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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 -
Virchows Archiv : An International... May 2023The lack of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 expression in breast cancer (BC) is the basis for the categorization...
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.
Topics: Humans; Female; Triple Negative Breast Neoplasms; Biomarkers, Tumor; Breast Neoplasms; Keratin-5; Reproducibility of Results; Mammaglobin A; Carrier Proteins; GATA3 Transcription Factor; Repressor Proteins
PubMed: 37012444
DOI: 10.1007/s00428-023-03535-4 -
Diagnostics (Basel, Switzerland) Mar 2023Human mammaglobin-A (SCGB2A2) is a secretory protein with an unknown function that is used as a diagnostic marker for breast cancer. However, other tumors can also...
Human mammaglobin-A (SCGB2A2) is a secretory protein with an unknown function that is used as a diagnostic marker for breast cancer. However, other tumors can also express mammaglobin-A. To comprehensively study patterns of mammaglobin-A expression, a tissue microarray containing 16,328 samples from 128 different tumor types as well as 608 samples of 76 different normal tissue types was analyzed using immunohistochemistry. Mammaglobin-A positivity was found in only a few normal tissues, including luminal cells of the breast as well as endocervical and endometrial glands. In tumor tissues, 37 of 128 tumor categories showed mamma-globin-A staining, 32 of which were derived from one of four organs: breast (6 tumor categories), endometrium (5 tumor categories), ovary (5 tumor categories), and salivary glands (16 tumor categories). Only five additional tumor types showed occasional weak mammaglobin positivity, including medullary thyroid cancer, teratoma of the testis, squamous cell carcinoma of the skin and pharynx, and prostatic adenocarcinoma. Among 1139 evaluable invasive breast carcinomas of no special type, low mammaglobin-A immunostaining was linked to high BRE grade ( = 0.0011), loss of estrogen and progesterone receptor expression ( < 0.0001 each), and triple-negative status ( < 0.0001) but not to patient survival. In endometrial cancer, mammaglobin-A loss was linked to an advanced tumor stage ( = 0.0198). Our data characterize mammaglobin-A as a highly specific marker for tumors derived from either the breast, female genitals, or salivary gland.
PubMed: 36980510
DOI: 10.3390/diagnostics13061202 -
Asian Pacific Journal of Cancer... Feb 2023Mammaglobin and GCDFP-15 are traditional immunohistochemistry (IHC) markers utilized to recognize metastasis of breast carcinoma in an unknown primary. GATA-3 is...
BACKGROUND AND OBJECTIVE
Mammaglobin and GCDFP-15 are traditional immunohistochemistry (IHC) markers utilized to recognize metastasis of breast carcinoma in an unknown primary. GATA-3 is increasingly being used as a marker of primary breast origin. This study was done to evaluate and compare GATA-3 with GCDFP-15 and Mammaglobin in invasive primary including metastatic and triple negative breast carcinomas.
METHODS
Immunohistochemistry for GATA-3, GCDFP-15 and Mammaglobin was applied on 100 cases of primary breast carcinomas, including 20 triple negative cases and 30 cases of metastatic breast carcinomas. Staining scores were given for each marker by multiplying the percentage of positive tumor cells by the intensity of staining (1+, 2+ or 3+), with scores ranging from 0 to 300. Staining score of 1 or more was considered positive.
RESULTS
GATA-3 was expressed in 92% of primary, 80% of metastatic and 60% of triple negative breast carcinomas, with an average staining score of 270. Mammaglobin was expressed in 68% of primary, 56.6% of metastatic and 25% of triple negative breast carcinomas, with an average staining score of 180. GCDFP-15 was expressed in 48% of primary, 26.6% of metastatic and 05% of breast carcinomas, with an average staining score of 60. GATA-3 demonstrated to have higher staining score (average of 270) than other two markers in maximum number of cases.
CONCLUSION
GATA-3 has a higher sensitivity and increased staining scores in primary breast carcinomas, metastatic breast carcinomas as well as in triple negative breast carcinomas.
Topics: Humans; Asian People; Breast; Staining and Labeling; Triple Negative Breast Neoplasms; Mammaglobin A; Biomarkers, Tumor
PubMed: 36853299
DOI: 10.31557/APJCP.2023.24.2.509 -
Breast Cancer Research : BCR Oct 2022Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and...
BACKGROUND
Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and documented clinical history, sensitive and specific immunohistochemical (IHC) markers such as GCDFP-15, mammaglobin, and GATA3 are helpful for determining breast origin. However, these markers are reported to show lower sensitivity in certain subtypes, such as triple-negative breast cancer (TNBC).
MATERIALS AND METHODS
Using bioinformatics analyses, we identified a potential diagnostic panel to determine breast origin: matrix Gla protein (MGP), transcriptional repressor GATA binding 1 (TRPS1), and GATA-binding protein 3 (GATA3). We compared MGP, TRPS1, and GATA3 expression in different subtypes of breast carcinoma of (n = 1201) using IHC. As a newly identified marker, MGP expression was also evaluated in solid tumors (n = 2384) and normal tissues (n = 1351) from different organs.
RESULTS
MGP and TRPS1 had comparable positive expression in HER2-positive (91.2% vs. 92.0%, p = 0.79) and TNBC subtypes (87.3% vs. 91.2%, p = 0.18). GATA3 expression was lower than MGP (p < 0.001) or TRPS1 (p < 0.001), especially in HER2-positive (77.0%, p < 0.001) and TNBC (43.3%, p < 0.001) subtypes. TRPS1 had the highest positivity rate (97.9%) in metaplastic TNBCs, followed by MGP (88.6%), while only 47.1% of metaplastic TNBCs were positive for GATA3. When using MGP, GATA3, and TRPS1 as a novel IHC panel, 93.0% of breast carcinomas were positive for at least two markers, and only 9 cases were negative for all three markers. MGP was detected in 36 cases (3.0%) that were negative for both GATA3 and TRPS1. MGP showed mild-to-moderate positive expression in normal hepatocytes, renal tubules, as well as 31.1% (99/318) of hepatocellular carcinomas. Rare cases (0.6-5%) had focal MGP expression in renal, ovarian, lung, urothelial, and cholangiocarcinomas.
CONCLUSIONS
Our findings suggest that MGP is a newly identified sensitive IHC marker to support breast origin. MGP, TRPS1, and GATA3 could be applied as a reliable diagnostic panel to determine breast origin in clinical practice.
Topics: Female; Humans; Triple Negative Breast Neoplasms; Breast Neoplasms; Biomarkers, Tumor; GATA3 Transcription Factor; Mammaglobin A; Calcium-Binding Proteins; Repressor Proteins; Matrix Gla Protein
PubMed: 36284362
DOI: 10.1186/s13058-022-01569-1 -
FEBS Open Bio Oct 2022Overexpression of human epidermal growth factor receptor 2 (HER2) in various cancers is correlated with poor patient survival. Trastuzumab, a recombinant humanized...
Overexpression of human epidermal growth factor receptor 2 (HER2) in various cancers is correlated with poor patient survival. Trastuzumab, a recombinant humanized monoclonal antibody against HER2, has been considered to be a first-line therapy for HER2-positive breast cancer patients, but its usefulness is limited by the development of resistance. In this study, we established resistant cells by long-term treatment with trastuzumab. These cells showed higher proliferation, invasion, and migration abilities than the wild-type cells. Mammaglobin 1 (MGB1), cyclin D1, E1, A2, and phosphorylated NF-κB (p-p65) were upregulated in resistant cells. These proteins regulate cell proliferation, migration, and invasion of resistant cells. Depletion of MGB1 decreased cyclin and p-p65 expression. Cyclin D1 and A2, but not E1 expression, were affected by p-p65 downregulation. In summary, our results indicate that MGB1 expression is increased in breast cancer cells that have gained resistance to trastuzumab, and suggest that MGB1 promotes aggressiveness through cyclin and NF-κB regulation.
Topics: Breast Neoplasms; Cell Line, Tumor; Cyclin D1; Female; Humans; Mammaglobin A; NF-kappa B; Trastuzumab
PubMed: 35945910
DOI: 10.1002/2211-5463.13468 -
Seminars in Diagnostic Pathology Sep 2022Due to the high prevalence of breast cancer in the female, a metastasis from primary breast cancer is usually considered in the differential diagnosis of metastatic... (Review)
Review
Due to the high prevalence of breast cancer in the female, a metastasis from primary breast cancer is usually considered in the differential diagnosis of metastatic carcinoma in the female patient, even for those without a history of breast cancer, as some breast cancers are first diagnosed as metastases. Immunohistochemical analysis for breast cancer markers is the most common way to determine breast cancer origin besides clinical history and histology. In this review, we (1) summarize the commonly used and the newly identified breast cancer markers, including GCDFP-15, mammaglobin, GATA3, SOX10, and TRPS1; (2) point out the strengths and weaknesses of using these markers for breast cancers with luminal/epithelial or basal/myoepithelial differentiation; and (3) recommend diagnostic panels to differentiate breast carcinoma from carcinoma with similar morphology of other origins.
Topics: Biomarkers, Tumor; Breast Neoplasms; Carcinoma; Female; Humans; Immunohistochemistry; Mammaglobin A; Repressor Proteins
PubMed: 35461734
DOI: 10.1053/j.semdp.2022.04.002