The mucus layer protects airway epithelia from damage by noxious agents. Intriguingly, Bordetella pertussis bacteria provoke massive mucus production by nasopharyngeal epithelia during the initial coryza-like catarrhal stage of human pertussis and the pathogen transmits in mucus-containing aerosol droplets expelled by sneezing and post-nasal drip-triggered cough. We investigated the role of the cAMP-elevating adenylate cyclase (CyaA) and pertussis (PT) toxins in the upregulation of mucin production in B. pertussis-infected airway epithelia. Using human pseudostratified airway epithelial cell layers cultured at air-liquid interface (ALI), we show that purified CyaA and PT toxins (100 ng/mL) can trigger production of the major airway mucins Muc5AC and Muc5B. Upregulation of mucin secretion involved activation of the cAMP response element binding protein (CREB) and was blocked by the 666-15-Calbiochem inhibitor of CREB-mediated gene transcription. Intriguingly, a B. pertussis mutant strain secreting only active PT and producing the enzymatically inactive CyaA-AC- toxoid failed to trigger any important mucus production in infected epithelial cell layers in vitro or in vivo in the tracheal epithelia of intranasally infected mice. In contrast, the PT- toxoid-producing B. pertussis mutant secreting the active CyaA toxin elicited a comparable mucin production as infection of epithelial cell layers or tracheal epithelia of infected mice by the wild-type B. pertussis secreting both PT and CyaA toxins. Hence, the cAMP-elevating activity of B. pertussis-secreted CyaA was alone sufficient for activation of mucin production through a CREB-dependent mechanism in B. pertussis-infected airway epithelia in vivo.

• MeSH
• Adenylate Cyclase Toxin toxicity   MeSH
• Bordetella pertussis metabolism   pathogenicity   MeSH
• Cell Line MeSH
• Respiratory System metabolism   microbiology   MeSH
• Epithelial Cells metabolism   microbiology   MeSH
• Humans MeSH
• Mucin 5AC metabolism   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Whooping Cough metabolism   microbiology   MeSH
• Cyclic AMP Response Element-Binding Protein metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Mucin and mucin-like material are features of mucinous tubular and spindle renal cell carcinoma (MTS RCC) but are rarely seen in papillary renal cell carcinoma (PRCC). We reviewed 1311 PRCC and identified 7 tumors containing extracellular and/or intracellular mucinous/mucin-like material (labeled as PRCCM). We analyzed these using morphological, histochemical, immunohistochemical, and molecular genetic methods (arrayCGH, FISH). Clinical data were available for six of the seven patients (five males and one female, age range 61-78 years). Follow-up was available for four patients (2-4 years); one patient died of widespread metastases. Tumor size ranged from 3 to 5 cm (mean 3.8). Of all cases, histological architecture showed a predominantly papillary pattern. Mucin or mucin-like was extracellular in one, intracellular in three, and both intra/extracellular in three cases. All tumors were positive for AMACR, vimentin, and OSCAR, while CK7 was positive in four. Mucicarmine stain was positive in all cases, PAS in six and Alcian blue in three cases. Five tumors were positive for MUC 1, but none were positive for MUC 2, MUC 4, or MUC 6. In only four cases, genetic analysis could be performed. Gain of chromosomes 7 and 17 was found in two cases; gain of 17 only was found in one case. Loss of heterozygosity of 3p was found in one case together with polysomy of chromosomes 7 and 17. No abnormalities of VHL, fumarate dehydrogenase, and TFE3 genes were detected. We conclude that PRCCM is a rare but challenging subtype of RCC that deserves to be further studied. In all the tumors, the mucin-like material was found in those stained with mucicarmin, but other conventional and immunohistochemical stains did not reveal consistent features of a single mucin. The molecular-genetic profile of these tumors was most consistent with that of typical papillary RCC, although one case had mixed genetic features of papillary and clear RCC. PRCCM has metastatic potential, as evidenced by one case with widespread metastases. It remains to be determined whether PRCCM represents a unique tumor subtype, deserving to be distinguished from other subtypes of PRCC.

• MeSH
• Antigens, Neoplasm metabolism   MeSH
• In Situ Hybridization, Fluorescence methods   MeSH
• Immunohistochemistry methods   MeSH
• Carcinoma, Renal Cell genetics   metabolism   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mucins analysis   MeSH
• Biomarkers, Tumor analysis   MeSH
• Kidney Neoplasms genetics   metabolism   pathology   MeSH
• Carcinoma, Papillary pathology   MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Prominin-1 (CD133) is physiologically expressed at the apical membranes of secretory (serous and mucous) and duct cells of major salivary glands. We investigated its expression in various human salivary gland lesions using two distinct anti-prominin-1 monoclonal antibodies (80B258 and AC133) applied on paraffin-embedded sections and characterized its occurrence in saliva. The 80B258 epitope was extensively expressed in adenoid cystic carcinoma, in lesser extent in acinic cell carcinoma and pleomorphic adenoma, and rarely in mucoepidermoid carcinoma. The 80B258 immunoreactivity was predominately detected at the apical membrane of tumor cells showing acinar or intercalated duct cell differentiation, which lined duct- or cyst-like structures, and in luminal secretions. It was observed on the whole cell membrane in non-luminal structures present in the vicinity of thin-walled blood vessels and hemorrhagic areas in adenoid cystic carcinoma. Of note, AC133 labeled only a subset of 80B258-positive structures. In peritumoral salivary gland tissues as well as in obstructive sialadenitis, an up-regulation of prominin-1 (both 80B258 and AC133 immunoreactivities) was observed in intercalated duct cells. In most tissues, prominin-1 was partially co-expressed with two cancer markers: carcinoembryonic antigen (CEA) and mucin-1 (MUC1). Differential centrifugation of saliva followed by immunoblotting indicated that all three markers were released in association with small membrane vesicles. Immuno-isolated prominin-1-positive vesicles contained CEA and MUC1, but also exosome-related proteins CD63, flotillin-1, flotillin-2 and the adaptor protein syntenin-1. The latter protein was shown to interact with prominin-1 as demonstrated by its co-immunoisolation. A fraction of saliva-associated prominin-1 appeared to be ubiquitinated. Collectively, our findings bring new insights into the biochemistry and trafficking of prominin-1 as well as its immunohistochemical profile in certain types of salivary gland tumors and inflammatory diseases.

• MeSH
• Cell Membrane metabolism   MeSH
• Antigens, CD metabolism   MeSH
• Glycoproteins metabolism   secretion   MeSH
• Carcinoembryonic Antigen metabolism   MeSH
• Humans MeSH
• Mucin-1 metabolism   MeSH
• Salivary Gland Neoplasms metabolism   pathology   MeSH
• Peptides metabolism   secretion   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• Sialadenitis metabolism   pathology   MeSH
• Saliva metabolism   MeSH
• Neoplasm Grading MeSH
• Syntenins metabolism   MeSH
• Ubiquitination * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

In mammary pathology, adenosis tumor is defined as a clinically recognizable lesion that histologically primarily consists of adenosis, but also exhibits various combinations of diverse epithelial changes seen in other benign breast diseases. A lesion that occurred in the anogenital area of a 46-year-old woman and apparently arose in anogenital mammary-like glands is described and which, in our opinion, is best classified as adenosis tumor. A biopsy revealed a well-demarcated, unencapsulated lesion surrounded by compressed fibrous tissue forming a pseudocapsule. Several histological patterns within the same tumor mass were recognizable: sclerosing adenosis-like changes, variably sized microcysts and cysts, some with rare short papillary projections having hyalinized cores, rare tubular structures exhibiting epithelial features reminiscent of simple ductal hyperplasia, areas with oxyphilic (apocrine) metaplasia, and clear cell epithelial changes resembling mucinous metaplasia. Decapitation secretion was notable in many lumens. Rare lumens were filled with foamy macrophages. There were also focal clear cell changes of myoepithelial cells. The stroma was paucicellular and sclerotic in some foci and composed of myofibroblasts and myxoid in others. Calponin, actins, and p63 stained myoepithelial cells. The cells in the oxyphilic (apocrine) metaplasia areas stained for mitochondrial antigen and Bcl-2. Antibodies to progesterone and estrogen receptor stained approximately 50 and 20% of the epithelial cell population, respectively. Human androgen receptor gene analysis yielded a monoclonal pattern. As our case exhibited a number of patterns identical to those seen in diverse benign breast diseases, its classification as adenosis tumor seems justifiable. This cutaneous perianal lesion is indistinguishable microscopically from its mammary analogue and was clinically detectable.

• MeSH
• Receptors, Androgen metabolism   MeSH
• Clone Cells metabolism   pathology   MeSH
• Fibrocystic Breast Disease metabolism   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Mammary Glands, Human metabolism   pathology   MeSH
• Biomarkers, Tumor metabolism   MeSH
• Anus Neoplasms surgery   metabolism   pathology   MeSH
• Skin Neoplasms surgery   metabolism   pathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH