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Background: Neoadjuvant therapy leads to a clinical complete response in a considerable proportion of patients with locally advanced rectal cancer, allowing for possible nonoperative management. The presence of mucin on magnetic resonance imaging (MRI) after neoadjuvant therapy leads to uncertainty about residual disease and appropriateness of a watch-and-wait strategy in patients with no evidence of disease on proctoscopy (endoscopic clinical complete response)., Methods: MRI reports for locally advanced rectal cancer patients seen between July 2016 and January 2020 at Memorial Sloan Kettering Cancer Center were queried for presence of mucin in the tumor bed on MRI following neoadjuvant therapy. Clinicodemographic, pathologic, and outcome data were compiled and analyzed., Results: Of 71 patients with mucin on posttreatment MRI, 20 had a clinical complete response, and 51 had abnormalities on endoscopy and/or physical exam. One patient with a clinical complete response opted out of watch-and-wait; thus, 19 (27%) patients entered watch-and-wait, and 52 (73%) patients were planned for surgery (non-watch-and-wait). Of the 19 watch-and-wait patients, 15 (79%) have had no local regrowth with median follow-up of 50 months (range = 29-76 months), while 4 (21%) experienced regrowth between 9 and 29 months after neoadjuvant therapy. Of the 52 patients who were planned to have surgery (non-watch-and-wait), 49 underwent resection while 3 developed metastatic disease that precluded curative-intent surgery. Of the 49 patients who underwent surgery, 5 (10%) had a pathologic complete response (including the patient with an endoscopic clinical complete response)., Conclusions: The presence of mucin after neoadjuvant therapy for locally advanced rectal cancer does not preclude watch-and-wait management in otherwise appropriate candidates who achieve an endoscopic clinical complete response., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Minor acidic glycans, such as sulfated and phosphorylated glycans, constitute only a small fraction of biological glycome, making their analysis a considerable challenge. In this study, we developed a technique to analyze minor acidic O -glycans in biological samples. First, efficient reaction conditions for the release of O -glycans from the proteins were determined. Next, a high-throughput method was established for the recovery of minor acidic glycans using NH 2 spin columns. The performance of the established method was evaluated using mucin samples, and sulfated O -glycans were successfully detected in bovine submaxillary gland mucin and porcine stomach mucin. We also analyzed the minor acidic O -glycans in cultured cancer cells. In addition to trifucosylated sulfated O -glycans and disulfated O -glycans, sulfated O -glycans with KDN were detected in LS174T cells. The relative amount of sulfated glycans in LS174T cells was almost 10-fold higher than that in the other cells. Moreover, a large polylactosamine-type sulfated O -glycan with a molecular weight >3500 was detected in MKN45 cells. Interestingly, phosphorylated ribose, possibly bound to serine/threonine, was observed in all the cells used in this study. Thus, our established analytical method allows for the analysis of minor acidic O -glycans that cannot be detected using existing glycomics methods.

Mucin-domain glycoproteins are characterized by their high density of glycosylated serine and threonine residues, which complicates their analysis by mass spectrometry. The dense glycosylation renders the protein backbone inaccessible to workhorse proteases like trypsin, the vast heterogeneity of glycosylation often results in ion suppression from unmodified peptides, and search algorithms struggle to confidently analyze and site-localize O-glycosites. We have made a number of advances to address these challenges, rendering mucinomics possible for the first time. Here, we summarize these contributions and provide a detailed protocol for mass spectrometric analysis of mucin-domain glycoproteins. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Enrichment of mucin-domain glycoproteins Basic Protocol 2: Enzymatic digestion of mucin-domain glycoprotein(s) Basic Protocol 3: Mass spectrometry data collection for O-glycopeptides Basic Protocol 4: Mass spectrometry data analysis of O-glycopeptides., (© 2024 Wiley Periodicals LLC.)

Background and Objectives : Mucin has been implicated via various mechanisms in the development and growth of tumour cells. However, mucin expression studies in salivary gland tumours are limited, especially with samples from minor salivary glands. This study aims to investigate and compare mucin expression in benign and malignant salivary gland tumours of minor and major salivary gland origins. Materials and Methods : Special stains were used to stain neutral mucin (Periodic acid Schiff), sialomucin (Alcian Blue) and sulfomucin (Aldehyde Fuschin) within tissues from six normal salivary glands and 73 salivary gland tumours including 31 pleomorphic adenomas, 27 mucoepidermoid carcinomas, and 15 adenoid cystic carcinomas. A semi-quantitative approach was used to evaluate mucin expression within ductal lumens. Sialomucin was the most expressed mucin in all salivary gland tumours, regardless of origin. Results : A significant difference was observed in the mucin expression between benign and malignant salivary gland tumours, as pleomorphic adenoma showed three times significantly higher expression of sialomucin compared to mucoepidermoid carcinoma and adenoid cystic carcinoma ( p = 0.028). Pleomorphic adenomas of major glands showed 42 times significantly higher expression of sialomucin compared to those of minor glands ( p = 0.000). Conclusions : Sialomucin content in pleomorphic adenomas of major glands was vastly increased compared to that in minor glands. Differential sialomucin expression in benign and malignant salivary gland tumours suggests a role in diagnosing of borderline salivary gland tumours., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper.

Introduction : Signet-ring cells are typically associated with mucin-secreting epithelium; thus, they are most commonly found in the gastrointestinal tract, but not exclusively. Primary signet-ring cell carcinoma of the prostate is a rare and poorly differentiated, aggressive acinar adenocarcinoma variant with a grim prognosis. Clinical Case : In June of 2023, a 54-year-old Caucasian male presented with a complaint of lower urinary tract obstructive symptoms with occasional macrohematuria, non-specific body aches, and shortness of breath. A prostate specimen obtained in transurethral resection of the prostate was sent for histopathological examination. After a series of extraprostatic diagnostic workups, including fibrogastroduodenoscopy, colonoscopy computed tomography imaging, and immunohistochemical studies, the patient was diagnosed with primary prostatic signet-ring cell adenocarcinoma stage IV. Unfortunately, due to the advanced stage of the disease, PE, and third-degree thrombocytopenia, the patient was not a candidate for chemotherapy and died of cardiopulmonary insufficiency later that week. Discussion : Prostatic signet-ring cell carcinoma accounts for 0.02% of all prostate adenocarcinoma cases. Due to its nature and epidemiology, a diligent extraprostatic investigation has to be carried out. The disease often presents with unremarkable clinical symptoms and variable serum prostate-specific antigen results, which may contribute to its late diagnosis. Inconsistent immunohistochemical findings and an unpredictable response to hormonal treatment together pose both diagnostic and therapeutic challenges that negatively affect the prognosis. Conclusions : This study highlights the importance of a multidisciplinary approach and the need for diagnostic and therapeutic consensus within the research community in search of the primary site of the disease, which may positively influence the prognosis.

Mucins are often stained with the basic dye Alcian blue, but mucins with a low acidic glycan content cannot be stained with it. Succinylation-Alcian blue staining is a method that temporarily modifies glycans with succinic acid to visualize mucins with low acidic glycan content. This method can be used to stain mucins on polyvinylidene difluoride (PVDF) membranes separated via supported molecular matrix electrophoresis (SMME) and mucins blotted onto PVDF membranes from gel electrophoreses. The succinyl groups of the modified glycans can be easily and completely removed by releasing O-glycan from the stained mucin bands. Therefore, the glycans can be analyzed using the same methods as those used for mucins with a high acidic glycan content., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

For patients with locally advanced rectal cancer (LARC), a pathological complete response (pCR) after pre-operative chemoradiotherapy (CRT) does not necessarily indicate a cure. Acellular mucin pools are often seen in patients with pCR. However, the clinical significance of acellular mucin pools in this group of patients remains unknown. This was a retrospective analysis of 225 LARC patients who achieved pCR following CRT and total mesorectal resection from 2011 to 2018. The outcomes of 5-year disease-free survival (DFS), 5-year overall survival (OS) and 5-year distant metastasis-free survival (DMFS) were compared in patients with versus without acellular mucin pools. Among 225 pCR patients, acellular mucin pools could be identified in 56 (24.9%) patients, and recurrence occurred in 30 (13.3%) patients at 5 years. Distant recurrence was seen in 13 (23.2%) patients with acellular mucin pools and in 17 (10.1%) patients without acellular mucin pools. Patients with acellular mucin pools versus those without had poorer DFS (76.8 versus 89.9%, P = 0.010) and OS (87.5 versus 97.0%, P = 0.004) at 5 years. The presence of acellular mucin pools was the independent parameter that remained significant for DFS [hazard ratio (HR) = 3.904; 95% confidence interval (CI) = 1.342-11.356; P = 0.047] and OS (HR = 3.850; 95% CI = 1.214-12.213; P = 0.022) on multivariate analysis. A total of 17 patients demonstrated acellular mucin pools in primary tumour and lymph nodes. Subgroup analysis demonstrated that pCR patients with acellular mucin pools in primary tumour and lymph nodes were more likely to develop distant metastasis compared to pCR patients with acellular mucin pools only in primary tumour (47.1 versus 12.8%, P = 0.005). In summary, acellular mucin pools in LARC patients with pCR after CRT might represent a sign of invasive tumour biology and significantly shorten the prognosis of patients, especially in patients with acellular mucin pools in lymph nodes., (© 2022 John Wiley & Sons Ltd.)

Jellyfish (JF) mucin (precisely, a mucin-type glycoprotein named qniumucin: Q-mucin) first discovered in JF is mainly composed of highly O-glycosylated domains, and its unique structure suggests its wide applications as a smart material. In this study, the standard protocol used to date was thoroughly reinvestigated because the processing of raw JF was rather difficult and continuous production from frozen sources was also indispensable. Finally, we concluded that Q-mucin is involved not in mucus but in the mesoglea, i.e., the extracellular matrix (ECM), as a part of a very large polymer complex. We added a treatment procedure with a chelate reagent (e.g. EDTA) to inactivate endogenous proteases that induce the spontaneous decomposition of the collagens in ECM. The amino acid composition (AAC) of each precipitate formed upon EtOH addition indicated that Q-mucin dissociates from the biopolymer complex as a constituent highly soluble in deionized water. Since the remaining portion of ECM still seemed to contain a large amount of the precursor of Q-mucin even after the extraction with water is completed, the yield of Q-mucin is expected to increase markedly if an innovative method to decompose EtOH precipitates is developed. The existence of Q-mucin in ECM seems to be described in parallel with that of proteoglycans (PG) in mammalian cartilage because they resemble each other., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The objective of this study was to determine whether differences in the abundance of mucins 5b and 7 as well as secretory IgA exist in the oral acquired pellicle between children with active caries and caries-free children., Design: Pellicle formation was performed for 10 min in-situ on ceramic slabs in the oral cavity of children (5-7 years of age) with caries (n = 15) and without signs of caries (n = 13). Furthermore, unstimulated saliva was collected. Concentrations of Muc5b, Muc7 and sIgA were measured in desorbed pellicle eluates and in saliva., Results: Significantly larger concentrations of Muc5b, Muc7 and sIgA were detected in the pellicle obtained from children with caries compared to caries-free children. However, in the salivary samples concentrations of mucins Muc5b and Muc7 as well as sIgA did not differ significantly between the two groups., Conclusions: All three pellicle components Muc5b, Muc7 as well as sIgA could be identified as potential biomarkers for early childhood caries with high sensitivity and specificity. This could contribute to a better understanding of the different caries susceptibility in children., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: This study aims to investigate the clinical significance and prognostic value of mucinous component (MC) in colorectal adenocarcinoma (AC)., Methods: Patients with colorectal AC and AC with MC (ACMC) (1-100%) underwent surgical resection between January 2007 and February 2018 were retrospectively reviewed. Propensity score matching (PSM) was performed according to a 1:1 ratio. Receiver-operating characteristic (ROC) curve was used to identify the optimal cut-off value of MC ratio for prognostic prediction. The clinicopathological features and 3-year overall survival (OS) of AC patients, mucinous adenocarcinoma (MAC) (MC > 50%) patients, and ACMC (1-50%) patients were compared before and after matching. Multivariable analysis was used for analyzing independent risk factors related to prognosis., Results: A total of 532 patients were enrolled in this study. Patients with AC, MAC, and ACMC (1-50%) exhibited different clinicopathological features. However, their 3-year OS rates were similar (82.00% vs. 74.11% vs. 81.48%, P = 0.38). After matching, ROC curve determined 70% as the optimal cut-off value. And patients with ACMC > 70% had a much poorer 3-year OS compared with ACMC (1-70%) patients and AC patients (47.37% vs. 86.15% vs. 79.76%, P < 0.001). In addition, ACMC > 70% was revealed as a risk factor for poor survival in univariate analysis (HR = 1.643, 95%CI = 1.025-2.635, P = 0.039), though not an independent risk factor in multivariable analysis (HR = 1.550, 95%CI = 0.958-2.507, P = 0.074)., Conclusions: MAC is usually diagnosed at an advanced stage. MAC has a similar survival with AC and ACMC (1-50%) patients before and after matching. Patients with ACMC > 70% exhibited a much poorer OS, and should be given more clinical attention., (© 2021. The Author(s).)

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumour in both adults and children. Histological grading of MEC is subjective, but plays an important role in predicting patient prognosis. Epithelial mucin (MUC) status may aid in establishing a more accurate grade. This study aimed to investigate the expression of various mucins (MUC1, MUC2, MUC4 and MUC5AC) in MECs to determine a possible correlation with tumour grade. Fifteen cases of each tumour grade (low-, intermediate-, and high-grade) were retrieved from the pathology archives of the Department of Oral Pathology and Oral Biology at the University of Pretoria. The patients included 23 men and 22 women, and ranged from 13 to 85 years (mean 49.8 years). Sections from formalin-fixed paraffin-embedded (FFPE) tissue were used for fluorescence in situ hybridization (FISH) for MAML2 rearrangements and MUC immunohistochemical analysis. The percentage immunohistochemical expression of the neoplastic mucous cells was evaluated first, followed by the overall percentage expression of all tumour cells. The results indicated that MUC1 overexpression may be a reliable marker of high-grade MECs, whereas MUC4 overexpression may be more indicative of low-grade tumours. MUC5AC expression was considered an unreliable marker in determining grade. MUC2 was only expressed in a single case of MEC and may be considered a useful marker to exclude MEC as a diagnostic possibility. This study demonstrates that MECs show an altered MUC expression pattern that can be used for diagnostic purposes and to aid in establishing a more accurate tumour grade.

Mucins, the major components of salivary mucus, are large glycoproteins abundantly modified with O-glycans. Mucins present on the surface of oral tissues contribute greatly to the maintenance of oral hygiene by selectively adhering to the surfaces of microbes via mucin O-glycans. However, due to the complex physicochemical properties of mucins, there have been relatively few detailed analyses of the mechanisms controlling the expression of mucin genes and the glycosyltransferase genes involved in glycosylation. Analysis performed using supported molecular matrix electrophoresis, a methodology developed for mucin analysis, and knockout mice without the polycomb group protein Bmi-1 revealed that Bmi-1 regulates mucin levels in the submandibular gland by suppressing the expression of the mucin Smgc gene, and that Bmi-1 also regulates mucin O-glycosylation via suppression of the glycosyltransferase Gcnt3 gene in the submandibular gland., Competing Interests: The authors have declared that no competing interests exist.

Densely O-glycosylated mucin domains are found in a broad range of cell surface and secreted proteins, where they play key physiological roles. In addition, alterations in mucin expression and glycosylation are common in a variety of human diseases, such as cancer, cystic fibrosis, and inflammatory bowel diseases. These correlations have been challenging to uncover and establish because tools that specifically probe mucin domains are lacking. Here, we present a panel of bacterial proteases that cleave mucin domains via distinct peptide- and glycan-based motifs, generating a diverse enzymatic toolkit for mucin-selective proteolysis. By mutating catalytic residues of two such enzymes, we engineered mucin-selective binding agents with retained glycoform preferences. StcE E447D is a pan-mucin stain derived from enterohemorrhagic Escherichia coli that is tolerant to a wide range of glycoforms. BT4244 E575A derived from Bacteroides thetaiotaomicron is selective for truncated, asialylated core 1 structures commonly associated with malignant and premalignant tissues. We demonstrated that these catalytically inactive point mutants enable robust detection and visualization of mucin-domain glycoproteins by flow cytometry, Western blot, and immunohistochemistry. Application of our enzymatic toolkit to ascites fluid and tissue slices from patients with ovarian cancer facilitated characterization of patients based on differences in mucin cleavage and expression patterns., Competing Interests: Competing interest statement: D.J.S., S.A.M., K.P., and C.R.B. are coinventors on a Stanford patent application related to this work. C.R.B. is a cofounder and Scientific Advisory Board member of Lycia Therapeutics, Palleon Pharmaceuticals, Enable Bioscience, Redwood Biosciences (a subsidiary of Catalent), and InterVenn Biosciences, and a member of the Board of Directors of Eli Lilly & Company. O.D. has participated in advisory boards for Tesaro, Merck, and Geneos. O.D. is a speaker for Tesaro and AstraZeneca.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.

Mucins as highly glycosylated proteins comprise multiple functions like protection, homeostasis, immune defense, cell signaling. Various epithelial tissues including glandular structures express different specific mucin types. We investigated labial salivary glands in infants for the occurrence of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC7 by immunohistochemistry. MUC1 and MUC4 were detected in serous and ductal glandular cells, partially intensified at the apical plasma membrane. MUC3 was found in ductal glandular cells and in myoepithelial cells. MUC5B exhibited a mosaic expression pattern in mucous glandular endpieces. MUC2 and MUC7 were abundant in serous acini. Glandular structures were negative for MUC5AC. A comprehensive study of specific mucins in labial salivary glands of infants was presented for the first time. As a representative of the minor salivary glands, labial glands are, due to their localization, directly exposed to environmental influences. The distribution of a broad spectrum of mucins in infantile labial glands indicates their importance early in human development to sustain oral health.

: To evaluate the cervical-vaginal mucin, CA125, as a measure of fertility and possible method for natural family planning (NFP). Cervical-vaginal fluid (CVF) swab samples have been previously used to measure CA125, 'Qvaginal CA125 levels', as a function of time of cycle relative to Day 0, the first day of positive urine LH (luteinizing hormone). Data from 15 women, 20 cycles were used with an algorithm to establish the Fertile Start Day (FSD) for the cycles. The FSD was determined as either the second consecutive day of ≥20% Qvaginal CA125 rise or the first day of ≥400% rise. The interval, (FSD to Day +3), was used as the theoretical window of fertility, and conception rates assuming abstinence during this predicted period of fertility were computed using published day-specific probabilities of conception ( PoC ). The mean FSD was Day -4.8 ± 0.5 (SE), 95% CI (-5.9, -3.7). The estimated pregnancy failure rate (PFR) with abstinence during [FSD, +3] was 10.7% ± 2.0% (SE), 95% CI (6.9%, 14.8%); with exclusion of one cycle with very low levels of Qvaginal CA125, the estimated PFR was 9.8% ± 1.9%, 95% CI (6.3%, 13.8%). Furthermore, the day-specific Qvaginal CA125 values were normalized to the respective peak Qvaginal CA125 for each cycle, and a mean normalized day-specific Qvaginal CA125 plot was generated. The first derivative of the mean normalized day-specific Qvaginal CA125 plot showed a significant increase between Day -4.5 and Day -3.5, which correlated with the mean FSD. A Qvaginal CA125-based method holds promise as a means to identify the start of the fertile window and may prove useful in NFP, especially when combined with available home hormonal fertility awareness kits., Competing Interests: The authors declare no conflict of interest.

Vitreo-retinal (VR) surgeries induce conjunctival changes. However, there are no study reports regarding prevalence and severity of dry eye after these surgeries. This study evaluated dry eye outcome after VR surgery. Patients undergoing VR surgery classified as scleral buckle and microincision vitrectomy surgery (n = 44, mean age: 56.09±10.2 years) were recruited. Dry eye evaluation was done before and 8 weeks after surgery (2 weeks after omitting topical eye drops). Conjunctival imprint cytology for goblet cell count and tear Mucin 5AC (MUC5AC) protein estimation was done. Gene expressions of MUC5AC, MUC4, MUC16, Aquaporin 4 (AQP4) and AQP5 were analyzed in the conjunctival imprint cells by qPCR. None of the patients exhibited clinical signs of dry eye after VR surgery. But the conjunctival goblet cell density (GCD) was significantly lowered post-VR surgery (63% cases, **p = 0.012) with no alterations in the tear MUC5AC protein. Post-VR surgery, the conjunctival cell gene expression of MUC4, MUC16 and AQP4 were significantly increased (*p = 0.025, *p = 0.05 and *p = 0.02 respectively) and AQP5 was significantly lowered (*p = 0.037), with no change in MUC5AC expression. Tear cytokines were significantly increased post-VR surgery (anti-inflammatory: IL1RA, IL4, IL5, IL9, FGF; PDGFbb and pro-inflammatory: IL2, IL6, IL15, GMCSF and IFNg). Though clinical signs of dry eye were not observed after VR surgery, ocular surface changes in the form of reduced GCD, altered MUC5AC, MUC4, MUC16, AQP4, AQP5 and cytokines are suggestive of dry eye outcome at the molecular level especially inpatients aged above 51 years, especially female gender and those who are diabetic., Competing Interests: The authors have read the journal’s policy and have the following conflicts: Novartis Healthcare Private Limited funded this project. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Purpose: To determine the prognostic value of diffusion-weighted magnetic resonance imaging (DW-MRI) of mucin pools (MPs) in predicting the response of patients with locally advanced rectal mucinous adenocarcinoma (RMAC) to neoadjuvant therapy (NAT)., Method: A total of 59 patients with histologically proven RMAC received NAT before applying total mesorectal excision. MP and solid tumor (ST) components were identified using T2 weighted image (T2WI) and DW-MRI, and apparent diffusion coefficient (ADC) values were calculated prior, during and after NAT. The receiver operating characteristic (ROC) curve was used to evaluate the ability of ADC values in predicting NAT efficacy as determined by post-pathological tumor regression grade (TRG). In addition, radiologists evaluated the TNM staging of tumors, the mesorectal fascia invasion, the maximal tumor length, and the distance from the inferior part of the tumor to the anal verge. Multivariate analysis and logistic regression were used to determine the correlation of ADC values and baseline MRI parameters with NAT efficacy., Results: Among the 59 patients, 44 (74.6 %) were men. The mean age of patients was 49.5 ± 11.2 years. The mean ΔADC value during NAT obtained on mucus pool was higher in the responsiveness group than that of the nonresponsiveness group (0.506 ± 0.342 vs. 0.053 ± 0.240 × 10 -3 mm 2 /s, P < .001), with an area under the curve of receiver operating characteristic of 0.881 (95 %CI, 0.770-0.951)., Conclusions: MRI can be reliably used to measure MP-ADC, which as we showed in this study, represents a biomarker to predict tumor responsiveness of NAT in RMAC patients., Competing Interests: Declaration of Competing Interest The authors declare no existing conflicts of interest, financial, professional, or otherwise., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Mucin-type glycoproteins are the principal components of mucus which cover all the mucosal surfaces of the human body. The mucus and mucins are essential mediators of the innate immune system, however in the last decades mucins have been identified even as an important class of cancer biomarkers. Luminogenic materials with fluorescence turn-on behavior are becoming promising materials because of their advantages of label free, relatively inexpensive and simple to use properties for biological detection and imaging. Squaraines are luminogens characterized by high fluorescence in organic media but poor emission in aqueous environments due to their tendency to self-aggregate. Herein we investigate the interaction between porcine gastric mucin (PGM) and several squaraines in aqueous media. While squaraine dyes showed low fluorescence intensity and quantum yield in water, as a result of the formation of aggregates, an enhancement of fluorescence up to 45-fold was achieved when PGM was added. PGM was detected in a linear range of 10-300 μg/mL with a limit of detection of 800 ng/mL. The assay was used to quantify mucin in diluted human serum samples and recoveries of 94.9-116.2% were achieved. To the best of our knowledge, this is the easiest and convenient method for mucin detection in the reported literature., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: The cell block technique for assessing endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) specimens from pancreatic mucinous cystic lesions (MCLs) was systematically evaluated for the first time, including comparisons with three traditional methods of assessing such specimens., Methods: The prospective arm comprised EUS-FNA specimens from EUS-suspected pancreatic MCLs. The retrospective arm comprised EUS-FNA specimens from pancreatic MCLs surgically resected before the study start. For each specimen, these data points were collected: macroscopic likelihood of mucin, cyst fluid carcinoembryonic antigen (CEA) level and presence of mucin in air-dried, direct smears and in cell block preparations., Results: The prospective and retrospective arms of the study comprised 80 and 30 EUS-FNA specimens, respectively. Seven prospective cases led to surgical resections during the study, and therefore, 37 EUS-FNA specimens were confirmed to have originated from MCLs. In the prospective arm, macroscopic mucin was suspected, cyst fluid CEA level exceeded 192 ng/mL, mucin was detected in direct smears and cell block preparations in 78%, 30%, 39% and 73% of cases, respectively. Of the 37 specimens confirmed to originate from MCLs, macroscopic mucin assessment, cyst fluid CEA level, direct smear mucin assessment and cell block mucin assessment had sensitivities for diagnosing MCL of 87%, 45%, 45% and 81%, respectively., Conclusions: Cell block preparations are as likely to identify mucin from pancreatic MCLs as macroscopic assessment but are twice as likely to diagnose MCL than direct smears and fluid CEA biochemistry. The cell block technique is easy for sample collection and processing especially because these are identical for solid and cystic pancreatic lesions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Mucus secretion and mucociliary transport are essential defense mechanisms of the airways. Deviations in mucus composition and secretion can impede mucociliary transport and elicit airway obstruction. As such, mucus abnormalities are hallmark features of many respiratory diseases, including asthma, cystic fibrosis and chronic obstructive pulmonary disease (COPD). Studying mucus composition and its physical properties has therefore been of significant interest both clinically and scientifically. Yet, measuring mucus production, output, composition and transport presents several challenges. Here we summarize and discuss the advantages and limitations of several techniques from five broadly characterized strategies used to measure mucus secretion, composition and mucociliary transport, with an emphasis on the gel-forming mucins. Further, we summarize advances in the field, as well as suggest potential areas of improvement moving forward.

Objective: To study the clinicopathological features of invasive lobular carcinoma (ILC) of the breast with extracellular mucin and outcomes of patients. Method: Clinicopathological features and clinical follow-up (39-123 months and a median follow-up of 55 months) of seven ILC with extracellular mucin were obtained. Hematoxylin-and-eosin (H&E) and immunohistochemistry (IHC) stained sections were reviewed, and fluorescence in situ hybridization (FISH) assay was performed for tumors with HER2 IHC 2+. Patient prognosis was analyzed and literatures related to ILC with extracellular mucin were reviewed. Results: All seven patients were female, aged from 43 to 73 years (median age, 55 years). The tumors ranged in size from 1 to 5 cm (median size 2 cm). All seven cases were of histological grade 2. Most areas of the tumors presented with the morphology of classic ILC, and variable amount of extracellular mucin were observed focally. In six cases, part of the tumor cells contained intracellular mucin, and the nucleus were pushed to one side of the cells, creating the impression of signet-ring cells. Two patients had lymph node metastases at diagnosis, and developed liver and bone metastases at 38th and 48th month, respectively, after surgery, and died at 48th and 123th month, respectively. While the other five patients, except one lost to follow-up, had been disease-free during the follow-up period. IHC results showed estrogen receptor (ER) and progesterone receptor (PR) positivity in 7/7 and 6/7 cases, respectively. Tumors of six patients were HER2 IHC 0/1+. The remaining one was HER2 IHC 2+, while FISH assay revealed HER2 gene amplification in that tumor. The proportion of cases with HER2-positivity was 1/7. The proliferation index Ki-67 ranged from less than 5% to 30%, and Ki-67 less than or equal to 10% were in 5/7 cases. According to the 2013 St. Gallen International Expert Consensus on breast cancer, all tumors were of luminal types; of those, two were luminal A and five were luminal B. Conclusions: ILC with extracellular mucin tends to occur in women over 50 years old. All tumors in the study are grade 2 classic ILC, with signet-ring cells as a common feature. All seven tumors are classified as luminal types, with luminal B as the main molecular subtype.

Mucins are a key component of the surface mucus overlying airway epithelium. Given the different functions of the olfactory and respiratory epithelia, we hypothesized that mucins would be differentially expressed between these 2 areas. Secondarily, we evaluated for potential changes in mucin expression with radiation exposure, given the clinical observations of nasal dryness, altered mucus rheology, and smell loss in radiated patients. Immunofluorescence staining was performed to evaluate expression of mucins 1, 2, 5AC, and 5B in nasal respiratory and olfactory epithelia of control mice and 1 week after exposure to 8 Gy of radiation. Mucins 1, 5AC, and 5B exhibited differential expression patterns between olfactory and respiratory epithelium (RE) while mucin 2 showed no difference. In the olfactory epithelium (OE), mucin 1 was located in a lattice-like pattern around gaps corresponding to dendritic knobs of olfactory sensory neurons, whereas in RE it was intermittently expressed by surface goblet cells. Mucin 5AC was expressed by subepithelial glands in both epithelial types but to a higher degree in the OE. Mucin 5B was expressed by submucosal glands in OE and by surface epithelial cells in RE. At 1-week after exposure to single-dose 8 Gy of radiation, no qualitative effects were seen on mucin expression. Our findings demonstrate that murine OE and RE express mucins differently, and characteristic patterns of mucins 1, 5AC, and 5B can be used to define the underlying epithelium. Radiation (8 Gy) does not appear to affect mucin expression at 1 week., Level of Evidence: N/A (Basic Science Research).IACUC-approved study [Protocol 200065]., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Mucins are of great interest in intestinal research and histochemical methods are often employed to identify them. Since it is in the nature of mucins that they are "hard to hold onto" once they come into contact with water, a frequently used medium in histochemistry, there are a number of challenges that may decrease diagnostic accuracy. As the outcome of methods published for microscopic detection of mucosubstances proved to be unsatisfactory in our hands, the aim was the establishment of a reliable and reproducible protocol. Tissue samples were available from pig feeding experiments. In the present study, we focus on a fixation / staining procedure without making comparisons between differently fed pigs. Several fixation and staining procedures were evaluated for their use in semiautomatic quantification and quality assessment of different mucus fractions simultaneous on one tissue section. Cryostat sectioning, subsequent fixation steps with heat, ethanol and modified Bouin's solution, followed by triple staining with high iron diamine, alcian blue and periodic acid-Schiff turned out to be the best method to identify sulfomucin, sialomucin and neutral mucin simultaneous on one tissue section. This methodology resulted in very good morphology of goblet cells with intact mucin containing vesicles within the cells, which was comparable to ultrastructural electron microscopical observations. Semiautomatic quantification of different mucins was possible. In conclusion, reliable mucus quantification and assessment of mucus quality requires strictly tested procedures. According to our experience, the most important aim after cryosectioning is fast fixation of the mucosubstances, which requires a combination of different fixation steps.

Background: Chronic rhinosinusitis (CRS) with eosinophilic mucin is considered rare in Korea. The object of this study was to categorize CRS patients with eosinophilic mucin into several groups and compared the groups based on their clinicopathological and radiological features., Methods: In total, 105 CRS patients with eosinophilic mucin from four tertiary medical centers which are located at Chungcheong province of Korea were included for this study. The patients were divided into four groups for analysis, based on the presence or absence of an allergy (A) to a fungus or fungal element (F) in the mucin. The following were the four groups: allergic fungal rhinosinusitis (AFRS, A+F+), AFRS-like sinusitis (A+F-), eosinophilic fungal rhinosinusitis (EFRS, A-F+), and eosinophilic mucin rhinosinusitis (EMRS, A-F-). Their clinical manifestation, the presence of associated disease, radiological finding, treatment, and treatment outcome were reviewed and compared., Results: There were no patients in the AFRS-like sinusitis group, 47 patients were assigned to the AFRS group, 27 to the EFRS group, and 41 to the EMRS group. Patients of AFRS group showed a significantly higher association with allergic rhinitis than did the other groups. The mean total serum IgE level in the AFRS patients was significantly higher than in the EFRS and EMRS patients. In the AFRS group and EFRS group, 67.6% and 74.1% had unilateral disease, respectively, in contrast to the EMRS group (4.9%). The mean Hounsfield unit values of the area of high attenuation in the AFRS patients were significantly higher than those in the other groups., Conclusions: Significant clinicopathological differences existed among the subgroups of CRS with eosinophilic mucin. AFRS tends to be an allergic response to colonizing fungi in atopic individuals. In EFRS, local allergies to fungi might play a role in the disease. EMRS is thought to be unconnected with fungal allergies, and it showed different form compared with the AFRS and EFRS groups.

Background: Chewing Betel (areca-nut) can cause oral cancer. This happens when its components are in direct contact with the oral epithelium. The aim of this study is to understand this mechanism by analyzing salivary mucins, in vitro, during and after betel chewing., Methods: The in vivo analysis would necessarily involve subtraction of betel to understand its effects. This study analyzed the interaction between mucins and betel in vitro. We added increasing amounts of areca powder, and for comparison an equal amount of pure vine tannin to saliva samples provided by a first volunteer. This study analyzes salivary mucins in two volunteers, one of whom is a regular betel consumer, after chewing the areca-nut, on six saliva samples taken at half-hour intervals., Results: In vitro, total precipitation of the salivary mucins occurs after we added 1g of Areca nut (50 mg Tannin equivalent), a concentration five times lower than what is actually present during the chewing period; in vivo, in the first volunteer, there is a statistically significant increase in the mucins after chewing two and half hours: p-value = 0.02034, while for the regular betel consumer there is a significant decrease: p-value = 0.00512., Discussion: In vitro, we conclude that the polyphenol content in betel causes total precipitation of mucins and causes poor defense of the oral epithelium. The increase of mucins in the non-routine consumers, show a transient (up to two hours after the end of chewing) inflammatory process. Inflammation can cause keratinization of the oral epithelium because the saliva increases its viscosity for the higher amount of mucins, with its lower adherence and protection of the oral cavity. Subsequent and regular consumption of betel nut, as in the regular betel consumer, can cause chronic fibrosis in the oral epithelium and cut the salivary mucins.

Purpose: To evaluate the inflammatory reaction and measure the content of mucins, in the colonic mucosa without fecal stream submit to intervention with mesalazine., Methods: Twenty-four rats were submitted to a left colostomy and a distal mucous fistula and divided into two groups according to euthanasia to be performed two or four weeks. Each group was divided into two subgroups according daily application of enemas containing saline or mesalazine at 1.0 g/kg/day. Colitis was diagnosed by histological analysis and the inflammatory reaction by validated score. Acidic mucins and neutral mucins were determined with the alcian-blue and periodic acid of Schiff techniques, respectively. Sulfomucin and sialomucin were identified by high iron diamine-alcian blue technique. The tissue contents of mucins were quantified by computer-assisted image analysis. Mann-Whitney test was used to analyze the results establishing the level of significance of 5%., Results: Enemas with mesalazine in colonic segments without fecal stream decreased the inflammation score and increased the tissue content of all subtypes of mucins. The increase of tissue content of neutral, acid and sulfomucin was related to the time of intervention., Conclusion: Mesalazine enemas reduce the inflammatory process and preserve the content of mucins in colonic mucosa devoid of fecal stream.

Aims: The process of differential diagnosis between epithelioid mesothelioma and lung adenocarcinoma has been progressing; however, there are no absolute immunohistochemical markers with which to definitively diagnose epithelioid mesothelioma. The aim of this study was to search for a novel negative marker of epithelioid mesothelioma., Methods and Results: We immunohistochemically studied the applicability of mucin 21 (MUC21), which was identified in our previous study, as a novel, negative diagnostic marker for epithelioid mesothelioma. Seventy epithelioid mesotheliomas and 70 lung adenocarcinomas were investigated for the expression of MUC21, along with other previously reported markers, by the use of immunohistochemistry. MUC21 was expressed in only two of the 70 (3%) epithelioid mesotheliomas, as compared with 67 of the 70 (96%) lung adenocarcinomas. The sensitivity, specificity and accuracy of negative MUC21 expression for differentiating epithelioid mesothelioma from lung adenocarcinoma were 97%, 96%, and 96%, respectively; these are similar to those of carcinoembryonic antigen and claudin-4, and better than those of thyroid transcription factor-1, napsin-A, and mucin 4., Conclusion: MUC21 could be used as an additional, novel, negative immunohistochemical marker to differentiate mesothelioma from lung adenocarcinoma., (© 2018 John Wiley & Sons Ltd.)

Background: Intraductal papillary mucinous neoplasms (IPMN) are currently managed based on imaging characteristics and cyst fluid sampling. This study was designed to determine if MUC13, a glycoprotein aberrantly overexpressed in pancreatic adenocarcinoma, might aid in distinguishing high-risk lesions (high grade dysplasia/invasive disease) from low-grade lesions., Methods: MUC13 immunohistochemical staining was performed on surgically resected formalin-fixed tissue specimens from 49 IPMNs and 23 non-mucinous cysts. Membranous MUC13 expression was measured by H-score, which quantifies staining intensity and the percentage of cells involved (range 0-300)., Results: MUC13 expression was detected in all IPMNs and was significantly greater than in non-mucinous cysts (median 210 vs 40, p < 0.001). MUC13 expression was similar among main (n = 26), branch (n = 15), and mixed (n = 8) duct lesions (median 210, 200, 225, respectively). The highest expression was observed in tumors with intestinal and pancreatobiliary histologic features (both median 225) and the lowest in gastric type lesions (median 200). MUC13 expression was significantly greater in high-risk lesions (n = 21) compared to those with low-grade dysplasia (n = 28) (median 250 vs 195, p < 0.001)., Conclusion: MUC13 expression was significantly greater in high-risk IPMNs in this analysis. The preoperative assessment of MUC13 in cyst fluid samples warrants further investigation., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Intraductal papillary mucinous neoplasms (IPMNs) characteristically consist of mucin-filled dilated ducts lined with neoplastic cells forming papillae with a diverse range of morphologies and varying grades of atypia. Based on morphological characteristics and immunohistochemical reaction against mucin proteins, IPMNs are classified into four distinct subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. In this chapter, histomorphological criteria and techniques of immunohistochemical staining and its evaluation for subtyping IPMNs are described.

Background: Mucin 13 (MUC13) is a cell surface glycoprotein aberrantly expressed in a variety of epithelial carcinomas. Thus far, the role of MUC13 in various diseases remains elusive. To the best of our knowledge, this is the first study to examine the potential of MUC13 as a serum biomarker in a variety of carcinomas and other conditions., Methods: We developed a recombinant MUC13 protein, mouse monoclonal antibodies and enzyme immunoassay (ELISA) for MUC13. We used this assay to measure MUC13 levels in the supernatants of cancer cell lines and a large cohort of serum samples from healthy and diseased individuals., Results: MUC13 is secreted from cancer cell lines, with highest levels found in ovarian cancer cell lines. MUC13 levels in human sera were significantly increased in patients with renal failure and 20%-30% of patients with ovarian, liver, lung and other cancers. MUC13 was also elevated in 70% of patients with active cutaneous melanoma, but not uveal melanoma. Furthermore, we identified significant MUC13 elevations in the serum of patients with vasculitis (ANCA-positive) autoantibodies, but not in those with inflammatory bowel disease., Conclusions: Serum MUC13 is frequently elevated not only in a variety of malignant cases but also in some benign pathologies, thus appearing to be a non-specific disease biomarker. Nonetheless, serum MUC13 is clearly highly elevated in some carcinoma patients, and its relationship with tumor progression in this context warrant further research. Future studies that examine the correlation between serum MUC13 levels to stage of cancer could elucidate prognostic potential.

The viscosity variation of sputum is a common symptom of the progression of Chronic Obstructive Pulmonary Disease (COPD). Since the hydration of the sputum defines its viscosity level, dielectric sensors could be used for the characterization of sputum samples collected from patients for early diagnosis of COPD. In this work, a CMOS-based dielectric sensor for the real-time monitoring of sputum viscosity was designed and fabricated. A proper packaging for the ESD-protection and short-circuit prevention of the sensor was developed. The performance evaluation results show that the radio frequency sensor is capable of measuring dielectric constant of biofluids with an accuracy of 4.17%. Integration of this sensor into a portable system will result in a hand-held device capable of measuring viscosity of sputum samples of COPD-patients for diagnostic purposes.

Purpose: To investigate the effects of Helicobacter pylori (H. pylori)-CagA and the urease metabolite NH₄⁺ on mucin expression in AGS cells., Materials and Methods: AGS cells were transfected with CagA and/or treated with different concentrations of NH₄CL. Mucin gene and protein expression was assessed by qPCR and immunofluorescence assays, respectively., Results: CagA significantly upregulated MUC5AC, MUC2, and MUC5B expression in AGS cells, but did not affect E-cadherin and MUC6 expression. MUC5AC, MUC6, and MUC2 expression in AGS cells increased with increasing NH₄⁺ concentrations until reaching a peak level at 15 mM. MUC5B mRNA expression in AGS cells (NH₄⁺ concentration of 15 mM) was significantly higher than that at 0, 5, and 10 mM NH₄⁺. No changes in E-cadherin expression in AGS cells treated with NH₄⁺ were noted, except at 20 mM. The expression of MUC5AC, MUC2, and MUC6 mRNA in CagA-transfected AGS cells at an NH₄⁺ concentration of 15 mM was significantly higher than that at 0 mM, and decreased at higher concentrations. The expression of MUC5B mRNA increased with increases in NH₄⁺ concentration, and was significantly higher compared to that in untreated cells. No significant change in the expression of E-cadherin mRNA in CagA-transfected AGS cells was observed. Immunofluorescence assays confirmed the observed changes., Conclusion: H. pylori may affect the expression of MUC5AC, MUC2, MUC5B, and MUC6 in AGS cells via CagA and/or NH₄⁺, but not E-cadherin., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018.)

Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a primary pancreatic ductal epithelial neoplasm with the potential to develop into an invasive adenocarcinoma. This study aimed to investigate the clinicopathologic and prognostic significance of four potential biomarkers for the preoperative evaluation of patients with IPMN., Materials and Methods: Clinicopathologic materials from 104 patients with IPMN who underwent surgical resection at Jichi Medical University Hospital were analyzed. IPMNs (110 lesions in total) were histologically classified into low-grade IPMN (Group 1; n = 68), high-grade IPMN (Group 2; n = 16), or IPMN with an associated invasive carcinoma (Group 3; n = 26). We evaluated the immunohistochemical expression of MUC13, AGR2, FUT8, and FXYD3, which were previously reported to be overexpressed in pancreatic ductal adenocarcinoma., Results: The expression of MUC13 was more common in Group 3 compared with groups 1 and 2 (p < 0.001) and was associated with poor prognosis (p = 0.004). The expression of MUC13 was not associated with age, sex, tumor location, histological subtype, lymphatic or vascular invasion, or neural invasion. In most cases of IPMN, the loss of expression of AGR2 appeared to show an association with tumor recurrence and poorly differentiated histology of invasive carcinoma; however, this association was not statistically significant. The expressions of FUT8 and FXYD3were not associated with the clinicopathological features of IPMNs., Conclusions: The results suggest that MUC13 overexpression and loss of expression of AGR2 may predict the progression of IPMN and an unfavorable prognosis in patients with IPMN., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

A novel fluorescent molecular probe is reported, which is able to detect glycoproteins, especially mucins, with high sensitivity and with a turn-on response along with a large Stokes shift (>130 nm), within the biologically active window. The probe contains an aminotricarbocyanine as the fluorescent reporter with a linked benzoboroxole as the recognition unit, which operates through a dynamic covalent reaction between the boronic hemiester residue of the receptor and cis-diols of the analyte. The superior selectivity of the probe is displayed by the labeling of mucins present in Calu-3 cells. The new benzoboroxole fluorescent derivative gathers together key properties to make it a highly rated molecular probe: specificity, excellent solubility in water, and off-on near infrared emission. This probe is expected to be an excellent tool for imaging intracellular mucin to evaluate mucus-related diseases as well as a sensing strategy towards glycosylated structures with a high potential for theranostics approaches in biological samples., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The stearoyl-CoA desaturase (SCD) family of enzymes catalyzes monounsaturated fatty acid synthesis by inserting a cis double bond at the Δ9 position of saturated fatty acids. Disruption of these enzymes has been reported to induce a severe dry skin phenotype. Since lipid abnormalities in the meibomian glands have been associated with dry eye, we analyzed selected eye tissues contributing to tear volume and composition in genetically SCD-1-deficient mice (SCD-1 KO), including the lacrimal glands and conjunctiva. Previous histopathological analysis had revealed atrophy and loss of meibomian glands; taken together with the increased goblet cell and MUC5AC expression in the conjunctiva reported here, these findings suggest that the tear volume and mucin levels secreted are enhanced in the absence of lipid secretion as a compensatory mechanism. The expression of lipid metabolism genes in lacrimal glands was decreased in SCD1 KO mice. Thus, these results provide new pathophysiological mechanisms to pursue with regard to meibomian gland dysfunction. In addition, lack of SCD-1 causes a compensatory increase in the tear volume and mucin levels associated with changes in expression of lipid metabolism genes. These results may be useful as a new concept for dry eye treatment strategies.

Purpose: The purpose of this retrospective study was to evaluate imaging features of mucinous nonneoplastic cyst (MNNC) of the pancreas., Materials and Methods: Three (0.9%) patients with MNNC of the pancreas were found in 335 surgically resected pancreatic cystic lesions. Three MDCT and two MRI/MRCP studies were retrospectively reviewed., Results: Three cases of MNNC were found in the pancreatic neck, body, and tail, respectively. All the three cases were multilocular without communication with the main pancreatic duct (MPD), although upstream MPD dilatation was seen in two of the three cases. The signal intensity of the cyst fluid was low on T1-weighted, high on T2-weighted, and low on diffusion-weighted images. Cyst wall was thin in two cases, and the remaining case with obstructive pancreatitis showed visible cyst wall enhancement., Conclusion: Imaging findings of MNNC of the pancreas were nonspecific without communication with the MPD. Cyst wall is typically thin without visible enhancement.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic bronchitic and emphysematous components. In one biophysical model, the concentration of mucin on the airway surfaces is hypothesized to be a key variable that controls mucus transport in healthy persons versus cessation of transport in persons with muco-obstructive lung diseases. Under this model, it is postulated that a high mucin concentration produces the sputum and disease progression that are characteristic of chronic bronchitis., Methods: We characterized the COPD status of 917 participants from the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) using questionnaires administered to participants, chest tomography, spirometry, and examination of induced sputum. Total mucin concentrations in sputum were measured with the use of size-exclusion chromatography and refractometry. In 148 of these participants, the respiratory secreted mucins MUC5AC and MUC5B were quantitated by means of mass spectrometry. Data from chronic-bronchitis questionnaires and data on total mucin concentrations in sputum were also analyzed in an independent 94-participant cohort., Results: Mean (±SE) total mucin concentrations were higher in current or former smokers with severe COPD than in controls who had never smoked (3166±402 vs. 1515±152 μg per milliliter) and were higher in participants with two or more respiratory exacerbations per year than in those with zero exacerbations (4194±878 vs. 2458±113 μg per milliliter). The absolute concentrations of MUC5B and MUC5AC in current or former smokers with severe COPD were approximately 3 times as high and 10 times as high, respectively, as in controls who had never smoked. Receiver-operating-characteristic curve analysis of the association between total mucin concentration and a diagnosis of chronic bronchitis yielded areas under the curve of 0.72 (95% confidence interval [CI], 0.65 to 0.79) for the SPIROMICS cohort and 0.82 (95% CI, 0.73 to 0.92) for the independent cohort., Conclusions: Airway mucin concentrations may quantitate a key component of the chronic bronchitis pathophysiologic cascade that produces sputum and mediates disease severity. Studies designed to explore total mucin concentrations in sputum as a diagnostic biomarker and therapeutic target for chronic bronchitis appear to be warranted. (Funded by the National Heart, Lung, and Blood Institute and others.).

Objective: To investigate the effect of annexin A2 (AnxA2) on epithelial growth factor receptor (EGFR)/nuclear factor-κB (NF-κB) signal transduction and mucin expression in human airway epithelial H292 cells treated with Mycoplasma pneumoniae (MP)., Methods: H292 cells were divided into control group, MP group, NC-siRNA+MP group, and AnxA2 siRNA+MP group. The cells in the MP group were incubated with 5 μg/mL MP antigen for 2 hours. The cells in the NC-siRNA+MP and AnxA2 siRNA+MP groups were transfected with NC-siRNA and AnxA2 siRNA for 24 hours, followed by MP antigen stimulation for 2 hours. The MTT method was used to measure cell viability; quantitative real-time PCR was used to measure the mRNA expression of AnxA2; Western blot was used to measure the protein expression of AnxA2, phosphorylated EGFR (p-EGFR), and phosphorylated p65 NF-κB (p-p65 NF-κB); ELISA was used to measure the secretion of mucin 5AC (MUC5AC) and mucin 5B (MUC5B)., Results: The MP and NC-siRNA+MP groups had lower cell viability than the control group (P<0.05). The AnxA2 siRNA+MP group had higher cell viability than the MP and NC-siRNA+MP groups and lower cell viability than the control group (P<0.05). The MP and NC-siRNA+MP groups had significantly higher mRNA and protein expression of AnxA2 than the AnxA2 siRNA+MP group (P<0.05). Compared with the control group, the MP and NC-siRNA+MP groups had significant increases in the protein expression of p-EGFR, p-p65 NF-κB, MUC5AC, and MUC5B (P<0.05); the AnxA2 siRNA+MP group had lower protein expression than the MP and NC-siRNA+MP groups, but higher protein expression than the control group (P<0.05)., Conclusions: AnxA2 is involved in the airway lesion induced by MP antigen via mediating EGFR/NF-κB signaling activation and mucin expression in human airway epithelial cells.

Purpose: The clinical implications of mucinous components in rectal tumors, especially with regard to the efficacy of neoadjuvant chemoradiotherapy, remain unclear., Methods: One hundred and thirty rectal cancer patients who received curative resection after neoadjuvant chemoradiotherapy were retrospectively reviewed. Patients were classified into 3 groups according to the proportion of extracellular mucin: low (<5 %), moderate (5-25 %), and high (>25 %)., Results: There were 82 (63.1 %), 26 (20.0 %), and 22 (16.9 %) patients in the low, moderate, and high mucin groups, respectively. Patients with a high mucinous tumor component were significantly more likely to have an advanced tumor stage (p = 0.010) and a shorter disease-free (p = 0.002) and distant recurrence-free survivals (p < 0.001), whereas the mucinous tumor component showed no correlation with local recurrence (p = 0.101). A high mucinous component was also an independent predictive factor for a shorter disease-free survival (p = 0.041, hazard ratio = 2.56) and distant recurrence-free survival (p = 0.001, hazard ratio = 5.74) according to a multivariate analysis., Conclusions: Because the mucinous components showed little correlation with local recurrence, mucinous cancer should not be a determining factor for chemoradiotherapy. However, the frequent occurrence of metachronous distant metastasis among patients with a high mucin component makes this a possible indicator for more robust postoperative adjuvant treatment and close surveillance of recurrence.

The 2014 World Health Organization classification calls for endometrial mucinous proliferations that display "confluent or cribriform architecture with even minimal atypia" in sampling specimens to be classified as carcinoma, and others whose features are not diagnostic of carcinoma to be categorized as atypical mucinous glandular proliferations (AMGPs). Herein, we evaluate follow-up findings in 41 cases that were classified as AMGP from our files. The average patient age was 46years (range, 37-59 years). Postbiopsy follow-up duration ranged from 15 to 109weeks (mean, 40 weeks). There was no follow-up resection in 12 patients (9 with repeat biopsies, all 9 with no clinical evidence of disease, mean follow-up of 43weeks), and 29 patients underwent a hysterectomy an average of 2.4months after the index biopsy. The distribution of pathologic findings in the uteri was as follows: no residual AMGP or carcinoma (5/29; 17%), AMGP (11/29; 38%), and adenocarcinoma (13/29; 45%). All adenocarcinomas were grade I and stage I, and histotypes were endometrioid (n=8), mucinous (n=3), and endometrioid with mucinous differentiation (n=2). Only 3 (23%) carcinomas were myoinvasive, of which 1 case, a mucinous carcinoma with a 40% endometrioid component, showed greater than 50% myometrial invasion. None of a wide array of morphologic features was significantly associated with a hysterectomy diagnosis of carcinoma (versus AMGP) on univariate analyses. In conclusion, our cohort of AMGP represents a biologically variable spectrum of lesions that includes mucinous hyperplastic proliferations as well as endometrioid and mucinous adenocarcinomas that are occasionally myoinvasive. Morphologic features that optimally stratified AMGP cases into clinically relevant subgroups were not identified., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Most patients with human intestinal spirochetosis (HIS; a colorectal bacterial infection caused by Brachyspira species) seem asymptomatic, and its pathogenicity remains unclear. Recently, alterations in mucin expression were reported in animal Brachyspira infection. The present question was "Is mucin expression altered in HIS?" Using antibodies for MUCs 1, 2, 4, 5AC, and 6, we immunohistochemically compared 215 specimens from 83 histology-confirmed HIS cases with 106 specimens from 26 non-HIS cases. Positive staining (which included even focal positive staining) was rated "high (+)" or "low (+)." Results were analyzed for 4 categories of lesions, and associations between MUC expression and spirochetal presence were also analyzed. In the "specimens without polyps or adenocarcinoma" category, high (+) MUC2 positivity was more frequent in HIS than in control. In the hyperplasia/serrated polyp category, in HIS (versus control), the MUC5AC positivity rate was lower, whereas high (+) MUC4 positivity was more frequent. In the conventional adenoma category, in HIS (versus control), the MUC1 positivity rate was lower, whereas both high (+) MUC2 positivity and high (+) MUC5AC positivity were less frequent. In the adenocarcinoma category, high (+) MUC2 positivity was more frequent in HIS than in control. Among the above mucins, only MUC1 positivity was significantly associated with an absence of the so-called fringe formation, an absence of spiral organisms within mucus, and an absence of strong immunopositive materials within the epithelial layer and within the subepithelial layer. The results suggest that Brachyspira infection or a related change in the microbiome may alter the large intestine mucin expression profile in humans., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose:: To measure the tissue sulfomucin and sialomucin content of the colon mucosa without fecal flow, subjected to intervention with curcumin, and the influence of the concentration used and the intervention time., Methods:: Thirty-six rats were subjected to proximal right colostomy and distal mucous fistula. They were divided into two groups according to whether sacrifice was performed two or four weeks after the intervention. Each group was divided into three subgroups according to the enema applied daily: saline alone; curcumin at 50 mg/kg/day or curcumin at 200 mg/kg/day. Acid mucins were diagnosed using the Alcian blue technique. The mucin content was quantified by means of computer-assisted image analysis. The significance level of 5% was used throughout (p < 0.05)., Results:: There were dose-related increases in the quantities of sulfomucins in the animals subjected to interventions with curcumin, both after two weeks (p < 0.00001) and after four weeks (p < 0.00001). There were increases in sialomucin quantity that were concentration-related (p < 0.00001) and time-related (p < 0.00001)., Conclusion:: Curcumin enemas increase the quantity of acid mucins in the intestinal flow in the excluded colon, with dose and time dependency.

Dermal deposits of mucin in the legs have been described associated with venous insufficiency. However, some degree of stasis dermatitis is generally common in aged individuals. Therefore, some amount of mucin is expected a priori in the reticular dermis of aged patients, even in the absence of clinical lesions. To test this hypothesis, the authors investigated the mucin in the legs of aged individuals without any dermatologic disease. Cutaneous samples were taken from the legs of 15 autopsy cases. A sample of the skin of the legs (either from the left or the right leg without any distinction being made) was randomly taken (without selecting any specific area or attending to macroscopical features). The skin samples were fixed in formaldehyde, and sections obtained from all samples were stained with hematoxylin and eosin, iron, and Alcian blue. Iron deposits were graded as 0/4 in 7 cases, as 1/4 in 4 cases, as 2/4 in 2 cases, and as 4/4 in 2 cases. Cases with greater deposits of iron also had other signs of stasis, such as neovascularization. All the samples scored 0 for dermal mucin deposits in the reticular dermis. The authors conclude that mucin deposits in the legs are not inherent to aging. Therefore, any mucin deposit in the reticular dermis, as well as expansion of the periadnexal dermis by mucin deposits, should be considered abnormal.

In the intestine, the mucosal immune system plays essential roles in maintaining homeostasis between the host and microorganisms, and protecting the host from pathogenic invaders. Epithelial cells produce and release a variety of biomolecules into the mucosa and lumen that contribute to immunity. In this review, we focus on a subset of these remarkable host-defense factors - enteric α-defensins, select lectins, mucins, and secretory immunoglobulin A - that have the capacity to bind microbes and thereby contribute to barrier function in the human gut. We provide an overview of the intestinal epithelium, describe specialized secretory cells named Paneth cells, and summarize our current understanding of the biophysical and functional properties of these select microbe-binding biomolecules. We intend for this compilation to complement prior reviews on intestinal host-defense factors, highlight recent advances in the field, and motivate investigations that further illuminate molecular mechanisms as well as the interplay between these molecules and microbes.

The authors present 11 cases of plexiform neurofibroma (PN) that featured a very characteristic type of cell appearing as multivacuolated mucin-filled cells (MMFC). The 11 cases were obtained after reviewing 109 cases of PN. Six out of 10 patients showed clinical features of neurofibromatosis type 1. The size of PN ranged from 0.8 cm to 11.5 cm in the largest dimension. The lesions represented classical PN in all cases with myxoid, hypocellular stroma. The MMFC were found within the most myxoid tumorous nodules and were haphazardly located, typically featuring a variably sized, multivacuolated cytoplasm divided by fine septa with a small polygonal nucleus on one side, which was often compressed or slightly indented by the cytoplasmic mucous substances. In many cases, the cells resembled a soccer ball or a jellyfish. In all tested cases (n = 9), the MMFC stained for CD34; six cases were also positive with GLUT-1 antibody, and two cases expressed Claudin-1, whereas S-100 protein was negative. For comparison, we have reviewed a series of randomly selected non-PN, malignant peripheral nerve sheath tumors (MPNST) and of cases featuring non-neoplastic nerve trunks in our files, in which no MMFC were encountered. MMFC seem to be unique to myxoid areas of PN, where they occur in about 10% of cases. Their exact histogenesis is unclear but they might represent an intermediate type of cell between perineurial cells and fibroblasts. The awareness of this cell type in PN is especially important in limited (small) biopsy specimens where their recognition may provide a clue for the correct diagnosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Mucin13 (MUC13) is a transmembrane glycoprotein that is aberrantly expressed in ovarian and gastro-intestinal tumors, but its role in renal cell carcinoma remains elusive. The purpose of this study is to evaluate the prognostic value of MUC13 expression in patients with non-metastatic clear cell renal cell carcinoma (ccRCC) after surgical resection., Results: MUC13 high expression was associated with high Fuhrman grade (p < 0.001), high SSIGN score (p = 0.011), early recurrence (p < 0.001) and poor survival (p < 0.001). Multivariate Cox regression analysis identified MUC13 expression as an independent prognostic factor for RFS and OS of ccRCC patients. A nomogram integrating MUC13 expression and other independent prognosticators was established to predict RFS and OS of ccRCC patients. Optimal agreement was shown between the predictions and observations in calibration curves., Materials and Methods: This study enrolled 410 postoperative non-metastatic ccRCC patients at a single institution. Clinicopathologic variables, recurrence-free survival (RFS), and overall survival (OS) were recorded. MUC13 expression was detected by immunohistochemical staining in tumor specimens. Association of MUC13 expression with clinicopathological factors was explored. Kaplan-Meier analysis was performed to compare survival curves. Univariate and multivariate Cox regression models were used to analyze the impact of prognostic factors on RFS and OS. A prognostic nomogram was constructed based on the independent prognostic factors identified by multivariate analysis., Conclusions: MUC13 high expression is a novel independent adverse prognostic factor of clinical outcome in non-metastatic ccRCC patients after surgery.

Background: Laryngeal cancer and oral cancer are not always correlated with genetic mutations, HPV infection, smoking, and alcohol abuse. In the absence of these risk factors, there is an increase on these cancers with a parallel increase of diabetes. The aim of this study is to verify if diabetes could be a risk factor for the laryngeal cancer., Methods: A questionnaire was given to a group of ninety laryngectomees to verify if these patients have presented diabetes and xerostomia before surgery. In two groups, diabetics and healthy persons, the values of the salivary mucins and the pH were evaluated. The results were statistically analysed using Fisher Exact Test and Chisquare Test Results: Diabetes is a risk factor: p= 0.0445 for laryngectomees male vs control group. Xerostomia inlaryngectomees male is a risk factor: p= 0.050. The values of mucins and pH in diabetic group show significant difference: p=0.05 vs control group Discussion: In all autoimmune diseases, a decrease in the value of pH and salivary flow consequently decreases the value of spinnbarkeit which measures the capacity of the mucous layer to adhere to the epithelium and alter the protective oral mucin layer. We find that diabetes is epidemiologically correlated with laryngeal cancer. In fact, only diabetes increases the concentration of salivary mucins with a formation of mucin layer even more reduced, and so completely ineffective in protecting the mucosa., Conclusions: The increase of mucin secretion in diabetes alters much the protective layer allowing the risk factors to promote cancer growth.

Purpose: To detect the expression of mucins in diverse benign and malignant cervical tissues of cervical disease., Materials and Methods: 158 cases of cervical tissues were collected. Sections were stained with monoclonal antibodies against MUC1, MUC2, MIUC4, MUC5AC, and MUC20 by immunohistochemistry., Results: Normal cervical epithelium showed high expr ession of MUC1I, MUC4, and MUC5AC, partial expression of MUC20, and no MUC2. With the development from chronic cervicitis, cervical intraepithelial neoplasia (CI7N) to cervical squamous cell carcinoma (SCC), the expression of MUC1, NMUC4, and MUC20 was statistically significant. The expression of MUCl was related with the depth of invasion and clinical stage of SCC. The positive rates of MUC4 and MUC20 were associated with the degree of differentiation and clinical stage of SCC. There was a correlation between the expression of MUC4, MUC 1, and MUC20 in cervical squamous lesions., Conclusion: Mucins may be involved in the development of cervical cancer.

The aim of this study was to compare the immunoexpression of epithelial mucins (MUCs) in salivary duct cysts, papillary cystadenomas, and mucoepidermoid carcinomas and to evaluate if any of these markers could be useful for differentiating between mucoepidermoid carcinoma and papillary cystadenoma. We also sought to validate the p63 expression pattern found to differentiate between mucoepidermoid carcinoma and papillary cystadenoma. Immunoexpression of MUC1, MUC2, MUC4, MUC7, and p63 was studied and quantified in 22 mucoepidermoid carcinomas, 12 papillary cystadenomas, and 3 salivary duct cysts. The immunohistochemical evaluation was collectively performed by 3 oral pathologists. Scores and trends in proportions were assessed using the nonparametric Wilcoxon-Mann-Whitney rank sum test. Mucoepidermoid carcinomas, papillary cystadenomas, and salivary duct cysts demonstrated variable MUC expression patterns. All tumors were positive for p63 immunoexpression with p63 labeling in salivary duct cysts and papillary cystadenomas (15/15) limited to the basal layers of the cystic spaces, whereas in mucoepidermoid carcinomas (22/22) the p63 labeling extended throughout the suprabasal layers (p < 0.001). This study adds more confirmatory data to validate that the reactivity pattern of p63 protein can be used in distinguishing between papillary cystadenoma and low-grade mucoepidermoid carcinoma. Although positive reactivity in a tumor with MUC1 and MUC4 was inconclusive, negative reactivity suggests the diagnosis of a benign PC or SDC., Competing Interests: None.