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.

GATA3 and Mammaglobin are often used in the clinic to identify metastases of mammary origin due to their robust and diffuse expression in mammary tissue. However, the expression of these markers has not been well characterized in tumors from African American women. The goal of this study was to characterize and evaluate the expression of GATA3 and mammaglobin in breast tumors from African American women and determine their association with clinicopathological outcomes including breast cancer subtypes. Tissue microarrays (TMAs) were constructed from well preserved, morphologically representative tumors in archived formalin-fixed, paraffin-embedded (FFPE) surgical blocks from 202 patients with primary invasive ductal carcinoma. Mammaglobin and GATA3 expression was assessed using immunohistochemistry (IHC). Univariate analysis was carried out to determine the association between expression of GATA3, mammaglobin and clinicopathological characteristics. Kaplan-Meier estimates of overall survival and disease-free survival were also plotted and a log-rank test performed to compare estimates among groups. GATA3 expression showed statistically significant association with lower grade (p<0.001), ER-positivity (p<0.001), PR-positivity (p<0.001), and the luminal subtype (p<0.001). Mammaglobin expression was also significantly associated with lower grade (p=0.031), ER-positivity (p=0.007), and PR-positivity (p=0.022). There was no association with recurrence-free or overall survival. Our results confirm that GATA3 and mammaglobin demonstrate expression predominantly in luminal breast cancers from African American women. Additional markers with improved specificity and sensitivity are warranted for triple negative breast tumors given the high prevalence in women of African descent.

Introduction: Breast cancer (BC) diagnostics lack noninvasive methods and procedures for screening and monitoring disease dynamics. Admitted CellSearch® is used for fluid biopsy and capture of circulating tumor cells of only epithelial origin. Here we describe an RNA aptamer (MDA231) for detecting BC cells in clinical samples, including blood. The MDA231 aptamer was originally selected against triple-negative breast cancer cell line MDA-MB-231 using cell-SELEX. Methods: The aptamer structure in solution was predicted using mFold program and molecular dynamic simulations. The affinity and specificity of the evolved aptamers were evaluated by flow cytometry and laser scanning microscopy on clinical tissues from breast cancer patients. CTCs were isolated form the patients\' blood using the developed method of aptamer-based magnetic separation. Breast cancer origin of CTCs was confirmed by cytological, RT-qPCR and Immunocytochemical analyses. Results: MDA231 can specifically recognize breast cancer cells in surgically resected tissues from patients with different molecular subtypes: triple-negative, Luminal A, and Luminal B, but not in benign tumors, lung cancer, glial tumor and healthy epithelial from lungs and breast. This RNA aptamer can identify cancer cells in complex cellular environments, including tumor biopsies (e.g., tumor tissues vs. margins) and clinical blood samples (e.g., circulating tumor cells). Breast cancer origin of the aptamer-based magnetically separated CTCs has been proved by immunocytochemistry and mammaglobin mRNA expression. Discussion: We suggest a simple, minimally-invasive breast cancer diagnostic method based on non-epithelial MDA231 aptamer-specific magnetic isolation of circulating tumor cells. Isolated cells are intact and can be utilized for molecular diagnostics purposes.

Introduction. Triple negative breast carcinomas are characterized by a lack of hormone receptor and HER2 expression and inconsistent expression of breast-specific immunohistochemical markers. The expression of many site-specific markers in these tumors is largely unknown. The objective of the study was to examine the expression of widely used immunohistochemical markers on a large cohort of triple negative breast cancer. Methods. Sections from tissue microarrays were stained with 47 markers using routine protocols. Most markers were scored using a modified Allred method. ATRX, BAP1, SMAD4, e-cadherin, and beta-catenin were scored as retained or lost. Mammaglobin was considered positive if there was at least moderate intensity staining in any tumor cells. P16 was scored as overexpressed or not overexpressed; p53 was scored as wildtype, overexpressed, null, or cytoplasmic. Results. The cohort consisted of 639 tumors including 601 primary and 32 metastases. Overall, 96% expressed GATA3, mammaglobin, and/or SOX10 while 97% of no special type tumors expressed this panel. Carcinoma of apocrine differentiation demonstrated an AR positive, SOX10 negative, K5 negative/focal immunophenotype. PAX8 (SP348), WT1, Napsin A, and TTF1 (8G7G3/1) were never or rarely expressed while CA9, CDX2, NKX3.1, SATB2 (SATBA410), synaptophysin, and vimentin were variably expressed. Conclusions. Almost all TNBC express at least 1 of the 3 IHC markers: GATA3, mammaglobin, and/or SOX10. Carcinoma of apocrine differentiation is characterized by an AR positive, SOX10 negative, K5 negative or focal immunophenotype. Cautious interpretation of so-called site-specific markers, with knowledge of antibody clones, is required in excluding the diagnosis of triple negative breast cancer.

UNASSIGNED: Breast cancer (BC) plays a major public health in Egyptian woman. In Upper Egypt, there is an increase in incidence of BC compared to other Egyptian areas. Triple-negative BC, estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-neu-negative, is a high-risk BC that lacks the benefit of specific therapy that targets these proteins. Accurate determination of Caveolin-1(Cav-1), Caveolin-2 (Cav-2) and HER-2/neu status have become of major clinical significance in BC by focusing about its role as a tumor marker for response to different therapies.
UNASSIGNED: The present study was performed on 73 female BC patients in the South Egypt Cancer Institute. Blood samples were used for Cav-1, Cav-2, and HER-2/neu genes amplification and expression. In addition, immunohistological analysis of mammaglobin, GATA3, ER, PR, and HER-2/neu was done.
UNASSIGNED: There was a statistically significant association between Cav-1, 2 and HER-2/neu genes expression and the age of patients (P< 0.001). There are increase in the level of Cav-1, 2 and increase in HER-2/neu mRNA expression in groups treated with chemotherapy and group treated with both chemotherapy and radiotherapy compared to each group baseline level of genes mRNA expression before treatment. On the contrary, the group treated with chemotherapy, radiotherapy and hormonal therapy revealed increase on the level of Cav-1, 2 and HER-2/neu mRNA expression when compared with their baseline for the same patients before treatment.
UNASSIGNED: Noninvasive molecular biomarkers such as Cav-1 and Cav-2 have been proposed for use in the diagnosis and prognosis for women with BC.

Introduction  Breast cancer is the most common cancer in women in India and accounts for 14% of all cancers in women. Rise in mortality is due to lack of awareness and proper screening. Mammography and presently available serum biomarkers have low sensitivity and specificity. In our quest to identify a better biomarker, we studied mammaglobin (MAM) in patients with breast cancer and benign breast tumors. Aim  To evaluate serum mammaglobin in breast cancer patients and compare it with benign breast tumor patients and healthy controls. To compare it with existing biomarkers serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3). Materials and methods: This is a cross-sectional, case-control study of 77 subjects, of which 27 were breast cancer patients, 20 benign breast tumor patients, and 30 healthy controls. Serum CEA and CA15-3 were estimated by electrochemiluminescence immunoassay (ECLIA) and mammaglobin (MAM) by enzyme-linked immunosorbent assay (ELISA). Results  Mammaglobin and CEA levels were elevated in breast cancer patients, followed by benign breast tumors when compared with controls ( P  < 0.000001). Mammaglobin showed 81.5% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 88.9% negative predictive value (NPV). CEA showed 88.9% sensitivity, 82.5% specificity, 77.4% PPV, and 91.7% NPV. The area under the curve was the highest for MAM (0.892), followed by CEA (0.889) and CA 15-3 (0.555). CA15-3 showed poor diagnostic efficacy. Combined receiver operating characteristic (ROC) curve of the biomarkers MAM and CEA had an AUC of 0.913. Conclusion  Mammaglobin proved to be an efficacious biomarker in diagnosing breast cancer.

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.
CONCLUSIONS: 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.

OBJECTIVE: Secretory carcinoma (SC) (synonym: mammary analogue secretory carcinoma) is a low-grade salivary gland tumour that occurs in both major and minor salivary glands. SC is known for its wide morphological, architectural and immunohistochemical spectrum, which overlaps with those of several salivary gland neoplasms, including acinic cell carcinoma (AciCC) and intercalated duct-type intraductal carcinoma (IDC) in major salivary glands, and polymorphous adenocarcinoma (PAC) in minor salivary glands. These tumours share with SC some morphological features and SOX10 immunoreactivity; also, with the exception of AciCC, they all coexpress S100 and mammaglobin.
RESULTS: We compared MUC4 and mammaglobin expression in 125 salivary gland carcinomas (54 genetically confirmed SCs, 20 AciCCs, 21 PACs, and 30 IDCs) to evaluate the potential of these two markers to differentiate these entities. Moderate to strong diffuse MUC4 positivity was detected in 49 SCs (90.7%), as compared with none of the IDCs and PACs. In contrast, mammaglobin was frequently expressed in SCs (30 of 36 cases; 83.3%), IDCs (24/28; 85.7%), and PACs (7/19; 36.8%). Two of three high-grade SCs lost MUC4 expression in the high-grade tumour component. No significant correlation was found between MUC4 expression and the fusion variant in SC (ETV6-NTRK versus non-ETV6-NTRK).
CONCLUSIONS: The results of our study identify MUC4 as a sensitive (90.7%) and specific (100%) marker for SC, with high positive (100%) and negative (93.4%) predictive values. Thus, MUC4 may be used as a surrogate for SC in limited biopsy material and in cases with equivocal morphology.

Secretory carcinoma (SC) of the salivary gland was identified in 2010, and it is characterized by a specific ETV6 gene arrangement. The most common primary site for SC is the parotid gland; however, SC around the Stensen\'s duct is rare. Here we describe a rare case of a SC around the Stensen\'s duct that was initially misdiagnosed as a salivary duct cyst. A 59-year-old woman presented with a mass in the region of the left parotid papilla. Magnetic resonance imaging (MRI) revealed a well-circumscribed lesion and enhancement with a rim and an inner wall-like part that appeared in the late phase. Based on the initial clinical and imaging findings, a salivary duct cyst of the parotid gland was diagnosed. However, the lesion was histopathologically diagnosed as a SC based on immunohistochemical findings. The tumor cells showed diffuse positive staining for AE1/AE3, vimentin, and mammaglobin and focal positive staining for S-100 protein, SOX-10, and DOG-1. Fluorescence in-situ hybridization revealed ETV6 gene rearrangement in the tumor. In cases of cystic lesions around the Stensen\'s duct, clinicians should bear in mind that the possibility that they could be minor salivary gland cancers, such as SC.

OBJECTIVE: Non-small-cell lung cancer (NSCLC) and breast cancer are common entities. Staining for oestrogen receptor (ER), progesterone receptor (PgR), mammaglobin (MAMG) and GATA-binding protein 3 (GATA3) is frequently performed to confirm a mammary origin in the appropriate diagnostic setting. However, comprehensive data on the immunohistological expression of these markers in NSCLC are limited. Therefore, the aim of this study was to analyse a large cohort of NSCLCs and correlate the staining results with clinicopathological variables.
RESULTS: A tissue microarray was stained for ER, PgR, MAMG, human epidermal growth factor receptor 2 (HER2), and GATA3, and included 636 adenocarcinomas (ADCs), 536 squamous cell carcinomas (SqCCs), 65 large-cell-carcinomas, 34 pleomorphic carcinomas, and 20 large-cell neuroendocrine carcinomas. HER2 status was determined for immunohistochemically positive cases with chromogenic in-situ hybridisation. Markers with a proportion of ≥5% positive cases in ADC and SqCC were considered for survival analysis. Among ADCs, 62 (10%), 17 (3%), one (<1%), seven (1%), and 49 (8%) cases were positive for ER, PgR, MAMG, HER2, and GATA3, respectively. Among SqCCs, 10 (2%), 14 (3%), two (<1%) and 109 (20%) cases were positive for ER, PgR, HER2, and GATA3, but none of the samples showed positivity for MAMG. ER positivity was associated with ADC, female sex, smaller tumour size, and lower clinical stage. None of the markers had an impact on survival.
CONCLUSIONS: We report on ER, PgR, MAMG, HER2 and GATA3 expression in a large cohort of NSCLCs. Interpretation of these markers in the differential diagnostic setting should be based on a multimarker panel.