Diagnostic Usefulness of MUC1 and MUC4 for Distinguishing between Metastatic Adenocarcinoma Cells and Reactive Mesothelial Cells in Effusion Cell Blocks
Abstract:Objective: The aim of our study was to determine the diagnostic value of MUC1 and MUC4 for distinguishing between metastatic adenocarcinoma cells (MAC) and reactive mesothelial cells (RMC) in effusion fluids. Study Design: A total of 237 cell block specimens from pleural and peritoneal effusions, including 196 malignant effusions with MAC and 41 benign effusions with RMC, were stained with antibodies against MUC1 and MUC4. Membranous staining with or without cytoplasmic staining was considered to be positive. … Show more
“…There was minimal consistency in sensitivity and specificity of CEA, Ber-Ep4, MOC-31, and MUC4 in distinguishing MAC from RMC as observed in various studies reported in the literature [6,8,27,28]. The sensitivity ranges from 70.0 to 100%, while the specificity ranges from 51.2 to 100%.…”
Section: Discussionmentioning
confidence: 89%
“…These included various epithelial markers such as carcinoembryonic antigen (CEA), Ber-Ep4, E-cadherin, MOC-31, and mucins [6,8,19,21,27,28]. However, immunocytochemical staining for these epithelial markers was unable to detect cases with MAC that did not express them.…”
Section: Discussionmentioning
confidence: 99%
“…Cell block sections, 4 μm, were stained immunocytochemically using a Bond-Max automatic immunostainer (Leica Microsystems, Bannockburn, Ill., USA), as previously described [28]. Briefly, all steps were performed by the automated instrument according to the manufacturer's instructions in the following order: deparaffinization, heat-induced epitope retrieval (antigen unmasking), peroxide block, incubation with claudin-3 (1:500 dilution, rabbit polyclonal; Invitrogen, Camarillo, Calif., USA) and claudin-4 (1:250 dilution, clone 3E2C1; Invitrogen) primary antibodies, color development with 3,3′-diaminobenzidine tetrahydrochloride chromogen, hematoxylin counterstaining, and mounting of the slides.…”
Objective: Claudin-3 and claudin-4 have recently been reported as promising targets for the detection and diagnosis of cancer. This study was designed to evaluate the diagnostic value of claudin-3 and claudin-4 immunoreactivity to distinguish metastatic adenocarcinoma cells (MAC) from reactive mesothelial cells (RMC) in effusions. Study Design: Claudin-3 and claudin-4 immunocytochemical staining was performed on 234 cell block specimens, including 194 malignant effusions with MAC and 40 benign effusions with RMC. Any degree of membranous staining was considered positive. Results: Claudin-3 was positive in 190 (97.9%) out of 194 cases with MAC and in 3 (7.5%) out of 40 cases with RMC. Claudin-4 immunoreactivity was seen in all 194 (100%) cases with MAC and in 11 (27.5%) out of 40 cases with RMC. In all claudin-3- or claudin-4-positive RMC samples, the area of positive staining was <25% of the cells. Claudin-3 and claudin-4 efficiently discriminated between MAC and RMC (p < 0.001 for both), and claudin-3 was more specific than claudin-4 in differentiating between MAC and RMC (p < 0.05). Conclusion: These results suggest that claudin-3 and claudin-4 are good candidates to be included as MAC markers in the panel of antibodies to distinguish MAC from RMC in effusion specimens.
“…There was minimal consistency in sensitivity and specificity of CEA, Ber-Ep4, MOC-31, and MUC4 in distinguishing MAC from RMC as observed in various studies reported in the literature [6,8,27,28]. The sensitivity ranges from 70.0 to 100%, while the specificity ranges from 51.2 to 100%.…”
Section: Discussionmentioning
confidence: 89%
“…These included various epithelial markers such as carcinoembryonic antigen (CEA), Ber-Ep4, E-cadherin, MOC-31, and mucins [6,8,19,21,27,28]. However, immunocytochemical staining for these epithelial markers was unable to detect cases with MAC that did not express them.…”
Section: Discussionmentioning
confidence: 99%
“…Cell block sections, 4 μm, were stained immunocytochemically using a Bond-Max automatic immunostainer (Leica Microsystems, Bannockburn, Ill., USA), as previously described [28]. Briefly, all steps were performed by the automated instrument according to the manufacturer's instructions in the following order: deparaffinization, heat-induced epitope retrieval (antigen unmasking), peroxide block, incubation with claudin-3 (1:500 dilution, rabbit polyclonal; Invitrogen, Camarillo, Calif., USA) and claudin-4 (1:250 dilution, clone 3E2C1; Invitrogen) primary antibodies, color development with 3,3′-diaminobenzidine tetrahydrochloride chromogen, hematoxylin counterstaining, and mounting of the slides.…”
Objective: Claudin-3 and claudin-4 have recently been reported as promising targets for the detection and diagnosis of cancer. This study was designed to evaluate the diagnostic value of claudin-3 and claudin-4 immunoreactivity to distinguish metastatic adenocarcinoma cells (MAC) from reactive mesothelial cells (RMC) in effusions. Study Design: Claudin-3 and claudin-4 immunocytochemical staining was performed on 234 cell block specimens, including 194 malignant effusions with MAC and 40 benign effusions with RMC. Any degree of membranous staining was considered positive. Results: Claudin-3 was positive in 190 (97.9%) out of 194 cases with MAC and in 3 (7.5%) out of 40 cases with RMC. Claudin-4 immunoreactivity was seen in all 194 (100%) cases with MAC and in 11 (27.5%) out of 40 cases with RMC. In all claudin-3- or claudin-4-positive RMC samples, the area of positive staining was <25% of the cells. Claudin-3 and claudin-4 efficiently discriminated between MAC and RMC (p < 0.001 for both), and claudin-3 was more specific than claudin-4 in differentiating between MAC and RMC (p < 0.05). Conclusion: These results suggest that claudin-3 and claudin-4 are good candidates to be included as MAC markers in the panel of antibodies to distinguish MAC from RMC in effusion specimens.
“…In addition, Cho et al [25] found that detecting the expression level of MUC1 in ascites can help distinguish between metastatic adenocarcinoma cells and reactive mesothelial cells, with a sensitivity of up to 99% and certain diagnostic value. Similar studies have reported that MUC1 immunoreactivity can be detected in ascites samples from patients with ovarian serous carcinoma and pancreatic cancer [26].…”
BackgroundCircular RNAs are key regulators in human cancers, however, there is a lack of studies on circRNAs’ specific functions in ovarian cancer.MethodsOur study used qRT-PCR to detect the differentially expressed circRNAs between normal ovaries and ovarian cancer tissues. Cell function experiments were performed to verify the role of overexpression and silence of circWHSC1, including MTT assay, cell apoptosis assay, wound healing and Matrigel-coated Transwell assay. In vivo tumorigenesis model was constructed by subcutaneous injection in nude mice. Bioinformatics analysis predicted the possible binding sites of circWHSC1 with miRNAs, and confirmed with dual-luciferase reporter assay and RNA pull-down assay. The exosomes were extracted with ultracentrifugation. HE staining was also used to detect morphology of nude mice peritoneum.ResultsWe found that circWHSC1 was up-regulated in ovarian cancer tissues, and circWHSC1 expression was higher in moderate & poor differentiation ovarian cancer tissues than in well differentiation ovarian cancer tissues. Overexpression of circWHSC1 increased cell proliferation, migration and invasion, and inhibited cell apoptosis. Silence of circWHSC1 exerted the opposite effects. Additionally, circWHSC1 could sponge miR-145 and miR-1182 and up-regulate the expression of downstream targets MUC1 and hTERT. Exosomal circWHSC1 can be transferred to peritoneal mesothelial cells and promotes peritoneal dissemination.ConclusionsOur study demonstrates the highly expressed circWHSC1 in ovarian cancer promotes tumorigenesis by sponging miR-145 and miR-1182, and its exosome forms induce tumor metastasis through acting on peritoneal mesothelium.
“…Tumor cells usually lose their original arrangement patterns in cell block sections, and most may bear some overlapping features; for example, the morphology of adenocarcinoma and mesothelioma is quite similar [11,12,13]. Therefore, dependable IHC and molecular pathology results are of great value [14,15].…”
Objective: The technique of conventional cell blocks is rather labor- and time-consuming. The purpose of this study was to generate a convenient and quick manual procedure using ultrasound processing which could be applied in most developing countries and to evaluate its efficacy in the cytopathologic diagnosis of cavity fluids. Study Design: We carried out a rapid cell block procedure using egg albumen as the pre-embedded adjuvant and using ultrasound to accelerate fixation, dehydration, clearing and waxing. The diagnostic efficacy was evaluated as compared with tissue blocks and liquid-based cytology tests (LCTs). Results: A total of 155 samples underwent rapid cell block detection, and 61 were diagnosed as malignancies. The method was able to produce high-quality formalin-fixed paraffin-embedded cell block sections and has similar diagnostic validity to the LCT. The immunohistochemistry and in situ hybridization staining patterns in rapid cell block sections were similar to those in their tissue block counterparts. Conclusions: The ultrasound-processed rapid cell block is a convenient and quick method for cytopathologic diagnosis. We consider it may serve as an effective adjuvant technique for most primary medical institutions.
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