23 results on '"Perrett, C."'
Search Results
2. Inherited palmoplantar keratodermas: the heart of the matter.
- Author
-
Thomas LJ, Freeman A, O'Toole EA, McGrath JA, and Perrett CM
- Subjects
- Adult, Humans, Male, Cardiomyopathies diagnosis, Hair Diseases genetics, Hand Dermatoses genetics, Hand Dermatoses pathology, Keratoderma, Palmoplantar genetics, Keratoderma, Palmoplantar pathology, Ventricular Dysfunction, Left diagnosis
- Published
- 2018
- Full Text
- View/download PDF
3. Cirsoid aneurysm: a clinicopathological reminder.
- Author
-
Veitch D, Kravvas G, and Perrett CM
- Subjects
- Diagnosis, Differential, Humans, Male, Middle Aged, Aneurysm pathology, Arteriovenous Malformations pathology, Hand Dermatoses pathology
- Published
- 2015
- Full Text
- View/download PDF
4. Primary eccrine carcinoma treated with Mohs micrographic surgery and adjuvant radiotherapy.
- Author
-
Chandrakumar A, Veitch D, Proctor I, Hughes S, and Perrett CM
- Subjects
- Aged, 80 and over, Female, Humans, Radiotherapy, Adjuvant, Scalp, Treatment Outcome, Carcinoma therapy, Head and Neck Neoplasms therapy, Mohs Surgery, Sweat Gland Neoplasms therapy
- Published
- 2015
- Full Text
- View/download PDF
5. Treatment of multiple periocular eccrine hidrocystomata: is botulinum toxin or electrocautery more effective?
- Author
-
Meys R and Perrett CM
- Subjects
- Adult, Humans, Male, Treatment Outcome, Botulinum Toxins therapeutic use, Electrocoagulation methods, Eyelid Neoplasms therapy, Hidrocystoma therapy, Neurotoxins therapeutic use, Sweat Gland Neoplasms therapy
- Published
- 2015
- Full Text
- View/download PDF
6. A crusted lesion on the penis.
- Author
-
Wilmot MC, Perrett CM, Calonje E, Weir J, and Bunker CB
- Subjects
- Diagnosis, Differential, Humans, Male, Middle Aged, Acantholysis pathology, Penile Diseases pathology, Skin Diseases pathology
- Published
- 2014
- Full Text
- View/download PDF
7. Expression of DNA mismatch repair proteins and MSH2 polymorphisms in nonmelanoma skin cancers of organ transplant recipients.
- Author
-
Perrett CM, Harwood CA, McGregor JM, Warwick J, Cerio R, and Karran P
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Azathioprine therapeutic use, Base Pair Mismatch genetics, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Carcinoma, Squamous Cell metabolism, Female, Humans, Immunosuppressive Agents therapeutic use, Male, Microsatellite Instability, Middle Aged, MutL Protein Homolog 1, MutS Homolog 2 Protein metabolism, Nuclear Proteins genetics, Nuclear Proteins metabolism, Polymorphism, Genetic genetics, Skin Neoplasms metabolism, Carcinoma, Squamous Cell genetics, DNA Mismatch Repair genetics, MutS Homolog 2 Protein genetics, Organ Transplantation adverse effects, Skin Neoplasms genetics
- Abstract
Background: Organ transplant recipients (OTRs) have an increased risk of skin cancer. Treatment with azathioprine, commonly used in post-transplant immunosuppressive regimens, results in incorporation of 6-thioguanine (6-TG) into DNA. Mismatch repair (MMR)-defective cells are resistant to killing by 6-TG. Azathioprine exposure confers a survival advantage on MMR-defective cells, which are hypermutable and may therefore contribute to azathioprine-related nonmelanoma skin cancer, a phenomenon we have previously demonstrated in transplant-associated sebaceous carcinomas. The MSH2 protein is an important component of DNA MMR. The -6 exon 13 T>C MSH2 polymorphism is associated with impaired MMR, drug resistance and certain cancers., Objectives: To investigate (i) whether loss of MMR protein expression and microsatellite instability are over-represented in squamous cell carcinomas (SCCs) from OTRs on azathioprine compared with SCCs from immunocompetent patients, and (ii) whether the MSH2 -6 exon 13 polymorphism is over-represented in OTRs with skin cancer on azathioprine., Methods: (i) Immunohistochemical staining was used to assess expression of the MMR proteins MSH2 and MLH1 in cutaneous SCCs from OTRs on azathioprine and from immunocompetent patients. (ii) Blood samples from OTRs on azathioprine with and without skin cancer were genotyped for the -6 exon 13 MSH2 polymorphism., Results: (i) MSH2 and MLH1 protein expression was not altered in SCCs from OTRs on azathioprine and there was no difference in expression between SCCs from OTRs and immunocompetent patients. (ii) There was no association between MSH2 polymorphism genotype frequency and OTR skin cancer status., Conclusions: Despite previous findings in transplant-associated sebaceous carcinomas, defective MMR and the -6 exon 13 MSH2 polymorphism are unlikely to play a significant role in the development of SCC in OTRs on azathioprine.
- Published
- 2010
- Full Text
- View/download PDF
8. Azathioprine treatment photosensitizes human skin to ultraviolet A radiation.
- Author
-
Perrett CM, Walker SL, O'Donovan P, Warwick J, Harwood CA, Karran P, and McGregor JM
- Subjects
- Adult, Case-Control Studies, Dose-Response Relationship, Radiation, Epidermis radiation effects, Female, Graft Rejection drug therapy, Humans, Male, Middle Aged, Thioguanine adverse effects, Treatment Outcome, Azathioprine adverse effects, DNA Damage, Immunosuppressive Agents adverse effects, Photosensitivity Disorders chemically induced, Skin Neoplasms etiology, Ultraviolet Therapy adverse effects
- Abstract
Background: Azathioprine is used to treat a variety of conditions and to prevent graft rejection in organ transplant recipients (OTRs)., Objectives: To investigate clinically our previous finding that azathioprine metabolites interact with ultraviolet (UV) A radiation to form promutagenic oxidative DNA damage and to determine whether this may be causal or contributory to the development of excess skin cancers post-transplantation., Methods: The clinical corollary of these data were investigated. Five patients were recruited and the minimal erythema dose (MED) for UVB, UVA and solar-simulated radiation (SSR) was determined for each person before, and at least 12 weeks after, starting azathioprine therapy., Results: In all five patients azathioprine treatment was associated with an increased UVA and SSR sensitivity of the skin and a significant reduction in MEDs for UVA and SSR. We found no change in UVB-induced erythema or MED. In addition, we found that DNA from the skin of patients on azathioprine contains 6-thioguanine (6-TG)., Conclusions: Our findings confirm the presence of DNA 6-TG in the skin of those taking therapeutic doses of azathioprine and provide support for the hypothesis that DNA damage occurs when DNA 6-TG interacts with UVA, resulting in abnormal cutaneous photosensitivity.
- Published
- 2008
- Full Text
- View/download PDF
9. Vulval intraepithelial neoplasia and periungual Bowen's disease concordant for mucosal (HPV-34) and epidermodysplasia verruciformis (HPV-21) human papillomavirus types.
- Author
-
Ekeowa-Anderson AL, Harwood CA, Perrett CM, Sahota A, Annan H, Ran H, Leigh IM, and Gibbon KL
- Subjects
- Adult, Female, Humans, Bowen's Disease virology, Fingers virology, Papillomaviridae isolation & purification, Papillomavirus Infections virology, Skin Neoplasms virology, Vulvar Neoplasms virology
- Abstract
Human papillomavirus (HPV) infection is associated with genital malignancy and specific cutaneous malignancies. We report a case of an HPV-associated concurrent vulval intraepithelial neoplasia and periungual Bowen's disease in a young immunocompetent Afro-Caribbean woman with no known risk factors for either disease. HPV genotyping studies detected multiple alpha and beta papillomaviruses with concordance for HPV-34 [a high-risk (HR) mucosal type], and HPV-21 [an epidermodyslasia verruciformis (EV) type] in both vulval and finger tissue. Although the HR-mucosal viruses detected are likely to have a pathogenic role in vulval intraepithelial neoplasia, this is the first report of concordance for EV HPV types in both genital and nongenital skin premalignancies. This case, in the context of accumulating epidemiological and experimental data in cutaneous SCC, raises the question of whether EV HPV may contribute to vulval malignancy, and further study is merited.
- Published
- 2007
- Full Text
- View/download PDF
10. Treatment of post-transplant premalignant skin disease: a randomized intrapatient comparative study of 5-fluorouracil cream and topical photodynamic therapy.
- Author
-
Perrett CM, McGregor JM, Warwick J, Karran P, Leigh IM, Proby CM, and Harwood CA
- Subjects
- Administration, Topical, Aged, Aminolevulinic Acid administration & dosage, Bowen's Disease drug therapy, Bowen's Disease etiology, Double-Blind Method, Female, Humans, Keratosis drug therapy, Keratosis etiology, Male, Middle Aged, Risk Factors, Treatment Outcome, Antimetabolites, Antineoplastic therapeutic use, Carcinoma in Situ drug therapy, Fluorouracil therapeutic use, Photochemotherapy methods, Precancerous Conditions drug therapy, Skin Neoplasms drug therapy, Transplantation adverse effects
- Abstract
Background: Organ transplant recipients (OTR) are at high risk of developing nonmelanoma skin cancer and premalignant epidermal dysplasia (carcinoma in situ/ Bowen's disease and actinic keratoses). Epidermal dysplasia is often widespread and there are few comparative studies of available treatments., Objectives: To compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant epidermal dysplasia., Methods: Eight OTRs with epidermal dysplasia were recruited to an open-label, single-centre, randomized, intrapatient comparative study. Treatment with two cycles of topical MAL PDT 1 week apart was randomly assigned to one area of epidermal dysplasia, and 5-FU cream was applied twice daily for 3 weeks to a clinically and histologically comparable area. Patients were reviewed at 1, 3 and 6 months after treatment. The main outcome measures were complete resolution rate (CRR), overall reduction in lesional area, treatment-associated pain and erythema, cosmetic outcome and global patient preference., Results: At all time points evaluated after completion of treatment, PDT was more effective than 5-FU in achieving complete resolution: eight of nine lesional areas cleared with PDT (CRR 89%, 95% CI: 0.52-0.99), compared with one of nine lesional areas treated with 5-FU (CRR 11%, 95% CI: 0.003-0.48) (P = 0.02). The mean lesional area reduction was also proportionately greater with PDT than with 5-FU (100% vs. 79% respectively). Cosmetic outcome and patient preference were also superior in the PDT-treated group., Conclusions: Compared with topical 5-FU, MAL PDT was a more effective and cosmetically acceptable treatment for epidermal dysplasia in OTRs and was preferred by patients. Further studies are now required to confirm these results and to examine the effect of treating epidermal dysplasia with PDT on subsequent development of squamous cell carcinoma in this high risk population.
- Published
- 2007
- Full Text
- View/download PDF
11. Treatment of basal cell carcinoma with topical methylaminolaevulinate photodynamic therapy in an organ-transplant recipient.
- Author
-
Perrett CM, Tan SK, Cerio R, Goldsmith PC, McGregor JM, Proby CM, and Harwood CA
- Subjects
- Administration, Topical, Aminolevulinic Acid administration & dosage, Female, Humans, Middle Aged, Skin Neoplasms drug therapy, Treatment Outcome, Aminolevulinic Acid analogs & derivatives, Carcinoma, Basal Cell drug therapy, Liver Transplantation, Nose Neoplasms drug therapy, Photochemotherapy methods, Photosensitizing Agents administration & dosage
- Published
- 2006
- Full Text
- View/download PDF
12. Familial prevalence of uterine fibroids is associated with distinct clinical and molecular features.
- Author
-
Okolo SO, Gentry CC, Perrett CW, and Maclean AB
- Subjects
- Adult, Case-Control Studies, Dysmenorrhea epidemiology, Dysmenorrhea metabolism, Dysmenorrhea pathology, Family Health, Female, Genetic Markers, Humans, Immunohistochemistry, Incidence, Leiomyoma metabolism, Prevalence, Surveys and Questionnaires, Vascular Endothelial Growth Factor A metabolism, Leiomyoma epidemiology, Leiomyoma pathology
- Abstract
Background: Although uterine fibroids are very common, their pathogenesis and clinical behaviour are poorly understood. Since they may be prevalent in some families, we investigated whether such a prevalence was associated with distinctive clinical and molecular features., Methods: A case-control questionnaire study of 300 multi-ethnic women with uterine fibroids at a London university hospital was undertaken, with review of case notes and immunohistochemical determination of vascular endothelial growth factor (VEGF-A) in fibroids., Results: When compared with families with sporadic fibroids, familial prevalence of fibroids was associated with a higher incidence of abdominal swelling (59.1% versus 41.6%; P=0.037), menorrhagia (84.4% versus 51.9%; P=0.042), dysmenorrhoea (64.4% versus 46.3%; P=0.004), dyspareunia (43.2% versus 27.9%; P=0.012) and family history of cancers (52.3% versus 32.4%; P<0.01). The fibroids were also more multiple (mean +/- SEM: 7 +/- 0.86 versus 3 +/- 0.42; P<0.011) and strong VEGF-A expression in fibroids was more common in the familial group (64% versus 28%). Racial distribution was the same in both groups (blacks 49%, whites 33.4%, others 18.6%)., Conclusions: Familial prevalence of uterine fibroids is associated with distinct clinical and molecular features that differ from those found when fibroids occur sporadically in families.
- Published
- 2005
- Full Text
- View/download PDF
13. Primary cutaneous B-cell lymphoma associated with actinic prurigo.
- Author
-
Perrett CM, Harwood CA, Khorshid M, Cerio R, and McGregor JM
- Subjects
- Child, Female, Humans, Lymphoma, B-Cell pathology, Skin Neoplasms pathology, Lymphoma, B-Cell etiology, Photosensitivity Disorders complications, Prurigo complications, Skin Neoplasms etiology
- Abstract
We describe two patients with a diagnosis of actinic prurigo who subsequently developed cutaneous B-cell lymphoma. This is the first report, to our knowledge, of this association. We propose that chronic antigenic stimulation by ultraviolet radiation, in the context of actinic prurigo, may have been causal in the development of these unusual lymphomas.
- Published
- 2005
- Full Text
- View/download PDF
14. Imiquimod cream 5% for recalcitrant cutaneous warts in immunosuppressed individuals.
- Author
-
Harwood CA, Perrett CM, Brown VL, Leigh IM, McGregor JM, and Proby CM
- Subjects
- Administration, Cutaneous, Adolescent, Adult, Aminoquinolines adverse effects, Antiviral Agents adverse effects, Female, Follow-Up Studies, Foot Dermatoses drug therapy, Foot Dermatoses pathology, Foot Dermatoses virology, Hand Dermatoses drug therapy, Hand Dermatoses pathology, Hand Dermatoses virology, Humans, Imiquimod, Interferon Inducers adverse effects, Kidney Transplantation immunology, Liver Transplantation immunology, Male, Middle Aged, Prospective Studies, Recurrence, Self Administration, Treatment Outcome, Warts immunology, Warts pathology, Aminoquinolines therapeutic use, Antiviral Agents therapeutic use, Immunocompromised Host, Interferon Inducers therapeutic use, Warts drug therapy
- Abstract
Background: Viral warts may cause significant morbidity in individuals unable to mount an adequate T-helper 1 cell-mediated immune response to human papillomavirus. Imiquimod is a potent inducer of antiviral cytokine activity which has shown significant efficacy in the treatment of genital warts. Similar efficacy in cutaneous warts is not yet established., Objectives: To assess the response of persistent cutaneous warts to 5% imiquimod cream in immunosuppressed individuals., Methods: Fifteen immunosuppressed patients with warts on the hands and/or feet present for more than 18 months, which had failed to respond to a minimum of 12 weeks of topical salicylic acid and four cycles of cryotherapy, were recruited. Imiquimod 5% cream was applied in an open label, right vs. left comparison study for 24 weeks (three times weekly for 8 weeks, daily for 8 weeks, then daily with occlusion for 8 weeks)., Results: Twelve (80%) patients completed the study protocol. Benefit was seen in five patients [36% in the intent-to-treat analysis (14 patients)], including more than 30% clearance of warts in three patients and reduction in overall size of warts in two further cases. Local skin reactions occurred in four (29%) patients and were usually mild. A transient rise in creatinine (11-29% above baseline) was measured in three renal transplant recipients, but we did not consider that this was related to imiquimod exposure., Conclusions: This is the first controlled study to assess therapeutic efficacy of topical 5% imiquimod cream in persistent warts associated with immunosuppression. It provides preliminary evidence that topical imiquimod may benefit a subgroup of immunosuppressed patients with recalcitrant cutaneous warts.
- Published
- 2005
- Full Text
- View/download PDF
15. Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome.
- Author
-
Oyawoye O, Abdel Gadir A, Garner A, Constantinovici N, Perrett C, and Hardiman P
- Subjects
- Biochemistry methods, Embryo Transfer, Embryo, Mammalian physiology, Female, Fertilization, Humans, Oocytes physiology, Time Factors, Tissue Survival, Treatment Outcome, Antioxidants metabolism, Fertilization in Vitro, Follicular Fluid metabolism, Reactive Oxygen Species metabolism
- Abstract
Background: The role of free radicals and reactive oxygen species (ROS) in female reproductive function is still unclear. The present study was designed to investigate their relationship with ovulation, fertilization and conception., Methods: Follicular aspirates obtained from women undergoing IVF following controlled ovarian stimulation were evaluated using the ferric reducing antioxidant power (FRAP) assay for baseline total antioxidant capacity (TAC). Both the baseline TAC and the decline in TAC over 72 h (two-point assay) were used as markers of oxygen radical activity., Results: A total of 303 follicular aspirates from 63 women were analysed. Two hundred and eighteen (71.9%) yielded oocytes, 169 (77.5%) of these fertilized and 134 (79.3%) of these embryos survived until the time of embryo transfer. Baseline TAC was no different in follicular fluid whether the follicle contained an oocyte or not, but was significantly higher in fluid from follicles whose oocyte successfully fertilized and significantly lower in fluid from follicles where the resultant embryo survived to transfer. The decline in TAC was lower when the oocytes fertilized and higher in association with embryo viability, but the differences were not statistically significant., Conclusions: These results provide further evidence that ROS play a role in female reproductive function.
- Published
- 2003
- Full Text
- View/download PDF
16. Etanercept-induced systemic lupus erythematosus.
- Author
-
Swale VJ, Perrett CM, Denton CP, Black CM, and Rustin MH
- Subjects
- Arthritis, Rheumatoid drug therapy, Etanercept, Female, Humans, Middle Aged, Receptors, Tumor Necrosis Factor, Treatment Outcome, Antirheumatic Agents adverse effects, Immunoglobulin G adverse effects, Lupus Erythematosus, Systemic chemically induced
- Abstract
Tumour necrosis factor (TNF) is a pro-inflammatory cytokine with a role in the pathogenesis of a number of conditions including rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease. Etanercept (Enbrel; Immunex Corp., Seattle, WA, USA) is a recombinant soluble fusion protein of TNF-alpha type II receptor and IgG which acts by blocking the action of TNF-alpha. It is licensed for use in rheumatoid arthritis and juvenile chronic arthritis. A number of studies report the development of antinuclear and anti-double-stranded DNA antibodies in patients treated with TNF antagonists for rheumatoid arthritis. There are few reports of the development of clinical features of discoid, subacute or systemic lupus erythematosus. We present one of the first reported cases of etenercept-induced systemic lupus erythematosus and review the literature of lupus and TNF antagonists.
- Published
- 2003
- Full Text
- View/download PDF
17. Gravitational erythema.
- Author
-
Perrett CM, Berth-Jones J, and Dharma B
- Subjects
- Adult, Arm, Gravitation, Humans, Leg Dermatoses etiology, Male, Posture, Erythema etiology
- Published
- 2003
- Full Text
- View/download PDF
18. Tea tree oil dermatitis associated with linear IgA disease.
- Author
-
Perrett CM, Evans AV, and Russell-Jones R
- Subjects
- Adolescent, Female, Humans, Anti-Infective Agents, Local adverse effects, Drug Eruptions etiology, Skin Diseases, Vesiculobullous chemically induced, Tea Tree Oil adverse effects
- Abstract
Tea tree oil dermatitis is an increasingly common finding, reflecting the strong demand for natural remedies and aromatic substances. Linear immunoglobulin A (IgA) disease is a rare acquired subepidermal blistering disorder, characterized by basement membrane zone IgA deposition. We describe a patient in whom linear IgA disease appears to have been precipitated by a contact reaction to tea tree oil.
- Published
- 2003
- Full Text
- View/download PDF
19. The effect of topical corticosteroids on Ki67 and p53 expression in vulval lichen sclerosus.
- Author
-
Rolfe KJ, Crow JC, Reid WM, Benjamin E, MacLean AB, and Perrett CW
- Subjects
- Administration, Topical, Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Glucocorticoids, Humans, Immunoenzyme Techniques, Ki-67 Antigen metabolism, Lichen Sclerosus et Atrophicus metabolism, Middle Aged, Tumor Suppressor Protein p53 metabolism, Vulva metabolism, Vulvar Diseases metabolism, Anti-Inflammatory Agents pharmacology, Ki-67 Antigen drug effects, Lichen Sclerosus et Atrophicus drug therapy, Tumor Suppressor Protein p53 drug effects, Vulvar Diseases drug therapy
- Abstract
Background: Topical corticosteroids have become the treatment of choice for genital lichen sclerosus (LS) and are believed to be required for long-term relief of symptoms., Objective: To compare vulval LS that had been treated with topical corticosteroids, vulval LS that had not received topical corticosteroids, and histologically normal vulval skin., Methods: We used immunohistochemistry to look for Ki67 expression and abnormal p53 expression., Results: We found a statistically significant difference for p53 overexpression, with increased levels seen when comparing corticosteroid-treated LS with normal genital skin (P = 0.011). Ki67 expression was also significantly higher in the corticosteroid-treated group compared with normal genital skin (P = 0.001), and increased levels were also found in the treated group compared with untreated LS (P = 0.05)., Conclusions: Our data suggest that topical corticosteroids have an effect on cell cycle proteins in genital skin and, in particular, genital skin with LS changes.
- Published
- 2002
- Full Text
- View/download PDF
20. Allelic deletion in pituitary adenomas reflects aggressive biological activity and has potential value as a prognostic marker.
- Author
-
Bates AS, Farrell WE, Bicknell EJ, McNicol AM, Talbot AJ, Broome JC, Perrett CW, Thakker RV, and Clayton RN
- Subjects
- Adolescent, Adult, Aged, Biomarkers, Chromosome Mapping, Female, Heterozygote, Humans, Immunohistochemistry, Male, Middle Aged, Neoplasm Invasiveness, Prognosis, Adenoma genetics, Adenoma pathology, Alleles, Gene Deletion, Pituitary Neoplasms genetics, Pituitary Neoplasms pathology
- Abstract
Tumors of the pituitary gland are usually benign adenomas and account for 10% of all intracranial neoplasms. Five pituitary tumors have previously been reported to harbor multiple allelic deletions. Of these, three displayed particularly aggressive biological behavior, whereas there were no clinical details provided for the others. This study was designed to test the hypothesis that genetic deletions are a marker of invasive behavior and to identify the loci most commonly involved. Accordingly, we studied two cohorts of pituitary tumors, classified radiologically as invasive or noninvasive, for loss of heterozygosity (LOH). There is a significantly higher frequency of LOH in invasive tumors (10.8% of all loci examined) compared to noninvasive tumors (2.4%; P < 0.001). Of the 11 loci investigated, 75% of the allelic deletions identified in invasive tumors were found at 4 loci: 11q13, 13q12-14, 10q, and 1p. Twenty of 47 invasive tumors had evidence of at least 1 allelic deletion, whereas 14 of 20 had more than 1. Of the 6 tumors with only 1 deletion, 5 involved the 11q13 locus, suggesting that this is an early change in the transition from noninvasive to invasive adenoma. Comparison of invasive and noninvasive tumors demonstrates a significantly higher frequency of deletions affecting 11q13 (P < 0.001), 13q12-14 (P < 0.05), and 10q26 (P < 0.05) in invasive tumors. In addition, allelic deletion correlates with increasingly invasive behavior (modified Hardy classification), as 73% of grade 4 tumors compared to 33% of grade 3 and 9.5% of grade 1 and 2 tumors demonstrated LOH at any locus. Furthermore, in some tumors we identified a breakpoint between markers intragenic and extragenic to the retinoblastoma gene (Rb1) on chromosome 13q, suggesting that tumor suppressor genes other than or in addition to Rb1 may be involved in pituitary tumorigenesis. This was further supported by the presence of Rb protein in two of four tumors where the genetic loss extended to include the intragenic marker D13S153. Early identification of tumors with likely invasive potential by means of genetic analysis (LOH) may provide useful information on potential tumor behavior and aid tumor management in a manner that is not possible using routine histological methods. A large prospective study is required in patients without radiological evidence of invasion to assess the value of LOH in predicting outcome and for planning treatment.
- Published
- 1997
- Full Text
- View/download PDF
21. P53 protein accumulates in Cushings adenomas and invasive non-functional adenomas.
- Author
-
Buckley N, Bates AS, Broome JC, Strange RC, Perrett CW, Burke CW, and Clayton RN
- Subjects
- Adenoma chemistry, Adenoma etiology, Adenoma, Basophil chemistry, Adenoma, Basophil etiology, Adrenocorticotropic Hormone metabolism, Humans, Immunohistochemistry, Mutation, Pituitary Neoplasms chemistry, Pituitary Neoplasms etiology, Tumor Suppressor Protein p53 analysis, Adenoma metabolism, Adenoma, Basophil metabolism, Pituitary Neoplasms metabolism, Tumor Suppressor Protein p53 metabolism
- Abstract
The p53 protein, a negative regulator of cell growth, plays an important role in the pathogenesis of many human tumours following gene mutation and/or deletion. We screened a large number of sporadic pituitary tumours for p53 protein accumulation suggestive of gene mutation. Samples were divided into benign adenomas (n = 95) and invasive tumours with local or distant invasion (n = 26). All main tumour classes were represented. Putative p53 mutations were detected by immunohistochemistry on paraffin-embedded sections using polyclonal CM-1 and monoclonal DO-7 and PAb1801 antibodies. Results were compared to normal post-mortem pituitary tissue controls (n = 17). p53 protein accumulation was detected in invasive tumours (16%), but only in corticotrophinomas (2/4) and non-functional tumours (4/15). In non-invasive adenomas, protein accumulation was observed only in ACTH-secreting tumours where 50% were positive (16/32). No protein accumulation was identified in any control tissue. These results indicate that p53 protein accumulation may play a role in the development of Cushings adenomas and in the progression of non-functional tumours to the invasive state.
- Published
- 1995
- Full Text
- View/download PDF
22. p53 Protein accumulates in Cushings adenomas and invasive non-functional adenomas.
- Author
-
Buckley N, Bates AS, Broome JC, Strange RC, Perrett CW, Burke CW, and Clayton RN
- Subjects
- Adenoma chemistry, Adenoma etiology, Adenoma, Basophil chemistry, Adenoma, Basophil etiology, Adrenocorticotropic Hormone metabolism, Humans, Immunohistochemistry, Mutation, Pituitary Neoplasms chemistry, Pituitary Neoplasms etiology, Tumor Suppressor Protein p53 analysis, Adenoma metabolism, Adenoma, Basophil metabolism, Pituitary Neoplasms metabolism, Tumor Suppressor Protein p53 metabolism
- Abstract
The p53 protein, a negative regulator of cell growth, plays an important role in the pathogenesis of many human tumours following gene mutation and/or deletion. We screened a large number of sporadic pituitary tumours for p53 protein accumulation suggestive of gene mutation. Samples were divided into benign adenomas (n = 95) and invasive tumours with local or distant invasion (n = 26). All main tumour classes were represented. Putative p53 mutations were detected by immunohistochemistry on paraffin-embedded sections using polyclonal CM-1 and monoclonal DO-7 and PAb1801 antibodies. Results were compared to normal post-mortem pituitary tissue controls (n = 17). p53 protein accumulation was detected in invasive tumours (16%), but only in corticotrophinomas (2/4) and non-functional tumours (4/15). In non-invasive adenomas, protein accumulation was observed only in ACTH-secreting tumours where 50% were positive (16/32). No protein accumulation was identified in any control tissue. These results indicate that p53 protein accumulation may play a role in the development of Cushings adenomas and in the progression of non-functional tumours to the invasive state.
- Published
- 1994
- Full Text
- View/download PDF
23. Molecular genetic studies of sporadic pituitary tumors.
- Author
-
Boggild MD, Jenkinson S, Pistorello M, Boscaro M, Scanarini M, McTernan P, Perrett CW, Thakker RV, and Clayton RN
- Subjects
- Adenoma pathology, Alleles, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 7, DNA, Neoplasm genetics, Exons, Gene Deletion, Gene Expression Regulation, Neoplastic genetics, Gene Rearrangement genetics, Genes, Suppressor genetics, Heterozygote, Humans, Immunohistochemistry, Mutation genetics, Oncogenes genetics, Pituitary Neoplasms pathology, Polymerase Chain Reaction, Adenoma genetics, Pituitary Neoplasms genetics
- Abstract
Tumor formation may result from the activation of dominant oncogenes or by inactivation of recessive, tumor suppressor genes. The role of such mutations in the development of pituitary tumors has been studied. Tumors from 88 patients, representing the 4 major classes of adenoma, were investigated. In DNA extracted from matched leukocyte and tumor samples, allelic deletions were sought with 15 probes identifying restriction fragment length polymorphisms on chromosomes 1, 5, 10, 11, 13, 17, 20, and 22. Evidence of amplification or rearrangement of 10 recognized cellular oncogenes (N-ras, mycL1, mycN, myc, H-ras, bcl1, H-stf1, sea, kraS2, and fos) was sought in tumor DNA. Activating dominant mutations of Gs alpha were detected using the polymerase chain reaction to amplify exons 7-10 and hybridizing the product to normal and mutant allele-specific oligonucleotides. Allelic deletions on chromosome 11 were identified in 16 tumors (18%) representing all 4 major subtypes. Deletions on other autosomes were observed in less than 6% of tumors. Three adenomas had deletions on multiple autosomes, 2 of these were aggressive and recurrent. Mutations of Gs alpha were confirmed to be specific to somatotrophinomas, being identified in 36% of such tumors in this series. No evidence of amplification or rearrangement of other recognized cellular oncogenes was found. Inactivation of a recessive oncogene on chromosome 11 is an important and possibly early event in the development of the four major types of pituitary adenoma, whereas activating mutations of Gs alpha are confirmed to be specific to somatotropinomas. Two aggressive tumors were found to have multiple autosomal losses, suggesting a multistep progression in the development of tumors of this phenotype.
- Published
- 1994
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.