Cystic Disease Fluid Protein Research Articles

Evaluation of quantitative polymerase chain reaction markers for the detection of breast cancer cells in ovarian tissue stored for fertility preservation

To develop molecular tools increasing the sensitivity of breast cancer micrometastases detection within ovarian tissue cryopreserved for fertility preservation. Expression of breast markers was evaluated by quantitative polymerase chain reaction in ovarian tissue from patients with benign or cancerous diseases. Suspected tissues were long-term xenografted into mice. Academic research institute. Patients undergoing a fertility preservation procedure. Ovarian tissue was processed for RNA extraction and quantitative polymerase chain reaction analysis. Cryopreserved ovarian cortex from patients with breast cancer or benign disease was grafted for 6 months into severe combined immunodeficiency mice. Predictive values of mammaglobin 1 (MGB-1), gross cystic disease fluid protein-15 (GCDFP-15), small breast epithelial mucine (SBEM), and mammaglobin 2 (MGB-2) to detect breast cancer cells in ovarian tissue, and the potential development of cancerous disease after xenograft of ovarian cortex from breast cancer patients. MGB-1 and GCDFP-15 presented the highest predictive values to detect breast cancer micrometastases in the ovarian cortex, with an efficiency reaching 100% and 77%, respectively. The MGB-2 assay resulted in a high false-positive rate (47%) in the ovarian cortex but could be used to detect breast cancer cells in ovarian medulla. MGB-1 was detected in three of five ovarian cortex samples from early-stage breast cancer patients but not in the ovarian tissue from advanced breast cancer patients (none of 10). None of the mice grafted with ovarian tissue expressing these markers developed cancerous disease. MGB-1, GCDFP-15, and MGB-2 can serve as molecular markers for the detection of breast cancer micrometastases within the ovarian tissue of breast cancer patients. However, the clinical relevance of such a highly sensitive assay must be further investigated.

Breast carcinoma metastasis to the lacrimal gland: Two case reports.

A 77-year-old female, with proptosis, reduced eye motility and diplopia which had developed over two to three months and a 69-year-old female with proptosis, oedema of the eyelid, reduced motility and ptosis, which had developed over three weeks, are presented in the present study. Computed tomography scans revealed irregular lacrimal gland tumours in the two patients. The two patients had history of breast cancer. The first breast cancer metastasis in the lacrimal gland demonstrated a cribriform growth pattern containing ductal elements. The epithelial tumour cells stained positive for cytokeratin (1-8, 10, 14-16, 18 and 19), oestrogen receptor, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and gross cystic disease fluid protein 15 (GCDFP-15). The second metastatic tumour was positive for EMA and estrogen receptor, but variably positive for CEA and GCDFP-15. The metastasis in the lacrimal gland was a pleomorphic tumour. The tumour cells were positive for EMA and variably positive for oestrogen and CEA. Metastases to the lacrimal gland are extremely rare, and metastases to the lacrimal gland should be considered in the diagnoses of lacrimal gland tumours. The present study aimed to describe two such cases and draw attention to breast carcinomas as a differential diagnosis and the most frequent cause of lacrimal gland metastasis.

Abstract P3-04-07: Androgen receptor expression in triple negative breast cancer

Abstract Background: Patients with androgen receptor (AR) positive triple-negative breast cancer (TNBC) may derive a significant benefit from anti-androgen therapy. While AR positivity is often defined by protein expression by immunohistochemistry (IHC), the benefit of anti-androgen therapy in patients who have the Luminal Androgen Receptor (LAR) molecular subtype as defined by genomic profiling is unclear. Our aim was to study the clinical, pathologic and molecular profiles of AR+ tumors by IHC in a diverse set of TNBC. Methods: Tissue microarrays from two separate, well-annotated institutional cohorts (Case Western Reserve University, Yale University) of early-stage TNBC were evaluated for AR expression by IHC (clone SP107, Ventana Benchmark Ultra). AR positivity was defined as greater than or equal to 10% staining in tumor nuclei. AR expression was correlated with clinical and pathologic features such as age, race, grade, and stage within and between the two cohorts. Gene expression was analyzed with the DASL assay (Illumina) on RNA extracted from formalin-fixed paraffin-embedded material using the Ambion RecoverAll kit (Applied Biosystems AM1975). Pietenpol TNBC molecular subtypes were calculated using the online TNBC type tool. Co-expression of AR with other hormone-related proteins including gross cystic disease fluid protein-15 (GCDFP-15, clone EP1582Y, Ventana Benchmark Ultra) and GATA transcription factor 3 (GATA3, clone L50-823, Bondmax Leica) were also assessed. Results: Overall, 22% of cases (n=192) were AR+ by IHC. There was no association between AR expression and age, race, grade or stage within or between the two cohorts. Gene expression data was available on 88 tumors with AR staining results and demonstrated that AR positivity by IHC was not exclusive for the TNBC LAR molecular subtype. Three of five (3/5) tumors that were classified and LAR were in fact AR+ by IHC. Tumors that were AR+ by IHC were also identified in the basal-like 2 (BL2), mesenchymal stem-like (MSL), immunomodulatory (IM), and unstable molecular TNBC categories with low frequency. Notably, of cases that were rejected as ER+ by gene expression profiling despite being clinically TNBC, three of five (3/5) were in fact AR+ by IHC. Examination of other hormone-related proteins in a subset of these patients revealed that AR expression was significantly associated with GCDFP-15 expression (p=0.0007) and was borderline significant for GATA3 expression (p=0.068). Conclusions: AR protein expression levels by IHC were similar in two separate institutional archival cohorts of TNBC and did not correlate with age, race, grade or stage. Comparison of AR IHC data with genomic data suggests that the AR+ phenotype is not unique to LAR subtype of TNBC by gene expression profiling. AR protein expression may be seen in clinically TNBC patients who have a more luminal subtype as evidenced by co-expression of GCDFP-15 and GATA3. Our results suggest that AR staining by IHC may be necessary to capture all patients who may benefit from anti-androgen therapy. Citation Format: Hannah Gilmore, Vinay Varadan, Nicole Williams, Cheryl L Thompson, Stephanie Kim, Peter Hsu, Kristy Miskimen, Aditi Palkar, Shaveta Vinayak, Robert Lindner, Lyndsay Harris. Androgen receptor expression in triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-04-07.

Gross cystic disease fluid protein 15 in stratum corneum is a potential marker of decreased eccrine sweating for atopic dermatitis.

It is well known that eccrine sweating is attenuated in patients with atopic dermatitis (AD). We have reported by using proteome analysis that gross cystic disease fluid protein 15 (GCDFP15), a substance secreted from eccrine sweat glands, is decreased in tape-stripped stratum corneum (SC) samples from AD patients. The aim of this study was to evaluate GCDFP15 production by eccrine glands with SC samples and to assess sweating in AD. SC samples were obtained from 51 healthy control (HC) and 51 AD individuals. Sweat samples were from 18 HC and 12 AD subjects. GCDFP15 was quantified by ELISA. By immunohistochemistry, the expression of GCDFP15 in eccrine glands was examined in normal and AD skin specimens. To identify GCDFP15-producing cells, double immunofluorescence staining for GCDFP15 and S100 protein was performed in frozen sections. To address the mechanism underlying the decreased eccrine sweating in AD patients, we examined the expression of cholinergic receptor M3 (CHRM3), a receptor for acetylcholine-induced sweating, in eccrine sweat glands. The amounts of GCDFP15 in the SC extracts were significantly lower in AD than HC (P < 0.0001). The sweat samples from AD patients also had lower levels of GCDFP15 concentration (P < 0.05). Immunohistochemistry showed positive GCDFP15 staining in the eccrine gland secretory cells and the ductal and acrosyringial lumen in normal skin, but AD lacked clear staining. Immunofluorescence staining revealed that GCDFP15 was co-expressed with S100 protein, suggesting that the clear cell of eccrine glands produces GCDFP15. Finally, we found that the expression of CHRM3 was depressed in AD, suggesting contribution to the low sweating. The SC of AD patients contains a low amount of GCDFP15 due to both low sweating and low GCDFP15 concentration in the sweat. GCDFP15 in SC is a potential marker for dysregulated sweating in AD.

GATA-binding protein 3 enhances the utility of gross cystic disease fluid protein-15 and mammaglobin A in triple-negative breast cancer by immunohistochemistry.

We have demonstrated previously that gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin A (MAM) are of limited utility in triple-negative breast cancer (TNBC). GATA-binding protein 3 (GATA-3) is an emerging breast-associated immunohistochemical (IHC) marker with limited data in TNBC. Here, we examined GATA-3 expression in TNBC in comparison with GCDFP-15 and MAM. We studied GATA-3, GCDFP-15 and MAM IHC expression in 62 primary and 68 metastatic TNBCs. In primary TNBCs, GATA-3 staining was observed in 25 cases (40%), including 16 cases that were negative for GCDFP-15 and MAM. In metastatic TNBCs, GATA-3 staining was observed in 30 cases (44%), including 16 cases that were negative for GCDFP-15 and MAM. The expression frequency of any of the markers was 56% in primary and 62% in metastatic TNBCs. However, when focal staining was excluded, the expression frequency of any marker dropped to 31% and 44%, respectively. GATA-3 is expressed at a higher frequency by IHC in TNBC compared to GCDFP-15 and MAM, although the tissue specificity of the latter markers may be superior. When evaluating a triple-negative tumour, including GATA-3 in a panel of markers may increase the diagnostic accuracy for tissue origin in the appropriate clinical setting.

Solitary uterine metastasis of invasive lobular carcinoma after adjuvant endocrine therapy: a case report

IntroductionSolitary uterine metastases from extragenital cancers are very rare. Breast cancer is the most frequent primary site of metastasis to the uterine corpus, with invasive lobular carcinoma more likely to spread to gynecologic organs than invasive ductal carcinoma.Case presentationA 62-year-old postmenopausal Japanese woman was diagnosed with uterine leiomyomata more than 20 years ago and had been managed conservatively until menopause. Seven years prior to her presentation, she was diagnosed with breast cancer and underwent a partial resection of her right breast for stage IIA invasive lobular carcinoma. She underwent adjuvant chemotherapy, radiotherapy, and five years of anastrozole hormonal therapy. She presented with a growing uterine mass. Her tumor marker levels were markedly increased over the course of her follow-up, but a systemic examination revealed only a solitary uterine tumor. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. A histopathological examination, including detailed immunohistochemistry, confirmed metastatic invasive lobular carcinoma, infiltrating both her uterine myometrium and fibroid tissue.ConclusionWe report a very rare metastatic pattern of invasive lobular carcinoma and demonstrate that gross cystic disease fluid protein-15 and mammaglobin are useful in the diagnosis of metastatic breast cancer.

Utility of GATA3, mammaglobin, GCDFP-15, and ER in the detection of intrathoracic metastatic breast carcinoma

Breast carcinoma (BC) metastatic to the intrathoracic cavity is difficult to diagnose due to low sensitivity of current immunohistochemical (IHC) stains. Mammaglobin, gross cystic disease fluid protein-15 (GCDFP-15), and estrogen receptor (ER) immunomarkers show variable results. GATA3 is a recently described marker for detecting urothelial and breast cancers. Our goal is to test the utility of GATA3 in cell blocks from thoracic cytology specimens. We retrieved cases of BC that metastasized to the thoracic cavity from January 1, 2005 to September 30, 2013. IHC was performed on the cell blocks for the presence of GATA3, ER, GCDFP-15, and mammaglobin. Stains were scored quantitatively and qualitatively. Fifty cases of metastatic BC found in pleural effusions and endobronchial ultrasound-guided fine-needle aspirates were identified in 48 patients. Thirty-four cases had sufficient material for IHC (19 pleural effusions, 15 endobronchial ultrasound-guided fine-needle aspirates). GATA3 showed strong nuclear positivity in 31 of 34 cases (91.2%). ER (25 of 34, 73.5%), mammaglobin (23 of 34, 67.6%) and GCDFP-15 (11 of 34, 32.6%) were positive in fewer cases. GATA3 and ER were concordant in 26 of 34 cases (76.5%) (24 ER/GATA3-positive, 2 ER/GATA3-negative). Discordant results were found in 8 of 34 cases (23.5%). Of these, GATA3 was positive and ER was negative in 7 cases. GATA3 was negative and ER was positive in 1 case. GATA3 is more sensitive than ER, mammaglobin, or GCDFP-15 in detecting metastatic BC in cytologic specimens. GATA3 may be positive when ER is negative. In cytologic specimens with limited diagnostic material, GATA3 may be used as a first-line marker in a limited IHC panel to support metastatic BC.

GATA-binding protein 3, gross cystic disease fluid protein-15 and mammaglobin have distinct prognostic implications in different invasive breast carcinoma subgroups.

To evaluate the prognostic significance of GATA-binding protein 3 (GATA-3), gross cystic disease fluid protein-15 (GCDFP-15) and mammaglobin (MGB) in invasive breast carcinomas (IBCs). GATA-3, GCDFP-15 and MGB were expressed in 37.9% (370/976), 26.0% (254/978) and 35.3% (348/986) of this cohort of 1017 IBCs, respectively. GCDFP-15 was an independent favourable prognostic factor in all cases [disease-free survival (DFS), hazard ratio (HR) 0.587, P=0.049; overall survival (OS), HR 0.512, P=0.049], as well as in oestrogen receptor (ER)-negative (DFS, HR 0.353, P=0.012; OS, HR 0.310, P=0.017) and HER2-positive (DFS, HR 0.279, P=0.036; OS, HR 0.235, P=0.050) cases; it also refined the prognostication of molecular apocrine cancers. GATA-3 and MGB did not show any prognostic significance. The commonly used breast carcinoma biomarkers vary in their prognostic implications. GCDFP-15 independently indicated a favourable prognosis, especially in ER-negative, HER2-positive and molecular apocrine cancers. GATA-3 and MGB were not associated with outcome.

Cutaneous Metastasis of Gastric Cancer Mimicking Primary Inflammatory Breast Cancer.

Dear Editor: Although gastric cancer is one of the most common cancers in Korea, cutaneous metastasis is rarely reported, and the reported incidence of cutaneous metastasis of gastric cancer was 0.19% in a single Korean hospital1. In a clinicopathological analysis of 27 patients with cutaneous metastasis of gastric cancer, Kim et al.1 reported that the most common site was the abdomen (33.3%), and the most common clinical finding was a nodular lesion (55.6%), followed by an inflammatory lesion (25.9%). Herein, we report a rare case of cutaneous metastasis of gastric cancer mimicking primary inflammatory breast cancer. A 55-year-old woman was referred for an erythematous patch with swelling on the left breast for 2 months. She denied any trauma history. Physical examination revealed a diffuse patch with tenderness and a small, round, blue nodule (Fig. 1). There was no other palpable nodule in both the breasts and in the axillae. Fourteen years previously, she had a diagnosis of advanced gastric cancer and underwent distal gastrectomy. Relapse of gastric cancer was diagnosed through peritoneal biopsy 2 years before her presentation to our department, and she then received chemotherapy. Her response to chemotherapy was poor, and when she was referred to our department, a tumor was found to be disseminated in the pleural fluid and peritoneum, as confirmed on peritoneal biopsy and pleural fluid cytology. Ultrasonography, chest computed tomography, and mammography of the left breast showed no definite mass or microcalcification. Histopathological findings showed a poorly differentiated carcinoma with prominent lymphovascular invasion. Immunohistochemical examination showed that the cells were positive for carcinoembryonic antigen and cytokeratin (CK)-7 but negative for CK-20, gross cystic disease fluid protein-15 (GCDFP-15), estrogen receptor (ER), and progesterone receptor (PR) (Fig. 2). On the basis of these clinical and histological findings, cutaneous metastasis of gastric cancer was diagnosed. She then received radiotherapy to the left breast. Fig. 1 A diffuse, erythematous swelling and a small, round, blue nodule on the left breast. Fig. 2 (A, B) Histopathological findings showed poorly differentiated carcinoma with prominent lymphovascular invasion (HE A: ×40, B: ×100). Immunohistochemical examination showed that the cells were positive for carcinoembryonic antigen ... There are only a few reports on cutaneous metastasis of breast cancer mimicking primary inflammatory breast cancer, and among those cases, seven originated from gastric cancer2,3,4. Differential diagnosis of primary and metastatic adenocarcinoma of the breast represents a clinical challenge3. Although some gastric cancers have similar patterns of CK staining, breast adenocarcinoma cells are positive for CK-7 but negative for CK-20. ER, PR, and GCDFP-15 are frequently expressed in primary breast adenocarcinoma, whereas for the absence of all three proteins on staining is specific for gastric adenocarcinoma2. The direct spread of tumor cells through dermal lymphatic vessels could cause inflammatory changes in the skin, which are found in both primary and metastatic inflammatory carcinomas2,5. In addition, clinical findings of inflammatory breast cancer can lead to misdiagnosis of acute mastitis, especially in patients with no history of malignant disease5. Most reported cases of breast metastasis were found to have nodules that are suggestive of a benign tumor2. However, in our case, there was no definite nodule on radiologic findings, suggesting metastasis. Despite the negative findings on imaging evaluations, dermatologists should be aware of the possibility of breast metastasis, especially in patients with a history of malignant disease.

Cancer of Unknown Primary Site: Not All is Lost!

A Cancer of Unknown Primary Site (CUPS) is defined as a metastatic tumor for which the site of origin remains unknown after establishing tissue diagnosis despite a standard diagnostic approach. It is still not known whether CUP is an entity with dormancy of primary as its hallmark or a distinct entity with specific genetic aberrations which define it as a primary metastatic disease. It poses a diagnostic challenge to the pathologists and often poses a therapeutic dilemma for the oncologists. The diagnostic algorithm includes; age, gender, histology, site of metastasis, distribution and natural history of disease, and expression of tissue specific markers by the malignant clones as revealed on immunostains, e.g. TTF1 for thyroid gland and adenocarcinoma lung, PSA for prostate gland, estrogen/ progesterone receptors and gross cystic disease fluid protein-15 for breast cancer, etc. Despite extensive and expensive diagnostic work up, in almost 20-45% cases the site of their origin remains unknown, however the yield rises to 70-80% after postmortem examination. While the pathology teams are working to resolve the primary site, the oncology teams are adamant on identifying subset of patients that may be treatable and potentially curable. However, CUPS remains aggressive, and generally associated with a poorer prognosis with a median survival of less than a year. The review focuses on current practices in diagnoses and treatment of an occasionally rare, and a challenging entity.

Gross cystic disease fluid protein-15/prolactin-inducible protein as a biomarker for keratoconus disease.

Keratoconus (KC) is a bilateral degenerative disease of the cornea characterized by corneal bulging, stromal thinning, and scarring. The etiology of the disease is unknown. In this study, we identified a new biomarker for KC that is present in vivo and in vitro. In vivo, tear samples were collected from age-matched controls with no eye disease (n = 36) and KC diagnosed subjects (n = 17). Samples were processed for proteomics using LC-MS/MS. In vitro, cells were isolated from controls (Human Corneal Fibroblasts-HCF) and KC subjects (Human Keratoconus Cells-HKC) and stimulated with a Vitamin C (VitC) derivative for 4 weeks, and with one of the three transforming growth factor-beta (TGF-β) isoforms. Samples were analyzed using real-time PCR and Western Blots. By using proteomics analysis, the Gross cystic disease fluid protein-15 (GCDFP-15) or prolactin-inducible protein (PIP) was found to be the best independent biomarker able to discriminate between KC and controls. The intensity of GCDFP-15/PIP was significantly higher in healthy subjects compared to KC-diagnosed. Similar findings were seen in vitro, using a 3D culture model. All three TGF-β isoforms significantly down-regulated the expression of GCDFP-15/PIP. Zinc-alpha-2-glycoprotein (AZGP1), a protein that binds to PIP, was identified by proteomics and cell culture to be highly regulated. In this study by different complementary techniques we confirmed the potential role of GCDFP-15/PIP as a novel biomarker for KC disease. It is likely that exploring the GCDFP-15/PIP-AZGP1 interactions will help better understand the mechanism of KC disease.

Proteome analysis of stratum corneum from atopic dermatitis patients by hybrid quadrupole-orbitrap mass spectrometer

Proteome analysis of stratum corneum from atopic dermatitis patients by hybrid quadrupole-orbitrap mass spectrometer

Abstract 2488: Analysis of the salivary proteome of the prolactin-inducible-protein knockout mouse

Abstract The human Prolactin-Inducible-Protein (PIP)/Gross Cystic Disease Fluid Protein 15 (GCDFP-15) gene is abnormally expressed in human invasive breast cancer and gross cystic disease of the breast. In healthy individuals PIP is highly expressed in salivary, sweat and lacrimal glands, and the secreted protein abundantly found in saliva as well as other bodily fluids which bathe various ports of entry. PIP has been shown to bind numerous bacterial strains as well as a number of immunoregulatory molecules including the CD4-T cell receptor and IgG and is therefore implicated to play an immune role in host defense. In the present study we interrogated the salivary proteome of the PIP knockout (Pip KO) mouse by mass spectrometry to determine protein changes that occur in saliva in the absence of PIP. Proteomic analysis identified 165 proteins in the mouse saliva which had a minimum of 2 unique peptides at the 99% confidence level. Nineteen proteins, including 2 proposed markers of disease, S100A9 and adenosine deaminase, were significantly differentially expressed in the saliva of the Pip KO mouse, compared to the saliva of the wild type counterparts. Functional and biological determinations revealed that the differentially expressed proteins were associated with processes that include inflammatory responses, immunity and cell death. This study provides evidence that a number of proteins associated with host defense are affected by the loss of PIP, and lends support for an immunomodulatory role for PIP. Citation Format: Anne Blanchard, Peyman Ezzati, Xiuli Ma, John Wilkins, Yvonne Myal. Analysis of the salivary proteome of the prolactin-inducible-protein knockout mouse. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2488. doi:10.1158/1538-7445.AM2014-2488

A comparative immunohistochemistry study of diagnostic tools in salivary gland tumors: usefulness of mammaglobin, gross cystic disease fluid protein 15, and p63 cytoplasmic staining for the diagnosis of mammary analog secretory carcinoma?

Mammary analog secretory carcinoma (MASC) of the salivary gland has been recently described according to morphological, immunohistochemical, and molecular (ETV6-NTRK3 translocation) similarities with the mammary secretory carcinoma. The most important differential diagnostic considerations of MASC are low-grade adenocarcinoma not otherwise specified (NOS), cystadenocarcinoma, and acinic cell carcinoma (AciCC). These tumors may share an overlapping morphology with MASC, and additional immunohistochemical studies are required to reinforce the diagnosis. Mammaglobin, GCDFP-15, and p63 staining have been reported in MASC. Our study was designed to check the specificity of these antibodies in MASC compared to other frequent tumors of salivary glands. A series of 62 salivary gland tumors [10 MASCs, 5 adenocarcinomas NOS and 2 cystadenocarcinomas with MASC features and without ETV6 rearrangement, one low-grade cribriform cystadenocarcinoma (LGCCC), 9 AciCCs, 10 MECs, 10 adenoid cystic carcinomas (AdeCCs), 5 polymorphous low-grade adenocarcinomas (PLGAs), and 10 pleomorphic adenomas (PAs)] was analyzed by immunohistochemistry with mammaglobin, GCDFP-15, and p63 antibodies. Positivity for mammaglobin was observed in all MASCs, cystadenocarcinomas, LGCCC, and PLGAs, in some adenocarcinomas NOS, PAs, and MECs, rarely in AciCCs and never in AdeCCs. Positivity for GCDFP-15 was observed in most of the tumor types except in AdeCCs. Interestingly, cytoplasmic positivity for p63 was observed in most of MASCs and PLGAs while rarely in adenocarcinomas NOS and PAs, and never in the other tumor types. Our study revealed the usefulness of mammaglobin and p63 cytoplasmic staining to define which tumors are worth to be screened for ETV6 rearrangement.

Breast as an unusual site of metastasis- series of 3 cases and review of literature.

Background and objectives Metastasis to the breast from extra mammary sites is uncommon with an incidence ranging from 1.2 to 2% in clinical reports. Approximately 300 cases of breast metastasis from extra mammary sites have been reported, mostly in small series or as a single case report. Gastrointestinal adenocarcinoma metastasising to the breast is also very rare and only 30 cases have been reported in the literature. Metastatic deposits within the breast may be difficult to distinguish from primary breast carcinoma. Radiological features and immunohistochemistry especially for steroid hormone receptors (ER/PR) and expression of gross cystic disease fluid protein (GCDFP) and presence of other immunohistochemistry protein factors in breast metastasis which are specific to primary site may be helpful in differentiating these two conditions. Materials and methods In this series of 3 cases of breast as an unusual site of metastasis, we present different cases of adenocarcinoma of stomach, sigmoid colon and kidney with metastasis to the breast and discuss the differential diagnosis and management plans. Conclusion In conclusion, secondary tumors to the breast are rare and thus differentiating primary tumors from metastatic breast carcinoma is important for rational and optimum therapy and avoidance of unnecessary radical surgery. Palpable breast lump without typical radiological signs of primary breast carcinoma in patients with known primary should be suspected of representing metastasis.

Immunohistochemical Evaluation of GATA-3 Expression in ER-Negative Breast Carcinomas

Estrogen receptor (ER), gross cystic disease fluid protein 15 (GCDFP-15), and mammaglobin (MGB) are commonly used breast-specific immunomarkers; however, about half of metastatic breast carcinomas are negative for all three. GATA-binding protein 3 (GATA-3) has emerged recently as a sensitive and relatively specific immunomarker for breast and urothelial carcinomas, but the data documenting its expression in ER-negative breast carcinomas are limited; this often poses a dilemma in the setting of metastases. The purpose of this study is to investigate expression of GATA-3 in ER-negative breast carcinomas. Immunohistochemical evaluation of GATA-3, GCDFP-15, and MGB on 96 ER-negative breast carcinomas was performed. Overall, 69% (66/96), 15% (14/96), and 35% (34/96) of ER-negative breast carcinomas expressed GATA-3, GCDFP-15, and MGB, respectively. Our data suggest that GATA-3 is, so far, the best breast-specific immunomarker, especially when encountering ER-negative metastatic breast carcinomas. GATA-3 should be included in the panel of immunomarkers in the workup of tumors of unknown primary.

Invasive extramammary Paget's disease of the bladder diagnosed 18 years after noninvasive extramammary Paget's disease of the vulva

Paget's disease of the vulva is a rare vulvar neoplasm most commonly seen in postmenopausal women. Clinically, it presents as a pink eczematoid lesion with white islands of hyperkeratosis accompanied by pruritus. Pathologically it resembles mammary Paget's disease of the nipple and areola, first described by Sir James Paget in 1874 (Paget). The mean age at diagnosis of Paget's disease of the vulva has been reported to be between 50 and 80 years, and it is most common in Caucasian women (Preti et al., 2000). Disease is often limited to the epidermis and mucosa, without invasion. The optimal management of Paget's disease of the vulva remains unclear. Surgical excision is usually the primary therapy; however, 30% to 60% of patients develop recurrent disease. Furthermore, the lesions often extend past clinically apparent borders and surgical excision is limited by the anatomy of the vulva. In addition, the disease is often multifocal. Immunohistochemistry (IHC) can help distinguish Paget's disease from other vulvar conditions. Cytokeratin 7 (CK7), cytokeratin 20 (CK20), carcinoembryonic antigen (CEA), and gross cystic disease fluid protein-15 (GCDFP-15) are common markers for Paget's disease. Approximately 10% of patients with Paget's disease of the vulva have an underlying second malignancy. These include colorectal cancer, cervical cancer, breast cancer, as well as carcinoma of the transitional epithelium from the renal pelvis to urethra. Routine screening with colonoscopy, Pap test, and mammogram is therefore recommended. In addition, in rare instances, Paget's disease may become invasive, infiltrating the dermis and even metastasizing to lymph nodes and distant sites (Reddy et al., 2012). In this report, we describe the case of a woman with noninvasive Paget's disease of the vulva who developed invasive Paget's disease of the bladder 18 years after her original diagnosis of Paget's disease of the vulva.

Primary Adenoid Cystic Carcinoma of the Skin Metastatic to the Lymph Nodes

Primary cutaneous adenoid cystic carcinoma (PCACC) is a rare adnexal skin tumor first described in 1975, of which merely 62 cases have so far been studied in detail and reported in the English literature. PCACC is usually regarded as apocrine in origin/differentiation, but its precise histogenesis is still not well known. PCACC has in most cases a rather indolent course but can produce local recurrences and, more rarely, regional (lymph node) and distant (pulmonary) metastases. We report herein a Greek woman with a long-standing PCACC that grew slowly over several years and produced metastasis in the regional lymph nodes, highlighting the potentially aggressive course of this tumor. The primary and metastatic tumors were studied immunohistochemically and proved to express several (sweat gland-related) antigens (such as keratin 7, epithelial membrane antigen, CD10, and CD117) but neither hormonal receptors nor p63 or Gross Cystic disease Fluid Protein 15. The salient clinicopathologic features of this rare cutaneous adnexal tumor are reviewed.

GATA3: A promising marker for metastatic breast carcinoma in serous effusion specimens

The usefulness of GATA3 (GATA-binding protein 3 to DNA sequence [A/T]GATA[A/G]) as a marker for metastatic breast carcinoma in serous effusion specimens was investigated. Cell block sections from 74 serous effusion specimens (32 ascitic, 2 pericardial, and 40 pleural fluids) were stained with an anti-GATA3 murine monoclonal antibody. The specimens included 62 confirmed metastatic carcinomas from the breast (30 specimens), female genital tract (13 specimens), gastrointestinal tract (7 specimens), lung adenocarcinoma (9 specimens), pancreas (1 specimen), kidney (1 specimen), and bladder (1 specimen). The breast carcinoma cases included 15 ductal carcinomas and 8 lobular carcinomas; the histology subtype was not available for 7 specimens. Twelve cases containing florid reactive mesothelial cells were also stained. The breast carcinoma cases were also stained for mammaglobin and gross cystic disease fluid protein of 15 kilodaltons (GCDFP-15) to compare their sensitivity with GATA3. Positive nuclear staining for GATA3 was found to be present in 90% of metastatic breast carcinoma specimens (27 of 30 specimens). All nonbreast metastatic carcinomas tested were negative with the exception of the single case of metastatic urothelial carcinoma. No staining was observed in any of the benign reactive cases or in benign mesothelial cells present in the malignant cell block preparations. Two cases demonstrated weak positivity of benign lymphoid cells. Staining results were unambiguous because all positive cases demonstrated intense nuclear staining in > 50% of tumor cells. Mammaglobin (57% staining; 17 of 30 cases) and GCDFP-15 (33% staining; 10 of 30 cases) were found to be less sensitive markers of breast carcinoma. If used in a panel, mammaglobin and GCFP-15 staining would have identified only 1 additional case compared with those stained with GATA3. GATA3 may be a useful addition to immunostaining panels for serous effusion specimens when metastatic breast carcinoma is a consideration.

Salivary duct carcinoma with rhabdoid features: Report of 2 cases with immunohistochemical and ultrastructural analyses

BackgroundSalivary duct carcinoma with rhabdoid features is extremely rare.MethodsWe report 2 cases of salivary duct carcinoma with rhabdoid features treated at our institution.ResultsCase 1 was a 44-year-old Japanese man who had swelling in the left parotid region. This tumor consisted of residual pleomorphic adenoma and widely invasive carcinoma, which showed a diffuse growth pattern by atypical rhabdoid cells. Case 2 was a 66-year-old Japanese man who had swelling of the right cervical region. This submandibular tumor was also composed of both residual pleomorphic adenoma region and invasive adenocarcinoma components, whereas some metastatic lesions were purely composed of rhabdoid cells. Such cells were strongly and diffusely positive for cytokeratins (CKs), gross cystic disease fluid protein-15 (GCDFP), and androgen receptor (AR). Case 1 was also positive for Her-2 and p53.ConclusionBoth patients were diagnosed with carcinoma ex pleomorphic adenoma and their carcinomatous components were composed of salivary duct carcinoma with rhabdoid features, which is a highly aggressive tumor, similar to salivary duct carcinoma. © 2013 The Authors. Head & Neck published by Wiley Periodicals, Inc. Head Neck 36: E28–E35, 2014