ABSTRACT
Mucin core protein (MUC) 5AC is a gel-forming glycoprotein that is expressed in different types of tumour cells. MUC5AC expression in cultured cells is regulated through the extracellular matrix and through remodelling by other membranous proteins such as type IV collagen (COL4) and E-cadherin. However, it has not been elucidated whether COL4 and E-cadherin affect MUC5AC expression in tumours in vivo. Here, by analysing a single individual with concomitant neoplasms in the skin [extramammary Paget disease (EMPD)] and the stomach (gastric cancer), we show that MUC5AC expression is reduced in COL4 and membranous E-cadherin-expressing EMPD specimens whereas MUC5AC is not abolished in gastric cancer with COL4 negativity and E-cadherin cytoplasmic localization. As the EMPD and gastric cancer specimens were derived from a single patient, each specimen had the same genetic background. These in vivo results support previous in vitro studies which showed that COL4 and E-cadherin downregulated MUC5AC expression. Our study suggests that concomitant neoplasms in different organs of the same individual can serve as a strong tool for uncovering functional diversity in tumour markers in distinct cancer cells.
Subject(s)
Biomarkers, Tumor/metabolism , Cadherins/physiology , Collagen Type IV/physiology , Skin Neoplasms/metabolism , Stomach Neoplasms/metabolism , Aged , Down-Regulation/physiology , Humans , Male , Mucin 5AC/metabolism , Neoplasms, Multiple Primary/metabolism , Paget Disease, Extramammary/metabolism , Penile Neoplasms/metabolismSubject(s)
Graft vs Host Disease/immunology , Hematopoietic Stem Cell Transplantation/adverse effects , Histiocytosis, Non-Langerhans-Cell/immunology , Female , Graft vs Host Disease/diagnosis , Graft vs Host Disease/pathology , Hematopoietic Stem Cells/immunology , Histiocytosis, Non-Langerhans-Cell/diagnosis , Histiocytosis, Non-Langerhans-Cell/pathology , Humans , Leukemia, Myeloid, Acute/therapy , Macrophages/immunology , Skin/cytology , Skin/immunology , Skin/pathology , Transplantation, Homologous/adverse effects , Young AdultSubject(s)
Autoantibodies/metabolism , Mouth Mucosa/immunology , Pemphigoid, Benign Mucous Membrane/diagnosis , Aged , Aged, 80 and over , Autoantigens/metabolism , Biomarkers/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Pemphigoid, Benign Mucous Membrane/immunologySubject(s)
Desmoglein 1/immunology , Desmoglein 1/metabolism , Pemphigus/immunology , Adult , Autoantibodies , Humans , Male , Pemphigus/pathologySubject(s)
Alprostadil/adverse effects , Peripheral Vascular Diseases/chemically induced , Vasodilator Agents/adverse effects , Acute Disease , Administration, Intravenous , Aged , Alprostadil/administration & dosage , Humans , Male , Pyoderma Gangrenosum/drug therapy , Remission, Spontaneous , Vasodilator Agents/administration & dosageABSTRACT
Mucous membrane pemphigoid (MMP) is a mucous membrane-dominated, subepidermal autoimmune blistering disease in which autoantibodies usually react with the C-terminal domain of type XVII collagen (COL17) or with laminin-332. Only a few cases of MMP with widespread blisters have been reported. Serologically, IgA and IgG class autoantibodies directed against COL17 or IgG autoantibodies directed against laminin-332 in patients with MMP have been well documented. MMP cases in which IgA reacts with laminin-332, however, are extremely rare. We report a case of MMP in a 67-year-old man. Clinical examination revealed extensive mucosal lesions as well as generalized blisters and erosions that healed with scar formation. The disease was intractable to treatment with systemic steroids. Interestingly, in addition to IgG directed against laminin-332 and the noncollagenous 16A (NC16A) and C-terminal domains of COL17, circulating IgA reacting with laminin-332 and with the NC16A domain of COL17 was also detected. This is the first MMP case with circulating IgA and IgG autoantibodies against both laminin-332 and COL17.
Subject(s)
Autoantibodies/immunology , Autoantigens/immunology , Immunoglobulin A/immunology , Immunoglobulin G/immunology , Laminin/immunology , Non-Fibrillar Collagens/immunology , Pemphigoid, Benign Mucous Membrane/immunology , Aged , Blister/immunology , Humans , Immunoblotting , Male , Microscopy, Fluorescence , Collagen Type XVIISubject(s)
Clonazepam/adverse effects , Drug Eruptions , Lichenoid Eruptions/chemically induced , Female , Humans , Middle AgedSubject(s)
Keratin-6/genetics , Mutation , Pachyonychia Congenita/genetics , Child , Female , Humans , Male , PedigreeABSTRACT
Inherited ichthyoses are rare genodermatoses caused by mutations in the genes involved in epidermal development. Although there have been case reports on patients with ichthyosis who developed skin malignancies, it is still unknown whether or not patients with ichthyosis have an increased risk of skin malignancies. Here, we review case series of skin malignancies in patients with ichthyosis and show biological findings which might lead to cancer susceptibility. A survey of the literature revealed 28 cases of inherited ichthyoses with skin malignancy, including 12 cases of keratitis-ichthyosis-deafness (KID) syndrome, seven of autosomal recessive congenital ichthyosis, three of Netherton syndrome and six of miscellaneous ichthyosis. Twenty-four of the 28 cases developed single or multiple squamous cell carcinomas (SCCs). The age at diagnosis of the first skin malignancy ranged from 15 to 54 years. As patients with these particular subtypes of ichthyosis seem to be prone to skin malignancies, including SCC, at an unusually young age, routine cancer surveillance of these patients is strongly recommended.