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E Yiasemides,
N Trisnowati,
J Su,
N Dang,
S Klingberg, P Marr,
W Melbourne,
K Tran,
C W Chow,
D Orchard,
G Varigos,
D F Murrell
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ABSTRACT: Epidermolysis bullosa simplex (EBS), the most common subtype of EB, is usually inherited as an autosomal dominant trait caused by mutations in either the keratin 5 (KRT5) or keratin 14 (KRT14) genes. Recessive EBS (R-EBS) is extremely rare.
We present the first Australian patient diagnosed with R-EBS, to our knowledge, and a comprehensive review of genotypes and phenotypes of R-EBS reported cases.
The female proband, of Turkish descent with consanguineous parentage, was referred to us at the age of 8 years. Clinically, she had a severe phenotype including generalized blisters, mucosal involvement and EB naevi. Immunofluorescence mapping and electron microscopy were consistent with a diagnosis of EBS. Staining for Keratin 14 (K14) was negative. The basal layer, however, reacted with monoclonal antibodies to keratins 6 (K6) and 16 (K16). Mutation screening from genomic DNA showed that the proband was homozygous for the truncation mutation Y204X in exon 3 of KRT14, and both unaffected parents were heterozygous for a single KRT14 Y204X mutation. The phenotype of our patient is reported in more detail and with longer follow-up than those of others published in the literature.
The proband's phenotype was severe as an infant but improved with age, suggesting that an alternative keratin is pairing with K5 in her skin to compensate for the loss of K14--a novel biological compensatory mechanism. It is interesting that K6 and K16 were expressed, as these are normally positive in hyperproliferative skin disorders.
Clinical and Experimental Dermatology 09/2008; 33(6):689-97. · 1.20 Impact Factor
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Journal of Investigative Dermatology 06/2005; 124(5):1083-5. · 6.31 Impact Factor
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ABSTRACT: Endogenous histamine has been shown to effect growth mechanisms in experimental mammary carcinomas via H2 membrane receptors (Cricco et al, 1994). Both H1 and H2 binding sites are present in human mammary glands but only 75% malignant carcinomas express H2 receptors (Lemos et al, 1995). The presence of mast cells around tumour tissue raises questions concerning the source of histamine in breast tumour tissue. While cimetidine, an H2 antagonist, has been shown to influence the presence of tumour infiltrating lymphocytes (TIL) in colorectal cancer (Adams and Morris, 1994, 1997) that was not found to be the case in breast cancer (Ng et al, 1995). In recent studies tumour cell proliferation, as measured by Ki-67 antibody labelling, has been seen as an additional prognostic indicator in breast cancer (Railo et al, 1993, 1997; Ferno, 1998; Schauer et al, 1998). We investigated the possibility that cimetidine may influence tumour proliferation by blocking the growth-promoting effects of histamine. No relationship between preoperative cimetidine administration and tumour cell proliferation was seen overall. A weak correlation was seen between tissue histamine content and mast cell count which was not influenced by cimetidine. Tumour cell proliferation correlated well with other prognostic indicators such as grade and differentiation.
British Journal of Cancer 02/2000; 82(1):167-70. · 5.04 Impact Factor
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ABSTRACT: To determine the variation in p53 protein expression in phyllodes tumours and fibroadenomas of the breast.
Fifteen phyllodes tumours (six malignant, nine benign) and 20 fibroadenomas were examined for p53 expression by immunohistochemistry. Five of the six malignant phyllodes tumours showed moderate or strong p53 positivity at sites of peri-epithelial stromal condensation and atypia. All 20 fibroadenomas, nine benign phyllodes tumours and one malignant phyllodes tumour showed either negativity or focal weak nuclear positivity of scattered stromal cells.
Increased p53 immunoreactivity is present in malignant phyllodes tumours in contrast to benign phyllodes tumours and fibroadenomas. Malignant phyllodes tumours display a distinctive pattern of p53 immunostaining which may be of diagnostic value. These findings suggest that p53 protein may be important in the progression of benign to malignant phyllodes tumours.
Histopathology 07/1999; 34(6):491-6. · 3.08 Impact Factor
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ABSTRACT: The gene Nm23 is thought to play a role in the suppression of tumour metastasis. Reduced expression of Nm23 is seen in a number of human cancers, and is associated with increased metastasis and reduced survival, most strongly in ductal breast and colorectal carcinomas.
Nm23 gene expression was compared in gastric carcinoma and normal gastric mucosa. Twenty-three gastric carcinomas were graded for differentiation as either well, moderately or poorly differentiated. Metastatic deposits from seven of the cases were also examined, along with 10 samples of normal gastric mucosa. Specimens were incubated with a murine monoclonal antibody against the protein product of Nm23, and examined by immunohistochemical staining. A semiquantitative immunostaining index was used.
All normal mucosa showed moderate to strong staining; 8 of 15 poorly differentiated carcinomas showed absent or weak staining; 1 of 6 moderately differentiated carcinomas stained weakly. Both well-differentiated carcinomas stained strongly; 1 of 7 metastatic deposits stained weakly. The difference in Nm23 expression between normal mucosa and carcinomas was statistically significant (P=0.024). However, there was no statistically significant difference between the three grades of carcinomas (P=0.51), or between primary and metastatic tumour (P=0.25, all by Chi-squared test).
These results suggest that Nm23 may have a role in gastric carcinoma pathogenesis, but do not show a correlation with metastasis. A larger study, involving detailed clinical staging and follow-up, may be of benefit.
Australian and New Zealand Journal of Surgery 04/1998; 68(3):180-2.
