Mammaglobin Expression Research Articles

PON3::LCN1 and HTN3::MSANTD3 Gene Fusions With NR4A3/NR4A2 Expression in Salivary Acinic Cell Carcinoma.

Acinic cell carcinoma of the salivary gland (AciCC) is a low-grade carcinoma characterized by the overexpression of the transcription factor nuclear receptor subfamily 4 group A member 3 (NR4A3). AciCC has been the subject of a few molecular research projects. This study delves into AciCC's molecular landscape to identify additional alterations and explore their clinical implications. RNA sequencing and immunohistochemical staining for markers NR4A3/NR4A2, DOG-1, S100, and mammaglobin were utilized on 41 AciCCs and 11 secretory carcinoma (SC) samples. NR4A3 was evident in 35 AciCCs, while the residual 6 were NR4A3-negative and NR4A2-positive; SC samples were consistently NR4A3-negative. A novel fusion, PON3 exon 1- LCN1 exon 5, was detected in 9/41 (21.9%) AciCCs, exhibiting a classical histologic pattern with serous cell components growing in solid sheets alongside the intercalated duct-like component. Clinical follow-up of 39 patients over a median of 59 months revealed diverse prognostic outcomes: 34 patients exhibited no disease evidence, whereas the remaining 5 experienced poorer prognosis, involving local recurrence, lymph node, and distant metastasis, and disease-associated death, 4 of which harbored the PON3::LCN1 fusion. In addition, the HTN3::MSANTD3 fusion was recurrently identified in 7/41 AciCC cases. SC patients lacked both fusions. Immunohistochemistry uncovered differential expression of DOG-1, S100, and mammaglobin across samples, providing nuanced insights into their roles in AciCC. This study accentuates PON3::LCN1 and HTN3::MSANTD3 fusions as recurrent molecular events in AciCC, offering potential diagnostic and prognostic utility and propelling further research into targeted therapeutic strategies.

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.

Genetic and Immunohistochemical Profiling of Mammary Hidradenoma and Comparison to Mucoepidermoid Carcinoma

Mucoepidermoid carcinoma (MEC) is exceedingly rare in the breast, with <45 cases reported in the literature. Although estrogen receptor/progesterone receptor/human epidermal growth factor 2 triple-negative, MEC is characterized as a special subtype of breast carcinoma with significantly better prognosis than conventional basal-type tumors. Cutaneous hidradenoma (HA) is considered a benign adnexal neoplasm showing histomorphologic overlap with MEC. Rare cases of HA have also been reported in the breast, but these are relatively uncharacterized. In this study, we examined the clinicopathologic, immunohistochemical (IHC), and genetic features of 8 breast HAs, in comparison to 3 mammary MECs. All cases were positive for MAML2 break-apart fluorescence in situ hybridization. Eight cases demonstrated a CRTC1::MAML2 fusion, and one MEC harbored a CRTC3::MAML2 fusion; the latter is a novel finding in the breast. Mutational burden was very low, with only one HA exhibiting a MAP3K1 pathogenic alteration. By IHC, both MEC and HA demonstrated cell type–dependent expression of high- and low-molecular-weight keratins and p63, as well as negative to low-positive estrogen receptor and androgen receptor. Smooth muscle myosin and calponin highlighted an in situ component in the 3 cases of MEC; expression of these myoepithelial markers was negative in HAs. Additional distinguishing characteristics included the growth pattern and tumor architecture, the presence of glandular/luminal cells in HA, and overall higher IHC expression of SOX10, S100 protein, MUC4, and mammaglobin in MEC. Morphologic findings were also compared to a series of 27 cutaneous nonmammary HAs. Mucinous and glandular/luminal cells were identified in significantly more mammary HAs than nonmammary lesions. The findings provide insight into the pathogenesis of MAML2-rearranged neoplasms of the breast, underscore the overlapping genetic features of MEC and HA, and highlight similarities to their extramammary counterparts.

Survival analysis of breast cancer patients luminal subtype B on lymphovascular invasion (LVI), tumor-infiltrating lymphocyte (TIL), and expression of mammaglobin A

Background: With 1 in 10 women receiving a new cancer diagnosis each year, breast cancer is the most frequent cancer among women. Luminal B breast cancer incidence rates are rising in non-Hispanic white women aged 55 to 69 in Asia/Pacific and Indonesia subtype across all age groups. In Bali, Luminal B is the most prevalent subtype with the greatest fatality rate. This study aims to prove the survival analysis of Luminal B subtype breast cancer patients based on lymphovascular invasion (LVI), tumor-infiltrating lymphocyte (TIL), and mammaglobin A expression. Methods: This study is a survival analysis using nested and prospective cohort methods. Retrospective data were taken from the Cancer Registry and Medical Records (MR) of patients in Sanglah General Hospital, mammaglobin results (Paraffin block test) on anatomical pathology analysis. Statistical Kaplan Meier and Cox Proportional hazard calculations performed with the SPSS program were significant (p&lt;0.05). Results: The number of research subjects was 60, with 32 subjects dying and 28 still alive until the data collection was completed. There was no difference in age between the two groups. The mean of all ages is 50.12 ± 9.93 years. Positive LVI has 9 months median survival (95% CI 8-10) with p= 0.013 risk 2,797 times. TIL high (positive 2- positive 3) median survival 8 months (95% CI 6.3-9.7) with p=0.003 and risk 3,151 times. Strong expression of mammaglobin A (3-4) had a median survival of 12 months (95% CI 4.4-19.5 months; p=0.015) and risk 3.34 times. Conclusion: LVI, TIL, and mammaglobin A expression significantly affected poor survival in the breast cancer Luminal B subtype.

A comprehensive immunohistochemical analysis of 26 markers in 250 cases of serous ovarian tumors

BackgroundWe examined a large cohort of serous tubo-ovarian tumors with 26 immunohistochemical markers, with the aim to assess their value for differential diagnosis and prognosis.MethodsImmunohistochemical analyses with 26 immunomarkers were performed on 250 primary tubo-ovarian tumors including 114 high grade serous carcinomas (HGSC), 97 low grade serous carcinomas (LGSC), and 39 serous borderline tumors (micropapillary variant, mSBT). The associations of overall positivity with clinicopathological characteristics were evaluated using the chi-squared test or Fisher’s Exact test.ResultsWe found significantly different expression of p53, p16, ER, PR, PTEN, PAX2, Mammaglobin, RB1, Cyclin E1, stathmin, LMP2, L1CAM, CD44, and Ki67 in HGSCs compared to LGSCs. No significant differences were found between LGSC and mSBT. None of the other included markers (PAX8, ARID1A, HNF1B, Napsin A, CDX2, SATB2, MUC4, BRG1, AMACR, TTF1, BCOR, NTRK) showed any differences between the investigated serous tumors. Regarding the prognosis, only PR and stathmin showed a statistically significant prognostic meaning in LGSCs, with better overall survival (OS) and recurrence-free survival (RFS) in cases positive for PR, and worse outcome (RFS) for stathmin. None of the study markers showed prognostic significance in HGSCs.ConclusionWe provided an extensive immunohistochemical analysis of serous ovarian/tubo-ovarian tumors. Although we found some differences in the expression of some markers in HGSCs compared to LGSCs, only p53, p16, and Ki67 seem to be useful in real diagnostic practice. We also suggested the best discriminative cut-off for Ki67 (10% of positive tumor cells) for distinguishing HGSC from LGSC. We found prognostic significance of PR and stathmin in LGSCs. Moreover, the high expression of stathmin could also be of predictive value in ovarian carcinomas as target-specific anti-stathmin effectors are potential therapeutic targets.

Characterization of GATA3 and Mammaglobin in breast tumors from African American Women

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.

A clinical diagnostic test on the detection of sentinel lymph node metastasis in breast neoplasms using a 1-step RT-PCR.

Currently, assessment of sentinel lymph node (SLN) requires cytology, hematoxylin-eosin (HE), and immunohistochemistry (IHC). However, routine pathological slides still suffer from certain sampling errors and have time limitations. This study sought to investigate the sensitivity and specificity of SLN detection by reverse transcription-polymerase chain reaction (RT-PCR), which quantifies the expression of mammaglobin and cytokeratin-19 genes to determine SLN status. The RT-PCR detection of cycles threshold (CT) values has a direct relationship with the lymph node metastasis. This study prospectively collected 256 sentinel lymph nodes from 150 patients diagnosed with breast cancer between August and November 2017. In the detection of metastases in lymph nodes, molecular markers can be verified at the cell-level and tissue-level of tumor cells. In this study, IHC results were used as the gold standard for judging sentinel lymph node status. (I) According to the established cell models, as the lymph nodes in tumor cells increase, RT-PCR CT values decrease. (II) 83 lymph nodes were first collected, and the interpretation criteria for the molecular detection results were determined based on the IHC results. (III) The statistical analysis showed that the sensitivity of the RT-PCR was 80.49% and the specificity was 91.55%. The positive predictive and negative predictive values were 64.71% and 96.06%, respectively. There was no significant difference between RT-PCR detection and IHC detection (P=0.076). Statistical chi-square analysis also showed that the difference between intraoperative freezing and immunohistochemistry was statistically significant (P=0.000). There was a statistically significant difference between intraoperative freezing and RT-PCR detection (P=0.000). RT-PCR detection is more sensitive than intraoperative frozen detection, and is closer to the results of immunohistochemistry. RT-PCR had objective and rapid output advantages, and was proven to be true and reliable. RT-PCR detection can not only rapidly assess sentinel lymph node status in breast cancer patients during surgery, but its accuracy is also close to that of IHC. Correctly determine whether to perform axillary lymph node dissection and improve the survival rate of patients.

Secretory Carcinoma of the Salivary Glands

&#x0D; &#x0D; &#x0D; &#x0D; A 29-year-old woman presented with a 3-month history of an enlarging right infra-auricular mass. A fine needle aspiration biopsy revealed a cellular aspirate consistent with a salivary gland neoplasm of uncertain malignant potential (The Milan System for Reporting Salivary Gland Cytopathology Category IV-B). She subsequently underwent superficial parotidectomy, revealing a poorly circumscribed tumor measuring 1.8 x 1.2 x 1.0 cm in the superficial lobe of the parotid gland.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; On microscopic examination, the tumor was composed of microcystic, follicular, and tubular structures lined by mildly atypical, hobnailed cells with abundant granular to foamy, pale, eosinophilic cytoplasm, and round to oval, vesicular nuclei containing finely granular chromatin and prominent, centrally located nucleoli. (Figure 1) Intraluminal secretions were present within the microcysts and tubules, staining positive for Periodic Acid Schiff (PAS) that was resistant to diastase digestion. (Figure 2) Immunohistochemistry studies for S100, SOX10, and Mammaglobin showed strong, diffuse positivity in the tumor cells, in contrast to the absence of staining observed for DOG1. (Figure 3) Given the described morphological and immunological findings, a diagnosis of secretory carcinoma was rendered. No foci of high-grade transformation, i.e., areas with a solid growth pattern, nuclear anaplasia, increased mitoses, or necrosis, were noted.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Secretory Carcinoma or Mammary Analogue Secretory Carcinoma (MASC) is a recently described low grade salivary gland malignancy that bears a morphologic resemblance to mammary secretory carcinoma, harboring a similar chromosomal translocation, t(12;15) (p13;q25), that most commonly produces a fusion of the ETV6 and NTRK3 genes.1-5 Occurring in adults (mean patient age of 46.5 years) without a predilection for either sex, these tumors most commonly arise in the parotid gland.1,2&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Historically, secretory carcinomas have been diagnosed as either acinic cell carcinoma – due to the close morphological similarity of having a microcystic or follicular growth pattern or adenocarcinoma that is not otherwise specified. Aside from the characteristic ETV6-NTRK3 gene fusion, secretory carcinomas may be differentiated from acinic cell carcinoma by having no basophilic zymogen cytoplasmic granules in the tumor cells in contrast to the latter, and the diffuse expression of S100 and Mammaglobin as well as the absence of DOG1 expression in secretory carcinoma on immunohistochemistry. 1,2 Low grade mucoepidermoid carcinoma may also present as a possible morphological differential diagnosis. Immunohistochemistry studies for p63 (expressed in epidermoid cells of mucoepidermoid carcinoma), as well as S100 and Mammaglobin (no expression expected in mucoepidermoid carcinoma) may be sufficient to differentiate between the two entities. On a cytogenetic level, most low grade mucoepidermoid carcinomas harbor a chromosomal translocation, t(11:19), that results in a characteristic CRTC1-MAML2 gene fusion in contrast to the ETV6-NTRK3 fusion seen in secretory carcinoma.1-3 The light microscopic features of this particular case however are sufficiently distinct from a mucoepidermoid carcinoma that we felt that this entity could be excluded based on routine H&amp;E morphology. It is granted however, that molecular testing, e.g., in-situ hybridization to demonstrate characteristic chromosomal aberrations, may prove valuable in morphologically ambiguous cases. Its unavailability in the local setting is thus a limitation.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; Secretory carcinomas are mostly reported to be indolent though are associated with lymph node metastasis in up to 25% of cases. Like other low grade salivary gland carcinomas, locoregional recurrence and distant metastasis have been documented in rare cases. However, high clinical grade and high-grade morphological transformation have been reported and are associated with adverse outcomes.1,2,4,5 The patient tolerated the surgical procedure well, and had no evidence of disease eight months after the operation. Reporting this fairly uncommon entity is encouraged to further expand our understanding of its biology and natural history.&#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D; &#x0D;

Secretory carcinoma of salivary gland: a clinicopathological and prognostic analysis of twelve cases

Objective: To study the clinical manifestations, pathological features, molecular features, differential diagnosis and prognosis of secretory carcinoma of salivary gland (SCSG). Methods: Twelve cases of SCSG diagnosed in the Department of Pathology, the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2019 were collected and analyzed in terms of histological morphology, immunohistochemistry (Envision method) and molecular detection. Results: Among the 12 patients, there were 6 males and 6 females, aged 12-67 years old, with a median age of 41.5 years. The lesions in 11 patients were located in the parotid gland. The maximum diameter of the tumors ranged from 0.8 to 5.5 cm. Clinically, slow-growing painless or tender mass was the first symptom, and all patients underwent surgical resection, among which 5 patients received postoperative radiotherapy and chemotherapy, and 1 patient developed local recurrence. Histopathologically, the tumor is characterized by microcystic, solid or tubular structures with unique intravitary homogeneous secretions. Immunohistochemistry showed diffuse expression of CK7, mammaglobin, GATA-3 and S-100 in all cases, and pan-Trk in 10 of the 12 cases. Sox-10 was expressed focally in 9 cases, and Ki-67 index was 5%-20%. In molecular detection, 11 cases had ETV6 gene break/fusion. Conclusions: SCSG is a relatively rare low-grade malignant salivary gland tumor, with typical histological morphology and immunophenotype, Pan-Trk immunohistochemistry may be related to NTRK fusion, ETV6-NTRK3 gene rearrangement is not only of diagnostic significance, but also Trk-targeted therapy is expected to play a greater role in clinical treatment.

Mammaglobin expression in tissue as a predictor of breast carcinoma aggressiveness

Background/Aim. Human mammaglobin is considered to be one of the most significant markers of hematogenous dissemination of breast carcinoma. This paper aimed to indicate the important role of peritumoral tissue as an active participant in the tumorigenesis process and the concentration/expression of mammaglobins in the peritumoral tissue as a significant prognostic factor. Methods. This research included 64 female patients with primary breast carcinoma during the five-year follow-up period. To determine the concentration of mammaglobin A in samples of carcinoma tissue and peritumoral tissue, Enzyme-linked immunosorbent assay (ELISA) test was used, and for the determination of relative gene expression of mammaglobin A, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used. Results. The concentration of mammaglobin A was increased in both the carcinoma tissue and peritumoral tissue with an increase in tumor size, number of affected lymph nodes, number of metastases, while relative expression of mammaglobin A was statistically significantly higher in carcinoma tissue than in peritumoral tissue, regardless of the tumor size, number of affected lymph nodes, number of metastases and tumor type. The concentration of mammaglobin A was higher in peritumoral tissue than in tissue of ductal carcinoma, while in the case of lobular carcinoma the concentration of mammaglobin A was higher in carcinoma tis-sue than in peritumoral tissue. Conclusion. Mammaglobin A concentration in peritumoral tissue higher than 0.6704221 ng/mL, and in carcinoma tissue higher than 0.5784426 ng/mL, as well as mammaglobin A relative gene expression in carcinoma tissue higher than 1.003, were determined as cut-off values. These values may identify patients who are at higher risk of metastatic disease, which would be treated with early radical adjuvant treatment.

Mammaglobin protein localization and gene expression in the salivary glands.

This study aims to delve deeper into the hypothesis that normal salivary gland tissue expresses both protein and mRNA of mammaglobin (MGB). Formalin-fixed paraffin-embedded samples of submandibular (10), parotid (5), palatal (5) and labial glands (30) salivary glands were immunohistochemically investigated. The labial samples were used to examine the MGB positive ratio (MGB-PR), and localize MGB by double immunofluorescence staining and quantitative mRNA gene expression. Mann-Whitney U and Kruskal Wallis rank-sum test for group comparison, and Spearman's rank correlation coefficient for correlation analysis were used. The distribution of MGB-positive cells was variable throughout samples with significantly higher MGB-PR of acini than ducts (P = 0.00376), and there was no difference when compared based on age (P = 0.0646) and gender (P = 0.245). Besides acinar cells, a number of myoepithelial cells and ductal cells also demonstrated strong MGB reactivity with varying MGB mRNA expression levels in 6 of the 7 samples (with MGB-PR > 20%) tested. This novel study shows that unlike aberrant protein expression in some carcinomas, MGB expression in salivary gland neoplasms represents the nature of original cells, giving a better insight into the neoplasms expressing MGB.

MUC4 is a valuable marker for distinguishing secretory carcinoma of the salivary glands from its mimics.

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. 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). 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.

IMMUNOHISTOCHEMICAL EXPRESSION OF METABOLIC MARKERS IN PLEOMORPHIC ADENOMA AND CARCINOMA EX PLEOMORPHIC ADENOMA

Objective: To perform a comparative study focusing on the morphologic and immunohistochemical features of pleomorphic adenomas (PAs) and carcinoma ex pleomorphic adenomas (CXPAs) of the minor salivary glands. Study design: Forty PAs and 10 CXPAs were retrieved from the archives of 3 pathology laboratories, and the diagnoses were reviewed and confirmed. Immunohistochemical reactions were done for p53, Ki67, mammaglobin, and the metabolic markers of glucose transporter 1 (GLUT-1) and adipophilin. Results: The most common subtypes of CXPA were ductal carcinoma (n = 4), clear cell carcinoma (n = 3), and myoepithelial carcinoma (n = 2). The morphologic features suggestive of malignancy were the presence of mitosis, cellular pleomorphism, and extracapsular component. Compared to PA, CXPA demonstrated a higher number of Ki67- and p53-positive cells, in addition to higher expression of GLUT-1 and adipophilin. Mammaglobin expression was observed in the malignant areas, mainly in the ductal CXPA, being negative in the benign reminiscent PA. Conclusion: The diagnosis of CXPA based only on the morphologic aspects can be difficult; thus, an association of the morphologic and immunohistochemical features, particularly high number of Ki67- and p53-positive cells, is essential for a proper diagnosis. Other metabolic markers such as GLUT-1 and adipophilin may be also helpful, although their exact utility remains to be determined.

Breast mucinous cystadenocarcinoma – case report

Introduction: Mucinous cystadenocarcinoma (MCC) is a rare primary breast tumor, first described in 1998. It was removed from the WHO classification in 2012, due to lack of consensus about its definition. To our knowledge, only 25 cases have been published in the literature. Objective: Case report and discussion of a case of breast MCC diagnosed in Centro de Doenças da Mama in Curitiba. Case report: Premenopausal 51 year-old patient, complaining of pain and nodule in the left breast. Physical examination showed a palpable nodule of approximately 2 cm, in the UOQ of the left breast. The ultrasound showed a 2.3 cm nodule, BI-RADS 5, submitted to core-needle biopsy with diagnosis of carcinoma with mucinous differentiation, positive for estrogen receptor (ER). The PET-Scan did not show extramammary site capture. Conserving surgery and sentinel lymph node were performed, with breast reconstruction using the geometric compensation technique. Macroscopy showed a cystic and solid mass, of mucinous content, measuring 4.0x3.5 cm. The histological status was suggestive of MCC, with 2 negative sentinel lymph nodes. The IQ showed mammaglobin expression, CK7 and ER, negative expression of c-erbB-2, CK20 and CK5/6. The patient was submitted to radiotherapy and hormone therapy. Discussion: The primary breast MCC needs to be distinguished from ovarian and pancreatic metastasis. The IQ for CK7 and CK20 can be useful, considering that the pancreatic and ovarian MCC have concomitant expression of CK7 and CK20; the breast MCC expresses only CK7. In the 26 cases described in the literature, including this study, mean age was 62 years (41‒96), and the tumor size was variable (0.8–19 cm). Only 4 cases presented positive lymph nodes. Most described cases did not express ER. The reported cases were associated with good prognosis. Conclusion: A consensus on the histological nomenclature and longer follow-up time are necessary to better understand this variant.

CARCINOMA EXPLEOMORPHIC ADENOMA WITH FOCAL ABERRANT MAMMAGLOBIN EXPRESSION

A 70-year-old male patient sought dental care for oral rehabilitation. A painless firm nodule covered by normal mucosa was detected during the examination in the retromolar region. The lesion was well circumscribed, and an excisional biopsy was performed. Histopathologic analysis revealed a partially encapsulated tumor composed by sheets and islands of ductal-type epithelial cells with moderate cytologic atypia. Pseudocystic ductal spaces and areas of a trabecular patterns with extensive stromal hyalinization were observed. Immunohistochemical results from CK7, CK14, S100, smooth muscle actin, calponin, p63, and Ki67 were consistent with carcinoma ex pleomorphic adenoma (CaExPA). Interestingly, the tumor demonstrated a focal yet strong positivity for mammaglobin. The ETV6-NRKT3 translocation, however, was absent. Therefore, a final diagnosis of CaExPA with focal aberrant mammaglobin expression was established. The patient was referred to a head and neck surgeon and submitted to a new surgical procedure. No recurrence was detected after 6 months. A 70-year-old male patient sought dental care for oral rehabilitation. A painless firm nodule covered by normal mucosa was detected during the examination in the retromolar region. The lesion was well circumscribed, and an excisional biopsy was performed. Histopathologic analysis revealed a partially encapsulated tumor composed by sheets and islands of ductal-type epithelial cells with moderate cytologic atypia. Pseudocystic ductal spaces and areas of a trabecular patterns with extensive stromal hyalinization were observed. Immunohistochemical results from CK7, CK14, S100, smooth muscle actin, calponin, p63, and Ki67 were consistent with carcinoma ex pleomorphic adenoma (CaExPA). Interestingly, the tumor demonstrated a focal yet strong positivity for mammaglobin. The ETV6-NRKT3 translocation, however, was absent. Therefore, a final diagnosis of CaExPA with focal aberrant mammaglobin expression was established. The patient was referred to a head and neck surgeon and submitted to a new surgical procedure. No recurrence was detected after 6 months.

Microvessel Density and Mammaglobin A Expression as Prognostic Markers in Molecular Types of Breast Cancer

Increased microvessel density (MVD) values in breast cancer correlate with tumor growth and progression while mammaglobin (MGB) expression in tumor cells is associated with a favorable prognosis. We aim to evaluate and correlate MVD values with MGB expression in molecular types of breast cancer specimens and to determine their utility as prognostic biological markers. A number of 52 breast cancer specimens were included in the study. Specimens were processed for routine histopathological diagnosis followed by the molecular classification by means of estrogen (ER), progesterone (PR) and HER2 immunohistochemical reactions. After performing immunohistochemistry for CD34 and MGB, MVD evaluation was made using the �hot spot� method for each case and MGB was scored between 0 (negative) and +3 (strong positive) depending on the intensity and distribution of the staining. MGB expression in tumor cells and MVD mean values were extremely variable. The greatest MVD mean values were obtained in luminal B followed by HER2, luminal A and triple negative breast cancer (TNBC) (95.33, 69, 62, and 40, respectively). MGB expression in the tumor cells generally ranged from mild to weak and was strong only in a few invasive ductal carcinoma cases. In cases with TNBCs the expression of MGB in tumor cells was weak and focal or negative. This variability was noticed between the molecular types of breast cancers and even within the same molecular type. In a restricted number of cases, MGB positive tumors were associated with low MVD values while the negative cases were characterized by increased MVD mean values. The variable results we obtained regarding the correlation between MVD and MGB in breast cancer specimens may indicate a rather restricted use of MVD/MGB in estimating breast cancer patients� prognosis.

Immunohistochemical expression of mammaglobin in salivary duct carcinomas de novo and salivary duct carcinoma ex pleomorphic adenoma

Mammaglobin is expressed in breast and salivary gland secretory carcinomas; however, its expression in salivary duct carcinomas (SDCs) still not well established. Therefore, the aim of this study was to investigate the presence and distribution of mammaglobin immunoexpression in SDC ex-PA in different phases of the adenoma to carcinoma sequence evaluating its possible involvement in carcinogenesis and tumor progression, as well as to determine its expression in SDC de novo. Mammaglobin immunohistochemistry was performed in 84 SG tumors, including 41 pleomorphic adenomas (PA) without malignant transformation, 13 intracapsular SDC ex-PA, 5 frankly invasive SDC ex-PA, 25 SDC de novo and 10 secretory carcinomas. The reactions were qualitatively analyzed and digitally scored. Positive immunostaining for mammaglobin was observed in 37 out of 84 SG tumors evaluated (44.1%), but strong staining was consistently seen only in secretory carcinomas, SDC de novo and frankly invasive SDC ex-PA, while it was weaker in intracapsular SDC ex-PA and PA. In PA, mammaglobin expression was significantly associated with recurrence. This study has confirmed that the mammaglobin is commonly expressed in SDC de novo and secretory carcinomas. Its expression was higher in SDC ex-PA than in PA, suggesting that mammaglobin may play a role in its malignant transformation.

Abstract P2-08-61: FOXA1, Nestin, GATA3 and mammaglobin expression in 164 breast cancer metastases – A retrospective immuno-histochemical study of a 10-year period (2004-2014)

Abstract Background. Including additional genes in standard immunohistochemical panels might be helpful in determining the prognosis of breast cancer patients. Pevious studies have shown that FOXA1 is a significant predictor of good outcome in breast cancer, while Nestin expression was preferentially found in triple-negative breast cancers, revealing a strong association with germline BRCA1-related breast cancer, a basal-like phenotype, stemness characteristics, high proliferation rates, p53 nuclear expression, increased rate of nodal metastases, and reduced survival (1,2,3,4). ATA3 was not only an important luminal marker, but a reliable immunohistochemical marker, which plays a crucial diagnostic role in verification of breast cancer metastases (Figure 1. and Figure 2). In a cohort containing 164 breast cancer metastases, we found GATA3 to be a reliable and sensitive diagnostic marker. We verified that the metastases originate from breast carcinoma with 95% GATA3-positivity, while mammaglobin showed only 51.2% positivity (5). According to the mammaglobin immunohistochemical prolife, we evaluated the expression of FOXA1, Nestin and GATA3 in mammaglobin-positive (n=84) and mammaglobin-negative (n=80) samples. aterials and method Full-face formalin-fixed paraffin-embedded (FFPE) specimens for 164 breast cancer metastases (from various anatomical sites) diagnosed between 2004 and 2014 were obtained from the Department of Clinical Pathology and Genetics at Sahlgrenska University Hospital (Gothenburg, Sweden). Each FFPE specimen was examined for mammaglobin, ER/PR, CK7, CK20, and HercepTest at the time of diagnosis and retrospectively analyzed for FOXA1, Nestin and GATA3 expression by immunohistochemistry (IHC). The statistical analyses were performed using a .05 P-value cutoff in R/Bioconductor (version 2.15.0) and all P-values are two-sided. The relationship between clinicopathological features and mammaglobin/GATA3 protein expression patterns was evaluated using two-tailed Fisher's exact test. Results In mammaglobin-positive metastases, FOXA1-positivity was associated with ER+ (83%) and negatively associated with triple-negativity (81%; Figure 3.). Moreover, there was no association between Nestin-positivity and the established clinicopathological features in mammaglobin-positive samples (Table 1 and Figure 4). In mammaglobin-negative samples, FOXA1-positivity was associated with GATA3+ (100%), ER+ (77%), HER2+ (36%), and triple-negative status (82% were non-triple negative). In addition, Nestin-positivity was associated with specific metastatic sites (mostly brain, but even gynecological sites and skin), GATA3- (29%), ER- (50%), PR- (79%), and triple-negative status (50% were triple negative) in mammaglobin-negative samples (Table 2). Conclusion In the present study, we found that FOXA1 was expressed mostly in ER-positive breast cancer metastases and Nestin expression was associated with breast cancer metastases with a triple-negative immune profile, where the brain was the most frequent metastatic site. Citation Format: Nyqvist J, de Lara S, Parris TZ, Helou K, Kenne Sarenmalm E, Einbeigi Z, Karlsson P, Kovács A. FOXA1, Nestin, GATA3 and mammaglobin expression in 164 breast cancer metastases – A retrospective immuno-histochemical study of a 10-year period (2004-2014) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-61.

The role of circulating tumor cells in metastatic breast cancer: prognostic and predictive value.

The aim of the current study was to assess the prognostic value of circulating tumor cells (CTCs) and their related markers at different points of chemotherapy regimens in metastatic breast cancer (MBC) patients. The impact of CTCs on progression free survival (PFS) and overall survival (OS) rates were also assessed. Peripheral blood samples were obtained from 66 female patients with MBC at different time intervals for evaluation of CTCs by flow cytometry (FC). cytokeratin 19 (CK19), mammaglobin, prolactin inducible peptide (PIP), aldehyde dehydrogenase 1 (ALDH1) and human chorionic gonadotropin (hCG) were also assessed by qRT-PCR. Analysis of different CTC levels (at 4, 5, and 6 cells/7ml), showed statistically significant values at 4 cells/7ml blood. The presence of baseline CTCs < 4 cells/7ml, associated significantly with higher PFS (P value = 0.03). Patients showing a decrease in the CTCs level after treatment had significantly prolonged median PFS and OS rates compared to those whose CTCs level increased (P = 0.007 and P = 0.014; respectively). Mammaglobin, CK19, PIP, ALDH1 and hCG expression did not affect PFS or OS. However, patients with CTCs ≥ 4at diagnosis had higher rates of progression compared to those with CTCs < 4 (1.9 times, P = 0.07), and who metastasized before 4years showed a worse decrease outcomes (they were 2.4 time more progressed than those who metastasized after 4 years; P = 0.029). CTCs could be an independent prognostic and predictive biomarker for MBC patients' outcomes. Although none of the assessed genes (mammaglobin, CK19, PIP, ALDH1 and hCG) showed correlation with PFS or OS rates, further studies on a larger number of patients are required to validate the current results.

393 (PB-026) - FOXA1, Nestin, GATA3 and Mammaglobin expression in 164 breast cancer metastases – a retrospective immunohistochemical study of a 10-year period (2004–2014)

393 (PB-026) - FOXA1, Nestin, GATA3 and Mammaglobin expression in 164 breast cancer metastases – a retrospective immunohistochemical study of a 10-year period (2004–2014)