Apolipoprotein D is the major protein component in cyst fluid from women with human breast gross cystic disease.
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ABSTRACT:
SUBMITTER: Balbin M
PROVIDER: S-EPMC1149635 | biostudies-other | 1990 Nov
REPOSITORIES: biostudies-other
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Project description:Gross cystic disease fluid protein 15 (GCDFP-15), which is regulated by the androgen receptor (AR), is a diagnostic marker for mammary differentiation in histopathology. We determined the expression of GCDFP-15 in breast cancer subtypes, its potential prognostic and predictive value, as well as its relationship to AR expression.602 pre-therapeutic breast cancer core biopsies from the phase III randomized neoadjuvant GeparTrio trial (NCT00544765) were investigated for GCDFP-15 expression by immunohistochemistry. Expression data were correlated with disease-free (DFS) and overall survival (OS) time as well as pathological complete response (pCR) to neoadjuvant chemotherapy.239 tumors (39.7%) were GCDFP-15 positive. GCDFP-15 expression was positively linked to hormone receptor (HR) and HER2 positive tumor type, while most triple negative carcinomas were negative (p?<?0.0001). GCDFP-15 was also strongly correlated to AR expression (p 0.001), and to the so-called molecular apocrine subtype (HR-/AR+, p?<?0.0001). Higher rates of GCDFP-15 positivity were seen in tumors of lower grade (<0.0001) and negative nodal status (p?=?0.008). GCDFP-15 positive tumors tended to have a more favourable prognosis than GCDFP-15 negative tumors (DFS (p?=?0.052) and OS (p?=?0.044)), which was not independent from other factors in multivariate analysis. GCDFP-15 expression was not linked to pCR. Histological apocrine differentiation was frequent in molecular apocrine carcinomas (60.7%), and was associated with GCDFP-15 within this group (p?=?0.039).GCDFP-15 expression is higher in tumors with favorable prognostic features. GCDFP-15 expression is further a frequent feature of AR positive tumors and the molecular apocrine subtype. It might have reduced sensitivity as a diagnostic marker for mammary differentiation in triple negative tumors as compared to HR or HER2 positive tumor types.
| S-EPMC4122770 | biostudies-literature
Project description:Echinococcus granulosus infection causes cystic echinococcosis (CE); the generation of liver fibrosis around the parasitic larval cyst (metacestode) may play a major role in the spontaneous limitation of the parasitic growth; however, fibrogenesis has received little attention in CE. It has been reported that miR-19b plays a role in various diseases, including infectious diseases, by regulating fibrogenesis. However, its function in the development of liver fibrosis in E. granulosus infection is unknown.The expression of miR-19b and genes that are involved in liver fibrosis were analysed in E. granulosus-infected human livers using qRT-PCR. The role of miR-19b on hepatic stellate cells (LX-2 cells in vitro) treated with hydatid cyst fluid (HCF) was then analysed by 3-(4, 5-dimet-hylthiazol-2-yl)-2, 4-diphenyl-tetrazolium bromide (MTT) assay, qRT-PCR, Western blot and flow cytometry.The results showed that the expression of miR-19 was significantly reduced in the pericystic collagen-rich liver tissue of CE patients, compared to normal liver. Incubation of LX-2 cells (in vitro) with HCF induced a decreased proliferation of these cells and a reduced expression of miR-19, inversely correlated with the expression of collagen 1A1 and TGF-? receptor II (T?RII). Conversely, overexpression of miR-19 by LX-2 cells inhibited the proliferation of these cells and led to decreased T?RII expression.Our study provides new evidence for the intervention of miRNAs in the regulation of fibrosis in infectious diseases; it suggests that E. granulosus can inhibit miR-19 liver expression and promote fibrosis through the increase in T?RII, the activation of hepatic stellate cells and extracellular matrix production.
| S-EPMC4866024 | biostudies-literature
Project description:BACKGROUND:Gross cystic disease fluid protein-15(GCDFP-15)/prolactin-inducible protein (PIP) is a secretory acinar glycoprotein of 14 KDa which we have recently described as significantly lower in salivary samples of patients with primary Sjögren's syndrome (pSS) in comparison to healthy volunteers by proteomic analysis. AIMS OF THE STUDY:(1) to validate our previous data on the decrease of GCDFP-15/PIP protein in a larger number of subjects with pSS (2) to integrate the proteomic results with complementary immunoassays in order better clarify the pathophysiological relevance of GCDFP-15/PIP in pSS exocrinopathy (3) to assess both the glandular expression of the GCDFP-15/PIP and the levels of glandular GCDFP-15/PIP mRNA in the patients' minor salivary gland (MSG) biopsies in order to verify whether the observed reduction of GCDFP-15/PIP in saliva may be related to a decrease in the protein production. PATIENTS AND METHODS:A total of 123 salivary samples from patients affected by pSS, no-SS sicca syndrome and sex- age-matched healthy volunteers were analyzed by different proteomic techniques (SELDI-TOF-MS, 2DE, MALDI-TOF-MS). The expression of GCDFP-15/PIP was then validated by western blot analysis. Real Time PCR and immunohistochemistry for GCDFP-15/PIP in the minor salivary glands (MSG) biopsies were then carried out. RESULTS:By using complementary proteomic analysis we found that a putative peak of 16547 m/z was among the best independent biomarkers for pSS able to discriminate between patients and healthy controls with a sensitivity of 96 % and a specificity of 70%, with a global cross validated error of 29%. We identified the peak as the GCDFP-15/PIP protein and verified that the intensity of GCDFP-15/PIP was significantly lower in pSS patients when compared to both no-SS sicca subjects and healthy controls (p<0.0001). GCDFP-15/PIP expression also correlated with both the salivary flow rate (r=0.312, p=0.023) and MSG biopsies focus score (r=-0.377, p=0.04). Finally, immunohistochemistry confirmed that GCDFP-15/PIP staining was faint in mucus acini and Real Time PCR showed that GCDFP-15/PIP mRNA was significantly lower in pSS patients when compared to both no-SS sicca subjects and healthy controls (p=0.023) thus supporting the hypothesis that the observed reduction of GCDFP-15/PIP in pSS saliva may be related to a decrease in the protein production. CONCLUSION:In this study by different complementary-omic techniques we confirmed the potential role of GCDFP-15/PIP as a novel biomarker for pSS. This finding might also be functionally important as GCDFP-15/PIP has previously been shown to bind to Aquaporin 5 (AQP5), a salivary gland water channel, critical to saliva formation that is known to be downregulated in pSS. It is likely that exploring the GCDFP-15/PIP/AQP5 axis will help better understand the mechanism of salivary gland dysfunction in pSS.
| S-EPMC3884953 | biostudies-literature
Project description: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.
| S-EPMC4412570 | biostudies-literature
Project description:PurposePancreatic cysts frequently pose clinical dilemmas. On one hand, cysts with high-grade dysplasia offer opportunities for cure, on the other hand, those with low-grade dysplasia are easily over treated. Cyst fluid markers have the potential to improve the evaluation of these cysts. Because telomerase activity is commonly activated in malignant cells, we evaluated the diagnostic performance of cyst fluid telomerase activity measurements for predicting histologic grade.Experimental designTelomerase activity was measured using telomerase repeat amplification with digital-droplet PCR in surgically aspirated cyst fluid samples from 219 patients who underwent pancreatic resection for a cystic lesion (184 discovery, 35 validation) and 36 patients who underwent endoscopic ultrasound fine-needle aspiration. Methodologic and clinical factors associated with telomerase activity were examined.ResultsTelomerase activity was reduced in samples that had undergone prior thawing. Among 119 samples not previously thawed, surgical cyst fluids from cystic neoplasms with high-grade dysplasia ± associated invasive cancer had higher telomerase activity [median (interquartile range), 1,158 (295.9-13,033)] copies/μL of cyst fluid than those without [19.74 (2.58-233.6) copies/μL; P < 0.001)]. Elevated cyst fluid telomerase activity had a diagnostic accuracy for invasive cancer/high-grade dysplasia of 88.1% (discovery), 88.6% (validation), and 88.2% (merged). Among cysts classified preoperatively as having "worrisome features," cyst fluid telomerase activity had high diagnostic performance (sensitivity 73.7%, specificity 90.6%, accuracy, 86.1%). In multivariate analysis, telomerase activity independently predicted the presence of invasive cancer/high-grade dysplasia.ConclusionsCyst fluid telomerase activity can be a useful predictor of the neoplastic grade of pancreatic cysts. Clin Cancer Res; 22(20); 5141-51. ©2016 AACRSee related commentary by Allen et al., p. 4966.
| S-EPMC5065739 | biostudies-literature
Project description:Widespread use of cross-sectional imaging and increasing age of the general population has increased the number of detected pancreatic cystic lesions. However, several pathological entities with a variety in malignant potential have to be discriminated to allow clinical decision making. Discrimination between mucinous pancreatic cystic neoplasms (PCNs) and nonmucinous pancreatic lesions is the primary step in the clinical work-up, as malignant transformation is mostly associated with mucinous PCN. We performed a retrospective analysis of all resected PCN in our tertiary center from 2000 to 2014, to evaluate preoperative diagnostic performance and the results of implementation of the consensus guidelines over time. This was followed by a prospective cohort study of patients with an undefined pancreatic cyst, where the added value of cytopathological mucin evaluation to carcinoembryonic antigen (CEA) in cyst fluid for the discrimination of mucinous PCN and nonmucinous cysts was investigated. Retrospective analysis showed 115 patients operated for a PCN, with a correct preoperative classification in 96.2% of the patients. High-grade dysplasia or invasive carcinoma was observed in only 32.3% of mucinous PCN. In our prospective cohort (n = 71), 57.7% of patients were classified as having a mucinous PCN. CEA ≥ 192 ng/mL had an accuracy of 63.4%, and cytopathological mucin evaluation an accuracy of 73.0%. Combining these 2 tests further improved diagnostic accuracy of a mucinous PCN to 76.8%. CEA level and mucin evaluation were not predictive of the degree of dysplasia. These findings show that adding cytopathology to cyst fluid biochemistry improves discrimination between mucinous PCN and nonmucinous cysts.
| S-EPMC4616542 | biostudies-other
Project description:Purpose: Pancreatic cysts are common and pose diagnostic and management challenges. Pancreatic cyst fluid markers have the potential to aid in the management of cysts with concerning imaging findings. Our aim was to evaluate cyst fluid methylated DNA markers for their accuracy for predicting the histologic grade of neoplastic pancreatic cysts.Experimental Design: Pancreatic cyst fluid samples from 183 patients (29 discovery and 154 validation) aspirated after surgical resection were analyzed for methylated DNA at selected genes (SOX17, BNIP3, FOXE1, PTCHD2, SLIT2, EYA4, and SFRP1) using methylation-specific droplet-digital PCR (dd-QMSP). Methylated DNA levels were evaluated for their accuracy at predicting the grade of dysplasia of the pancreatic cyst.Results: All six markers evaluated in the validation set could accurately distinguish high-risk cystic neoplasms (with high-grade dysplasia and/or associated invasive cancer) from low-risk cysts (lower grades of dysplasia) with accuracies from 79.8% to 83.6%. Methylated SOX17 had the highest overall accuracy as a single marker (sensitivity, 78.4%; specificity, 85.6%; accuracy 83.6%, cutoff; 25 methylated DNA molecules/?L cyst fluid). The best four-gene combination had 84.3% sensitivity, 89.4% specificity, and 88.0% accuracy at distinguishing cysts with high-grade dysplasia and/or invasive cancer from those without. All six markers were independent predictors of having invasive cancer/high-grade dysplasia after adjusting for clinical/imaging factors known to be associated with grade of dysplasia. The combination of methylated SOX17 with cytology better predicted neoplastic grade than cytology alone.Conclusions: A panel of methylated gene markers quantified by dd-QMSP can be used to predict the grade of dysplasia of pancreatic cysts. Clin Cancer Res; 23(14); 3935-44. ©2017 AACR.
| S-EPMC5511555 | biostudies-literature
Project description:GATA-binding protein 3 (GATA3) has been identified as a sensitive marker for breast carcinoma but its sensitivity in primary genital extramammary Paget diseases (EMPDs) has not been well studied.Here we investigated immunohistochemical expression of GATA3 in 72 primary genital EMPDs (35 from female, 37 from male; 45 with intraepithelial disease only, 26 with both intraepithelial disease and invasive adenocarcinoma including 14 also metastasis, 1 with metastatic adenocarcinoma only for study). We also compared GATA3 to gross cystic disease fluid protein 15 (GCDFP15) for their sensitivity.Positive GATA3 staining was seen in all 71 (100%) intraepithelial diseases, 25/26 (96%; female 10/10, male 15/16) invasive adenocarcinomas and 14/15 (93%; female 3/3, male 11/12) metastatic adenocarcinomas, respectively. Positive GCDFP15 staining was seen in 46/71 (65%; female 28/34 or 82%, male 18/37 or 49%) intraepithelial diseases, 20/26 (77%; female 9/10, male 11/16) invasive adenocarcinomas, and 12/15 (80%; female 2/3, male 10/12) metastatic adenocarcinomas, respectively (GATA3 versus GCDFP15: p < 0.01 for both intraepithelial disease and invasive adenocarcinoma, p = 0.28 for metastatic adenocarcinoma). In positive-stained cases, GATA3 stained more tumor cells than GCDFP15 (79% versus 25% for intraepithelial disease, 71% vs 34% for invasive adenocarcinoma, 73% vs 50% for metastatic adenocarcinoma, p < 0.01 for all 3 components).Our findings indicate that GATA3 is a very sensitive marker for primary genital EMPDs and is more sensitive than GCDFP15.
| S-EPMC5504764 | biostudies-other
Project description:RATIONALE AND OBJECTIVES:The purpose of this work is to determine if the speed of sound value of a breast cyst can aid in the clinical management of breast masses. Breast macrocysts are defined as fluid-filled tissue masses >1 cm in diameter and are thought to be aberrations of normal development and involution, often associated with apocrine metaplasia. The benign natural history of breast cysts is well known, and it is important to obtain high specificity in breast imaging to avoid unnecessary biopsies in women who have benign diseases, particularly those with dense breast tissue. Transmission ultrasound is a tomographic imaging modality that generates high-resolution, 3D speed of sound maps that could be used to identify breast tissue types and act as a biomarker to differentiate lesions. We performed this study to investigate the microanatomy of macrocysts observed using transmission ultrasound, as well as assess the relationship of speed of sound to the physical and biochemical parameters of cyst fluids. MATERIALS AND METHODS:Cyst fluid samples were obtained from 37 patients as part of a case-collection study for ultrasound imaging of the breast. The speed of sound of each sample was measured using a quantitative transmission ultrasound scanner in vivo. Electrolytes, protein, cholesterol, viscosity, and specific gravity were also measured (in the aspirated cyst fluid) to assess their relationship to the speed of sound values obtained during breast imaging. RESULTS:We found positive correlations between viscosity and cholesterol (r?=?0.71) and viscosity and total protein?×?cholesterol (r?=?0.78). Additionally, we performed direct cell counts on cyst fluids and confirmed a positive correlation of number of cells with speed of sound (r?=?0.74). The speed of sound of breast macrocysts, as observed using transmission ultrasound, correlated with the cytological features of intracystic cell clumps. CONCLUSION:On the basis of our work with speed as a classifier, we propose a spectrum of breast macrocysts from fluid-filled to highly cellular. Our results suggest high-speed cysts are mature macrocysts with high cell counts and many cellular clumps that correlate with cyst microanatomy as seen by transmission ultrasound. Further studies are needed to confirm our findings and to assess the clinical value of speed of sound measurements in breast imaging using transmission ultrasound.
| S-EPMC6286231 | biostudies-literature
Project description:BACKGROUND: There is little knowledge concerning the content and the mechanisms of filling of arachnoid cysts. The aim of this study was to compare the protein content of arachnoid cysts and cerebrospinal fluid by quantitative proteomics to increase the understanding of arachnoid cysts. METHODS: Arachnoid cyst fluid and cerebrospinal fluid from five patients were analyzed by quantitative proteomics in two separate experiments.In a label-free experiment arachnoid cyst fluid and cerebrospinal fluid samples from individual patients were trypsin digested and analyzed by Orbitrap mass spectrometry in a label-free manner followed by data analysis using the Progenesis software.In the second proteomics experiment, a patient sample pooling strategy was followed by MARS-14 immunodepletion of high abundant proteins, trypsin digestion, iTRAQ labelling, and peptide separation by mix-phase chromatography followed by Orbitrap mass spectrometry analysis. The results from these analyzes were compared to previously published mRNA microarray data obtained from arachnoid membranes. RESULTS: We quantified 348 proteins by the label-free individual patient approach and 1425 proteins in the iTRAQ experiment using a pool from five patients of arachnoid cyst fluid and cerebrospinal fluid. This is by far the largest number of arachnoid cyst fluid proteins ever identified, and the first large-scale quantitative comparison between the protein content of arachnoid cyst fluid and cerebrospinal fluid from the same patients at the same time. Consistently in both experiment, we found 22 proteins with significantly increased abundance in arachnoid cysts compared to cerebrospinal fluid and 24 proteins with significantly decreased abundance. We did not observe any molecular weight gradient over the arachnoid cyst membrane. Of the 46 proteins we identified as differentially abundant in our study, 45 were also detected from the mRNA expression level study. None of them were previously reported as differentially expressed. We did not quantify any of the proteins corresponding to gene products from the ten genes previously reported as differentially abundant between arachnoid cysts and control arachnoid membranes. CONCLUSIONS: From our experiments, the protein content of arachnoid cyst fluid and cerebrospinal fluid appears to be similar. There were, however, proteins that were significantly differentially abundant between arachnoid cyst fluid and cerebrospinal fluid. This could reflect the possibility that these proteins are affected by the filling mechanism of arachnoid cysts or are shed from the membranes into arachnoid cyst fluid. Our results do not support the proposed filling mechanisms of oncotic pressure or valves.
| S-EPMC3641952 | biostudies-literature