Cystic Disease Fluid Protein Research Articles

Single-cell multiplex immunocytochemistry in cell block preparations of metastatic breast cancer confirms sensitivity of GATA-binding protein 3 over gross cystic disease fluid protein 15 and mammaglobin.

Metastatic breast cancers are frequently encountered in cytology and require immunocytochemistry (ICC). In this study, traditional and multiplex ICC (mICC) for GATA-binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP15), and mammaglobin (MMG) were performed with the aim of validating mICC in cell blocks, with further single-cell expression pattern analysis to identify the single markers and combinations of markers most sensitive in subtypes of breast cancer. GATA3, GCDFP15, and MMG were paired with OptiView 3,3'-diaminobenzidine and Ventana DISCOVERY Purple and Blue, respectively, with cyclical and serial staining. Bright-field imaging was performed with the Mantra 2 system and analyzed with the inForm Tissue Finder (Akoya Biosciences). Cell detection and phenotyping were further confirmed by two pathologists. In the 36 cases studied, traditional ICC and mICC demonstrated good concordance (kappa coefficient, >0.5; p<.01) at three cutoffs (1%, 5%, and 50%), except for GATA3 at the 1% cutoff. Single-marker positivity outnumbered double-marker positivity and the exceedingly rare triple-marker positivity (<3%). GATA3 was the leading single marker-positive phenotype in all breast cancer subtypes, except for MMG in estrogen receptor-positive, progesterone receptor-positive, and human epidermal growth factor receptor 2-positive (ER+/PR+/HER2+) breast cancers. Limited to two markers, GATA3/MMG included the greatest number of tumor cells for luminal breast cancers (ER+/PR+/HER2+, 60.6%; ER+/PR+/HER2+, 31.4%), whereas HER2-overexpressed breast cancers (27.4%) and triple-negative breast cancers (26.4%) favored the combination of GATA3/GCDFP15. For a single marker, GATA3 displayed the highest sensitivity. The addition of MMG for hormone receptor-positive breast cancers and GCDFP15 for hormone receptor-negative breast cancers further increased sensitivity. The low proportion of multimarker-positive cells suggested that the coexpression observed with traditional ICC is attributable to intratumoral heterogeneity, not genuine coexpression.

TRPS1, a sensitive marker for different histological and molecular types of breast cancer

ObjectivesWe explored Trichorhinophalangeal syndrome type 1 (TRPS1) expression in special types of breast carcinoma, and analyzed the correlation between TRPS1 and androgen receptor (AR) expression in triple-negative breast cancer (TNBC).MethodsTRPS1 expression was analyzed in 801 patients with special types of breast carcinoma. A total of 969 TNBC were used to analyze the correlation between the expression of TRPS1 and AR. TRPS1 expression was evaluated in 1975 cases of breast cancer with different molecular types.ResultsA total of 801 special types of breast cancers were stained with TRPS1.TRPS1 was positive in 100% (63/63) of mucinous carcinoma, 100% (7/7) adenoid cystic carcinomas (4 classic adenoid cystic carcinomas and 3 solid-basaloid adenoid cystic carcinomas), 100% (4/4) tubular carcinomas, 100% (2/2) secretory carcinomas, and 99.59% (243/244) invasive lobular carcinomas, 99.26% (267/269) invasive micropapillary carcinomas, 97.44% (38/39) ER-positive neuroendocrine tumors, 94.44% (34/36) metaplastic breast carcinomas (MBCs), 63.73% (65/102) apocrine carcinomas. TRPS1 was negative in all triple-negative neuroendocrine carcinomas (0/7).TRPS1 was positive in 92.86% (26/28) of metastatic special types of breast cancer. TRPS1 and AR expression were analyzed in 969 cases of TNBC. 90.40% were positive for TRPS1, and 42.41% were positive for AR. A significant inverse correlation between TRPS1 and AR expression was shown in TNBC (p < .001). TRPS1 showed a higher positive rate (93.13%) in TNBC compared to GATA binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP-15) and forkhead box transcription Factor C 1 (FOXC1).ConclusionsIn conclusion, our study demonstrated that TRPS1 is a highly sensitive marker for most special types of breast carcinoma. TRPS1 was positive in 63.73% of apocrine carcinomas. TRPS1 and AR expression was inversely correlated in TNBC.

Deciphering Breast Origin in Malignant Effusions: The Diagnostic Utility of an MGP, GATA-3, and TRPS-1 Immunocytochemical Panel

Introduction: Defining the origin of metastatic cancer is crucial for establishing an optimal treatment strategy, especially when obtaining sufficient tissue from secondary malignancies is limited. While cytological examination is often used in this diagnostic setting, morphologic analysis alone often fails to differentiate metastases derived from the breast from other primaries. The hormone receptor, human epidermal growth factor receptor-2, gross cystic disease fluid protein 15, and mammaglobin immunohistochemistry are often used to diagnose metastatic breast cancer. However, their effectiveness decreases in estrogen receptor (ER)-negative breast cancers, including the triple-negative breast cancer (TNBC) subtype. Methods: We conducted a comprehensive evaluation of GATA-binding protein 3 (GATA-3), trichorhinophalangeal syndrome type 1 (TRPS-1), and Matrix Gla Protein (MGP) immunochemistry across 140 effusion cytology specimens with metastatic adenocarcinoma derived from various primaries, including the breast, colon, pancreaticobiliary, lung, tubo-ovarian, and stomach. Results: The expression rates of these immunomarkers were significantly higher in metastatic cancers originating from the breast than other primaries. In TNBC, TRPS-1 (80.00%) and MGP (65.00%) exhibited higher positivity rates compared to GATA-3 (40.00%). Additionally, our data suggest that an immunohistochemical panel comprising MGP, GATA-3, and TRPS-1 significantly enhances the detection of metastatic breast cancer in effusion cytology specimens, including TNBC in particular. When considering dual-marker positivity, the diagnostic accuracy was found to be 89.29% across all breast cancer subtypes and 92.93% for TNBC. Conclusions: MGP appears to be a robust marker for identifying metastatic breast cancer in malignant effusions, especially TNBC. MGP notably enhances diagnostic accuracy when incorporated together with GATA-3 and TRPS-1 in an immunohistochemical panel.

Prognostic Role of Prolactin-Induced Protein (PIP) in Breast Cancer.

Prolactin-inducible protein (PIP), also referred to as gross cystic disease fluid protein 15 (GCDFP-15), has been a trending topic in recent years due to its potential role as a specific marker in breast cancer. PIP binds to aquaporin-5 (AQP5), CD4, actin, fibrinogen, β-tubulin, serum albumin, hydroxyapatite, zinc α2-glycoprotein, and the Fc fragment of IgGs, and the expression of PIP has been demonstrated to be modulated by various cytokines, including IL4/13, IL1, and IL6. PIP gene expression has been extensively studied due to its captivating nature. It is influenced by various factors, with androgens, progesterone, glucocorticosteroids, prolactin, and growth hormone enhancing its expression while estrogens suppress it. The regulatory mechanisms involve important proteins such as STAT5A, STAT5B, Runx2, and androgen receptor, which collaborate to enhance PIP gene transcription and protein production. The expression level of PIP in breast cancer is dependent on the tumor stage and subtype. Higher expression is observed in early-stage tumors of the luminal A subtype, while lower expression is associated with luminal B, basal-like, and triple-negative subtypes, which have a poorer prognosis. PIP expression is also correlated with apocrine differentiation, hormone receptor positivity, and longer metastasis-free survival. PIP plays a role in supporting the immune system's antitumor response during the early stages of breast cancer development. However, as cancer progresses, the protective role of PIP may become less effective or diminished. In this work, we summarized the clinical significance of the PIP molecule in breast cancer and its potential role as a new candidate for cell-based therapies.

Triple-negative Breast Carcinoma With Apocrine and Histiocytoid features: A Clinicopathologic and Molecular Study of 18 Cases.

Triple-negative breast cancer (TNBC) is a heterogenous group of tumors. Most TNBCs are high-grade aggressive tumors, but a minority of TNBCs are not high grade, with relatively indolent behavior and specific morphologic and molecular features. We performed a clinicopathologic and molecular assessment of 18 non-high-grade TNBCs with apocrine and/or histiocytoid features. All were grade I or II with low Ki-67 (≤20%). Thirteen (72%) showed apocrine features, and 5 (28%) showed histiocytoid and lobular features. In all, 17/18 expressed the androgen receptor, and 13/13 expressed gross cystic disease fluid protein 15. Four (22.2%) patients were treated with neoadjuvant chemotherapy, but none achieved a pathologic complete response. In all, 2/18 patients (11%) had lymph node metastasis at the time of surgery. None of the cases had a recurrence or disease-specific death, with an average follow-up time of 38 months. Thirteen cases were profiled by targeted capture-based next-generation DNA sequencing. Genomic alterations (GAs) were most significant for PI3K-PKB/Akt pathway (69%) genes, including PIK3R1 (23%), PIK3CA (38%), and PTEN (23%), and RTK-RAS pathway (62%) including FGFR4 (46%) and ERBB2 (15%). TP53 GA was seen in only 31% of patients. Our findings support those on high-grade TNBCs with apocrine and/or histiocytoid features as a clinicopathologic and genetically distinct subgroup of TNBC. They can be defined by features including tubule formation, rare mitosis, low Ki-67 (≤20%), triple-negative status, expression of androgen receptor and/or gross cystic disease fluid protein 15, and GA in the PI3K-PKB/Akt and/or RTK-RAS pathway. These tumors are not sensitive to chemotherapy but have favorable clinical behavior. Tumor subtype definitions are the first step to implementing future trial designs to select these patients.

Frequent apocrine changes in pleomorphic adenoma with malignant transformation: a possible pre-malignant step in ductal carcinoma ex pleomorphic adenoma.

The most common type of carcinoma ex pleomorphic adenoma (CPA) is histologically equivalent to salivary duct carcinoma, which has an apocrine phenotype. Invasive CPA is often accompanied by non-invasive or in situ carcinoma, an observation that suggests the presence of precursor lesions. The aim of this study was to identify candidate precursor lesions of CPA within pleomorphic adenoma (PA). Eleven resected cases of CPA with residual PA and 17 cases of PA with atypical changes were subjected to immunohistochemistry (IHC) for p53, human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), pleomorphic adenoma gene 1, gross cystic disease fluid protein-15 (GCDFP-15), and anti-mitochondrial antibody. Invasive or in situ carcinoma cells in all CPAs were positive for AR, GCDFP-15, and HER2. Atypical foci in PAs corresponded to either apocrine or oncocytic changes on the basis of their reactivity to AR, GCDFP-15, and anti-mitochondrial antibody. Atypical cells in PAs surrounding CPAs had an apocrine phenotype without HER2 expression. Our study identified frequent apocrine changes in residual PAs in CPA cases, suggesting a possible precursor role of apocrine changes. We recommend the use of HER2 IHC in atypical PAs, and that clinicians take HER2 positivity into serious consideration.

TRPS1 expression in cytokeratin 5 expressing triple negative breast cancers, its value as a marker of breast origin

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.

Clinicopathological Features and Prognosis of Gastrointestinal Metastases From Breast Carcinoma: A Clinicopathological Study of 22 Patients.

Background. Breast carcinoma is the most common malignancy in women. Gastrointestinal metastasis is rarely found or diagnosed in patients with breast cancer. Methods. Clinicopathological features, treatment options, and prognosis were evaluated retrospectively for 22 patients with gastrointestinal metastases of breast carcinoma in Chinese women. Results. Presenting symptoms were non-specific: anorexia (21/22), epigastric pain (10/22), and vomiting (8/22), and 2 patients (2/22) presented with nonfatal hemorrhage. The first sites of metastases were skeleton (9/22), stomach (7/22), colorectal (7/22), lung (3/22), peritoneal (3/22), and liver (1/22). ER, PR, GATA binding protein 3 (GATA3), gross cystic disease fluid protein-15 (GCDFP-15), and keratin 7 can effectively confirm the diagnosis, especially in the case of keratin 20 negativity. Histology showed mainly ductal breast carcinoma (n = 11) was the predominant source of gastrointestinal metastases in this study, and lobular breast cancer (n = 9) accounted for a considerable proportion. The disease control rate to systemic therapy was 81% (17 of 21 treated patients), and the objective response rate was 10% (2 of 21 treated patients). Median overall survival was 71.5 months (range, 22-226 months), median survival for distant metastases was 23.5 months (range, 2-119 months) and the median survival for the time of gastrointestinal metastases diagnosis was 6 months (range, 2-73 months). Conclusions. Performing the endoscopy with biopsy was crucial for patients with any subtle gastrointestinal symptoms and a history of breast cancer. It is important to distinguish primary gastrointestinal carcinoma from breast metastatic carcinoma in order to select the optimal initial treatment and avoid unnecessary surgery.

Triple-Negative Apocrine Carcinomas: Toward a Unified Group With Shared Molecular Features and Clinical Behavior

Triple-negative apocrine carcinomas (TNACs) are rare breast tumors with limited studies evaluating their molecular characteristics and clinical behavior. We performed a histologic, immunohistochemical, genetic, and clinicopathologic assessment of 42 invasive TNACs (1 with a focal spindle cell component) from 41 patients, 2 pure apocrine ductal carcinomas in situ (A-DCIS), and 1 A-DCIS associated with spindle cell metaplastic carcinoma (SCMBC). All TNACs had characteristic apocrine morphology and expressed androgen receptor (42/42), gross cystic disease fluid protein 15 (24/24), and CK5/6 (16/16). GATA3 was positive in most cases (16/18, 89%), and SOX10 was negative (0/22). TRPS1 was weakly expressed in a minority of tumors (3/14, 21%). Most TNACs had low Ki67 proliferation (≤10% in 67%, 26/39), with a median index of 10%. Levels of tumor infiltrating lymphocytes were low (≤10% in 93%, 39/42, and 15% in 7%, 3/42). Eighteen percent of TNACs presented with axillary nodal metastasis (7/38). No patients treated with neoadjuvant chemotherapy achieved pathologic complete response (0%, 0/10). Nearly all patients with TNAC (97%, n = 32) were without evidence of disease at the time of study (mean follow-up of 62 months). Seventeen invasive TNACs and 10 A-DCIS (7 with paired invasive TNAC) were profiled by targeted capture-based next-generation DNA sequencing. Pathogenic mutations in phosphatidylinositol 3-kinase pathway genes PIK3CA (53%) and/or PIK3R1 (53%) were identified in all TNACs (100%), including 4 (24%) with comutated PTEN. Ras-MAPK pathway genes, including NF1 (24%), and TP53 were mutated in 6 tumors each (35%). All A-DCIS shared mutations, such as phosphatidylinositol 3-kinase aberrations and copy number alterations with paired invasive TNACs or SCMBC, and a subset of invasive carcinomas showed additional mutations in tumor suppressors (NF1, TP53, ARID2, and CDKN2A). Divergent genetic profiles between A-DCIS and invasive carcinoma were identified in 1 case. In summary, our findings support TNAC as a morphologically, immunohistochemically, and genetically homogeneous subgroup of triple-negative breast carcinomas and suggest overall favorable clinical behavior.

Primary salivary duct carcinoma of the lung: clinicopathological features, diagnosis and practical challenges

AimsTo investigate the clinicopathological features, molecular characteristics and diagnostic criteria of primary salivary duct carcinoma of the lung (LSDC).MethodsWe analysed the clinicopathological and molecular features of five cases of LSDC...

Differential antigen expression between human apocrine sweat glands and eccrine sweat glands

Bromhidrosis has a great negative impact on personal occupation and social psychology. It is not yet clear whether bromhidrosis is caused by apocrine sweat glands or the co-action of apocrine sweat glands and eccrine sweat glands. To distinguish between apocrine sweat glands and eccrine sweat glands, specific antigen markers for apocrine sweat glands and eccrine sweat glands must be found first. In the study, we detected the expression of K7, K18, K19, Na+-K+-2Cl- cotransporter 1 (NKCC1), carbonic anhydrase II (CAII), Forkhead transcription factor a1 (Foxa1), homeobox transcription factor engrailed homeobox1 (En1), gross cystic disease fluid protein-15 (GCDFP-15), mucin-1 (MUC-1), cluster of differentiation 15 (CD15) and apolipoprotein (APOD) in eccrine sweat glands and apocrine sweat glands by immunofluorescence staining. The results showed that K7, K18, K19, Foxa1, GCDFP-15 and MUC-1 were expressed in both apocrine and eccrine sweat glands, CD15 and APOD were only expressed in apocrine sweat glands, and CAII, NKCC1 and En1 were only expressed in eccrine sweat glands. We conclude that CD15 and APOD can serve as specific markers for apocrine sweat glands, while CAII, NKCC1 and En1 can serve as specific markers for eccrine sweat glands to differentiate the two sweat glands.

Gross Cystic Disease Fluid Protein-15 (GCDFP-15) Expression Characterizes Breast Mucinous Carcinomas in Older Women.

The predominant histological subtype of breast mucinous carcinoma in older women is type B (hypercellular type), and, in younger women, it is type A (hypocellular type). The characteristics of mucinous carcinomas of the same histological subtype may differ between older and younger women. This study aims to systematically clarify the pathological/immunohistochemical features of mucinous carcinomas. A total of 21 surgical cases of mucinous carcinoma (type A/B: 9/12 cases) in the older group (≥65 years) and 16 cases (type A/B: 14/2 cases) in the younger group (≤55 years) (n = 37) were included. Gross cystic disease fluid protein-15 (GCDFP-15) and eight other markers were used for immunostaining. The GCDFP-15-positive rate in the older group was high regardless of the histological subtype (type A, 77.8%; type B, 91.7%). The GCDFP-15 positivity in the older group was significantly higher than that in the younger group (p &lt; 0.001 for Allred score). Among type A, GCDFP-15 positivity was significantly higher in the older group than in the younger group (p = 0.042 for the Allred score and p = 0.007 for the positivity rate). The present results suggest that GCDFP-15 expression characterizes mucinous carcinomas in older women.

Her2 expression can predict the survival of patients with salivary duct carcinoma

Salivary duct carcinoma (SDC) is a high-grade malignant tumor that mainly develops in the salivary glands, and SDC patients have a 5-year survival rate of less than 50%. Thirteen SDC patients (11 male and 2 female, average age 67.2 years) with primary salivary gland carcinoma who received primary treatment in our department from 2005 to 2016. Although markers such as androgen receptors and gross cystic disease fluid protein-15 are effective in diagnosing SDC, there are no effective tumor-specific markers for prognosis prediction. Therefore, we investigated the expressions of human epidermal growth factor receptor 2 (Her2), Ki-67, EGFR, p16, P53 and PD-L1, and examined their prognostic effect. Multivariate analysis showed that high Her2 expression was an exacerbating prognostic factor. In the future, the use of molecular-targeted drugs and immune checkpoint inhibitors for salivary gland malignancies may become more frequent. Her2 expression could be used as a predictor of prognosis.

Comparison of GATA3, GCDFP15, Mammaglobin and SOX10 Immunocytochemistry in Aspirates of Metastatic Breast Cancer

Introduction: Metastatic cancers are frequently detected on fine-needle aspiration (FNA) cytology, and confirmation of metastatic breast cancer often requires immunocytochemistry. Tissue provisioning for FNA specimens is important. In this study, GATA3, gross cystic disease fluid protein-15 (GCDFP15), mammaglobin (MMG), and SOX10 were performed on cell block preparations from aspirates of histologically confirmed metastatic breast cancers. The diagnostic performance of single markers and combinations of these markers were investigated with the aim to construct a tissue-efficient immunopanel. Methodology: Aspirates of metastatic breast cancer with corresponding histology and biomarker (estrogen receptor (ER), progesterone receptor (PR), HER2 and ki67) profile were retrieved. ER, GATA3, GCDFP15, MMG and SOX10 immunostains were performed on cell block sections and their expressions were assessed and compared. Results: Immunostaining was performed on a total of 115 aspirates. GATA3 showed the highest expression, followed by MMG, GCDFP15 and SOX10. Twenty-three, five and five cases expressed GATA3, MMG and SOX10 only. The five cases expressing SOX10 only were ER negative, and SOX10 expression was negatively associated with ER (p = 0.001), MMG (p = 0.001), GCDFP15 (p = 0.010) and GATA3 (p = 0.002), whereas GATA3 expression showed positive correlation with ER positivity (p &lt; 0.001). MMG and GCDFP15 showed association with high Ki67 (p &lt; 0.05), and no correlations were found with HER2 expression. Conclusion: In this cohort, GATA3 was the most sensitive single marker. The addition of MMG and SOX10 increases the sensitivity for detection of ER positive and ER negative breast cancers, respectively. These findings support the use of a combination of GATA3/MMG/SOX10 for confirmation of metastatic breast cancer.

Gastric aspiration in sudden unexpected infant death of Prader–Willi syndrome: immunohistochemical detection of feeding components

Prader–Willi syndrome (PWS) in infants is characterized by hypotonia and poor sucking with feeding difficulties. Two autopsy cases of sudden unexpected death during sleep after tube feeding are described herein. For one, gastric aspiration caused by the possible milk regurgitation was suspected. Immunohistochemical examination of lung sections was performed using three antibodies to human α-lactalbumin, human gross cystic disease fluid protein 15, and cow whey β-lactoglobulin. Five cases of sudden unexpected infant death occurring earlier than at 6 months old were selected as controls. Marked immune-staining for infant formula in one PWS subject was evident within terminal bronchioles and alveoli with granular and amorphous features. However, no positive staining was apparent in the other subject, who exhibited contrasting features in milk distribution. Among control cases, one showed mild staining in the bronchiole, but the others did not. The antibody to β-lactoglobulin reacted specifically with formula, with no nonspecific background. Gastric contents in the airway can be a difficult issue because of the consequent terminal gasping. However, because of an episode of antemortem symptoms of potential regurgitation, and from findings at autopsy such as petechiae, we inferred that fatal regurgitation occurred in this PWS infant after tube feeding. Several clinical reports have described milk aspiration, but this pathological report is the first related to aspiration in PWS during tube feeding.

Value of Proline, Glutamic Acid, and Leucine-Rich Protein 1 and GATA Binding Protein 3 Expression in Breast Cancer: An Immunohistochemical study

GATA binding protein 3 was more sensitive than traditional markers such as gross cystic disease fluid protein 15 and mammaglobin for identifying primary and metastatic breast carcinomas, but its significance decreased in triple-negative breast cancer. Recent studies showed a high expression rate of proline glutamic acid and leucine-rich protein in breast cancer and their superiority over GATA3 in triple-negative breast cancer. Our study provided new insights into the diagnostic and prognostic roles of PELP1 and GATA3 in primary and metastatic breast cancer. An immunohistochemical assay was carried out using PELP1 and GATA3 in 60 cases of primary breast cancer and 15 metastatic. Invasive carcinoma of no special type was the predominant type (80%). The majority of cases were grade 3 (68.3%). GATA3 expression was 83.3% positive in primary breast carcinomas and 73.5% positive in metastatic breast carcinomas. In comparison, PELP1 had a 96.7% positive expression rate in primary breast carcinomas and an 86.7% positive expression rate in metastasis. There was a statistically significant agreement between GATA3 and PELP1 in the diagnosis of the cases. PELP1 is a significantly higher proportion of both primary and metastatic breast carcinomas than GATA3. In breast cancer, there was a strong association between favorable prognostic factors and GATA3 expression, with evidence of an inverse association with Ki-67 overexpression.

Rectal Phenotype of Perianal Paget Disease: Rare Concomitant Phenomena.

Classically, 'Paget disease' refers to a distinct histological pattern in breast carcinoma. Here, we review the clinicopathological features of anorectal adenocarcinoma with 'pagetoid' spread. Histological and immunohistochemical records for 11 cases of anorectal adenocarcinoma with pagetoid spread among 958 Japanese patients with primary rectal/anal carcinoma were reviewed. Grossly, nine of 11 cases had areas of invasive carcinoma: Tubular adenocarcinoma in eight and neuroendocrine carcinoma in one. Pagetoid components were positive for cytokeratin 7 in eight cases, cytokeratin 20 and caudal type homeobox 2 in all 11 cases, and p63 in one case, but were negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), gross cystic disease fluid protein-15, and GATA binding protein 3. The prevalence of perianal Paget disease in this series was 1.1%, with two cases of genuine perianal Paget disease with a rectal phenotype without invasive carcinoma. The rectal phenotype of perianal Paget disease may not be associated with HER2 overexpression.

Intertumoral Heterogeneity of Primary Breast Tumors and Synchronous Axillary Lymph Node Metastases Reflected in IHC-Assessed Expression of Routine and Nonstandard Biomarkers

Breast cancer (BC) remains a significant healthcare challenge. Routinely, the treatment strategy is determined by immunohistochemistry (IHC)-based assessment of the key proteins such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. However, it is estimated that over 75% of deaths result from metastatic tumors, indicating a need to develop more accurate protocols for intertumoral heterogeneity assessment and their consequences on prognosis. Therefore, the aim of this preliminary study was the identification of the expression profiles of routinely used biomarkers (ER, PR, HER2, Ki-67) and additional relevant proteins [Bcl-2, cyclin D1, E-cadherin, Snail+Slug, gross cystic disease fluid protein 15 (GCDFP-15), programmed death receptor 1 (PD-L1), and phosphatase of regenerating liver 3 (PRL-3)] in breast primary tumors (PTs) and paired synchronous axillary lymph node (ALN) metastases. A total of 67 tissue samples met the inclusion criteria for the study. The expression status of biomarkers was assessed in PTs and ALN metastases using tissue microarrays followed by IHC. In 11 cases, the shift of intrinsic molecular BC subtype was noticed between PTs and paired ALN metastases. Moreover, a significant disproportion in E-cadherin presence (p = 0.0002) was noted in both foci, and the expression status of all proteins except for HER2 demonstrated considerable variance (k = 1, p < 0.0001). Importantly, in around 30% of cases, the ALN metastases demonstrated discordance, i.e., loss/gain of expression, compared to the PTs. Intertumoral synchronous heterogeneity in both foci (primary tumor and node metastasis) is an essential phenomenon affecting the clinical subtype and characteristics of BC. Furthermore, a greater understanding of this event could potentially improve therapeutic efficacy.

Hybrid Carcinoma of the Parotid Gland: An Extremely Rare Three Cases with an Immunohistochemical Analysis and a Review of the Literature

Salivary hybrid carcinoma (HC) is defined as when two or more kinds of carcinoma exist at the same location in a single mass. We reestimated and examined three cases of salivary gland HC. Case 1 involved a 76-year-old male. Case 2 involved a 74-year-old female. Case 3 involved a 66-year-old male. Histologically, case 1 involved a combination of salivary duct carcinoma (SDC) and squamous cell carcinoma (SqCC). Immunohistochemically, the former was positive for gross cystic disease fluid protein (GCDFP)-15 and androgen receptor (AR). Case 2 involved a combination of SqCC and neuroendocrine carcinoma. Immunohistochemically the latter was positive for synaptophysin and neural cell adhesion molecule (NCAM). Case 3 involved a combination of SDC and epithelial-myoepithelial carcinoma (EMC). Immunohistochemically, the former was positive for GCDFP-15 and AR, whereas the inner cells of the latter were positive for cytokeratin 7, and the outer cells of the latter were positive for actin. Because of the transitional zone between SDC and EMC, it was speculated that high-grade SDC arose from low-grade EMC.

α-Methylacyl-CoA racemase: a useful immunohistochemical marker of breast carcinoma with apocrine differentiation

Carcinoma with apocrine differentiation is an androgen receptor (AR)-positive subset of triple-negative breast carcinomas. In addition to carcinoma with apocrine differentiation, other AR-positive triple-negative breast carcinomas occur, albeit less frequently. We found that α-methylacyl-CoA racemase (AMACR), also known as P504S, is overexpressed in carcinoma with apocrine differentiation and non-neoplastic apocrine metaplasia. We aimed to evaluate AMACR as a possible marker of carcinoma with apocrine differentiation. We immunohistochemically examined the expression of AMACR in carcinoma with apocrine differentiation and nonapocrine carcinomas and compared it with that of gross cystic disease fluid protein-15 (GCDFP-15). In total, 212 breast carcinomas were evaluated: 39 carcinomas with apocrine differentiation, 28 ductal carcinomas in situ with apocrine morphology (ADCIS), and 145 nonapocrine breast carcinomas. AMACR was expressed in 38 of 39 (97.4%) carcinomas with apocrine differentiation and in 27 of 28 (96.4%) ADCIS, consistent with the expression of GCDFP-15. However, in nonapocrine carcinomas, AMACR expression was observed in 32 of 145 (22.0%) lesions, whereas GCDFP-15 expression was observed in 91 of 145 (62.7%) lesions. For carcinoma with apocrine differentiation, AMACR was as sensitive as GCDFP-15 (both 97.1%) but more specific (77.9% versus 37.2%). In selected cases, AMACR messenger RNA (mRNA) levels were quantitatively determined relative to that of TATA-binding protein mRNA, and they comprised 5.23, 1.33, and 0.60 for carcinomas with apocrine differentiation, nonapocrine carcinomas, and normal breast tissue, respectively. CONCLUSION: Our findings demonstrate that AMACR expression may be used for differentiating carcinoma with apocrine differentiation from nonapocrine carcinomas and indicate that AMACR is a more sensitive carcinoma with apocrine differentiation marker than GCDFP-15.