ABSTRACT
Maspin is a member of the serpin family of protease inhibitors. It is a 42 kDa cytoplasmic protein that is reported to have tumour suppressor activity. The loss of maspin gene expression is correlated with increased invasiveness and the risk of metastases in breast cancer. We studied maspin expression in primary melanoma lesions obtained from 76 patients. Immunostaining of 5 pm sections for maspin expression was obtained using the citrate antigen retrieval method. The extent of immunostaining was scored by recording the proportion of immunoreactive cells and the intensity of immunostaining. Our results demonstrated that maspin expression was down-regulated in intermediate thickness and thick melanoma lesions compared with thin lesions. These results suggest that loss of maspin expression might play a role in melanoma progression, invasion and metastatic dissemination. Further studies are needed to clarify the clinicopathological significance of maspin expression in melanoma.
Subject(s)
Gene Expression Regulation, Neoplastic , Gene Expression , Melanoma/metabolism , Melanoma/pathology , Serpins/metabolism , Adult , Aged , Aged, 80 and over , Disease Progression , Down-Regulation , Female , Genes, Tumor Suppressor , Humans , Immunohistochemistry , Male , Middle AgedSubject(s)
Mucinoses/pathology , Adult , Antimalarials/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Male , Mucinoses/drug therapy , ThoraxSubject(s)
Analgesics, Opioid/adverse effects , Panniculitis/chemically induced , Pentazocine/adverse effects , Aged, 80 and over , Analgesics, Opioid/administration & dosage , Buttocks , Calcification, Physiologic , Female , Humans , Injections, Subcutaneous , Pentazocine/administration & dosage , ThighABSTRACT
BACKGROUND: Pemphigus vulgaris (PV, OMIM 169610) is a severe blistering disorder of the skin and mucous membranes, caused by the production of autoantibodies directed against the epithelial adhesive protein desmoglein 3. Although an association between PV and HLA class II alleles has been established, the genetic factors predisposing to the disease remain poorly understood, the rarity of PV hampering the recruitment of substantial patient cohorts. OBJECTIVES: To investigate DSG3 as a candidate PV susceptibility gene. METHODS: We examined five DSG3 single nucleotide polymorphisms (rs8085532, rs3911655, rs3848485, rs3794925 and rs1466379) in two case-control datasets respectively originating from the U.K. (62 PV patients, 154 controls) and northern India (28 patients, 98 controls). RESULTS: In the U.K. sample, we observed a significant association between PV and the DSG3*TCCTC haplotype (Fisher's exact test P = 0.002). A related haplotype (DSG3*TCCCC) was associated with PV in the Indian dataset (P = 0.002). We also found that all British and Indian patients bearing DSG3 risk haplotypes carried at least one copy of a PV-associated HLA allele. CONCLUSIONS: These results suggest that genetic variation of DSG3 may be an additive risk factor predisposing to PV and warrant further investigations of this gene.
