma, adenoid cystic carcinoma, salivary duct carcinoma, myopepithelioma and myoeithelial carcinoma, cystadenoma and cribriform adenocarcinoma and all except 3 cases of mucoepidermoid carcinoma tested. Overall sensitivity of MUC4 was 95.4 %, specificity 90 %, p-value being <0.01, positive predictive value 87.5 % and negative predictive value 96.4 %. A characteristic cytoplasmic granular pattern was observed in 76.1 % tumors. S100 and mammaglobin were positive in all the performed cases. DOG1 was positive in 6/11 (28.5 %) tumors. In conclusion, MUC4 is a useful addition to a diagnostic immunohistochemical panel for SC, and to distinguish it from close potential mimickers such as acinic cell carcinoma, especially in practice settings where molecular testing is unavailable.
Topics: Humans; Male; Female; Adolescent; Young Adult; Adult; Middle Aged; Child; Biomarkers, Tumor; Carcinoma, Acinar Cell; Immunohistochemistry; Salivary Glands; Carcinoma; Salivary Gland Neoplasms; Mammaglobin A; Carrier Proteins; Mucin-4
PubMed: 37924657
DOI: 10.1016/j.anndiagpath.2023.152220 -
International Journal of Molecular... Aug 2023The continuous evolution of cancer biology has led to the discovery of mammaglobin, a potential novel biomarker for breast carcinoma. This review aims to unravel the... (Review)
Review
The continuous evolution of cancer biology has led to the discovery of mammaglobin, a potential novel biomarker for breast carcinoma. This review aims to unravel the enigmatic aspects of mammaglobin and elucidate its potential role in redefining the paradigm of breast carcinoma biomarkers. We will thoroughly examine its expression in tumoral and peritumoral tissues and its circulating levels in the blood, thereby providing insights into its possible function in cancer progression and metastasis. Furthermore, the potential application of mammaglobin as a non-invasive diagnostic tool and a target for personalized treatment strategies will be discussed. Given the increasing incidence of breast carcinoma worldwide, the exploration of novel biomarkers such as mammaglobin is crucial in advancing our diagnostic capabilities and treatment modalities, ultimately contributing to improved patient outcomes.
Topics: Humans; Female; Breast Neoplasms; Biomarkers; Biology
PubMed: 37686210
DOI: 10.3390/ijms241713407 -
Diagnostic Cytopathology Nov 2023Traditional immunohistochemistry (IHC) for breast carcinomas has shown low detection rates of metastatic breast carcinoma (MBC) in effusions. Although GATA3 has enhanced... (Comparative Study)
Comparative Study
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
Topics: Female; Humans; Biomarkers, Tumor; Breast Neoplasms; Carrier Proteins; GATA3 Transcription Factor; Immunohistochemistry; Mammaglobin A; Repressor Proteins; SOXE Transcription Factors; Triple Negative Breast Neoplasms
PubMed: 37461248
DOI: 10.1002/dc.25195