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ABSTRACT: Tumour hypoxia is associated with over 70% of solid tumours including prostate and colorectal cancer. Hypoxia promotes tumour progression and resistance to treatment. Carbonic anhydrase IX (CA IX) is an endogenous marker of hypoxia. It is expressed in lung and renal cell carcinomas and is associated with a poor prognosis. CA IX has an important role in maintaining pH levels in the highly metabolically active cancer cell. The expression of CA IX in prostate cancer has not previously been investigated. Immunohistochemistry was used to examine CA IX expression in 59 patients, using tissue microarrays (TMAs) and full sections of BPH, surrounding stroma and prostate adenocarcinoma. Cores reviewed included 189 BPH, 130 Gleason grade 3, 93 Gleason grade 4, 40 Gleason grade 5. CA IX expression in colorectal cancer and HIF 1alpha in prostate cancer acted as positive controls. There was only occasional cell staining for CA IX expression. Although prostate cancer is a hypoxic tumour it does not express CA IX. This implies it relies on alternative pathways for maintaining pH balance in cancer. These studies would indicate that CA IX is not a suitable marker of hypoxia in prostate cancer.
Prostate cancer and prostatic diseases 06/2010; 13(2):178-81. · 2.10 Impact Factor
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Ruth Foley,
Laure Marignol,
Arun Z Thomas,
Ivor M Cullen,
Antoinette S Perry,
Prerna Tewari,
Anthony O'Grady, Elaine Kay,
Barbara Dunne,
Barbara Loftus,
William R Watson,
John M Fitzpatrick,
Karen Woodson,
Terri Lehman,
Donal Hollywood,
Thomas H Lynch,
Mark Lawler
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ABSTRACT: We investigated the role of the C1772T polymorphisms in exon 12 of the Hypoxia-inducible factor-1 alpha (HIF-1alpha) gene C1772T genotype in prostate cancer (PCa) and amplification of the hypoxic response. We identified the heterozygous germline CT genotype as an increased risk factor for clinically localised prostate cancer (Odds ratio = 6.2; p < 0.0001). While immunostaining intensity for HIF-1alpha and VEGF was significantly enhanced in 75% of PCa specimens when compared to matched benign specimens (p < 0.0001), the CT genotype did not modulate the kinetics of HIF-1alpha protein expression in hypoxia in vitro, and was not associated with enhanced expression of hypoxic biomarkers. This study provides the first evidence of an increased risk for clinically localised prostate cancer in men carrying the C1772T HIF-1alpha gene polymorphism. Although our results did not suggest an association between expression of hypoxic biomarkers and genotype status, the correlation may merit further investigation.
Cancer biology & therapy 02/2009; 8(2):118-24. · 2.64 Impact Factor
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ABSTRACT: Audit is an essential requirement of a cervical screening programme to ensure that laboratories are practising to agreed standards, and to ensure high quality patient care. The aim of this study was to assess the ability to audit high-grade cytology smear reports in a large cervical cytology laboratory in Ireland, where a nationally organised screening programme does not exist. Seven hundred and five questionnaires were forwarded to smear takers requesting follow-up data regarding high grade smear results from 2003. Seventy-four percent of the questionnaires were returned containing insufficient data, with a "don't know result" rate of >50%. This attempt at detailed audit took place 5 years ago. Annual internal audit continues to the best of the laboratory's ability but the situation, in terms of a centralised database in the context of a national screening programme, remains unchanged. A National Cervical Cytology Screening Programme is essential to centralise patient data, to allow for improved patient care, patient follow-up and audit.
Irish medical journal 07/2008; 101(6):175-7.
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ABSTRACT: To investigate the expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer (NMSC) and to compare their expression between different tumour types and with clinicopathological factors.
A study of 11 normal skin, 29 Bowen's disease (BD), 40 squamous cell carcinoma (SCC) and 38 basal cell carcinoma (BCC) samples for MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was carried out using immunohistochemistry and in situ hybridization. The expression of all metalloproteinases was greater in tumours than in normal skin. MMP-2 and MMP-9 expression was more extensive in the stroma of SCC than of BCC or BD. TIMP-1 expression was greater in the stroma of BCC than of SCC or BD and TIMP-2 expression was greater in the stroma of SCC than of BD. There was a correlation between increased metalloproteinase expression and depth of lesion (MMP-2 and TIMP-2), inflammation (MMP-2, MMP-9, TIMP-1 and TIMP-2) and microvessel density (MMP-2, MMP-9 and TIMP-2).
MMP-2, MMP-9, TIMP-1 and TIMP-2 play an important role in the pathogenesis of non-melanoma skin cancer, but differ significantly in their expression levels between the tumour types examined. The immunoexpression of these proteins may be useful indicators of cutaneous cancer invasion and progression.
Histopathology 01/2008; 51(6):793-804. · 3.08 Impact Factor
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ABSTRACT: Cervical cancer is the second most common cancer amongst women worldwide. It is now accepted that almost all cervical cancers arise through the disruption of the pathways of p53 and the product of the retinoblastoma gene (pRb) by high-risk Human Papilloma Virus (HPV) oncoproteins E6 and E7. In cervical cancer p16INK4a is strongly over expressed when pRb is inactivated by HPV E7. This over expression highlights the potential of p16INK4a as a marker for cervical intraepithelial neoplasia and cervical cancer. Immunocytochemical (ICC) analysis of P16INK4a expression was performed on 30 negative, 30 Borderline, 30 CIN1 and 30 High Grade ThinPrep® cervical samples selected from 1094 consented samples received for routine cervical screening assessment. The results were correlated with HR-HPV status as determined by a PCR assay and the cytology findings. In addition a real time RT-PCR technique was employed to evaluate P16INK4a gene expression in 50 of the 120 study samples. Eighty-five of the 120 cervical samples were found positive by the ICC assay, 13/30 Negative, 23/30 Borderline, 20/30 CIN 1 and 29/30 High Grade. The ICC staining results were supported by the results of the P16INK4a real time RT-PCR analysis and the HR-HPV PCR assay. Interestingly not all HR-HPV positive samples were P16INK4a ICC positive, suggesting the marker may be capable of discriminating between productive viral infections and active cell transformation. In conclusion P16INK4a is a useful marker of HR-HPV mediated cervical dyskaryosis in ThinPrep® samples and may be utilized as an adjunct to the Pap smear to aid in the identification of patients with lesions which are more likely to progress to cervical cancer. Additional studies correlating p16INK4a ICC with viral load, viral integration and E6/E7 expression are required to establish how discriminatory a marker p16INK4a truly is.
Cytopathology 08/2006; 17(s1):28 - 28. · 1.59 Impact Factor
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ABSTRACT: Papillomaviruses are the causative agents of the common wart. Although the human papillomavirus is strongly associated with certain dysplastic and malignant lesions, its exact role in tumour development remains to be determined. This review examines the role of human papilloma virus as a potential oncogenic agent in human mucosal and non-mucosal squamous cell carcinoma.
Journal of the European Academy of Dermatology and Venereology 07/2006; 9(2):103 - 110. · 2.98 Impact Factor
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ABSTRACT: The incidence of distal (corpus and antrum) gastric adenocarcinoma is decreasing with a simultaneous increase in incidence of proximal (cardia) adenocarcinoma. Epidemiological studies suggest that they may represent different diseases but corroborative molecular data are scarce. Intestinal metaplasia may have a lower malignant potential in the proximal stomach but regardless of the locations, its specificity as a predictor of carcinoma is low.
The aim of this study was to establish whether human telomerase reverse transcriptase expression differs at various points in proximal versus distal gastric carcinogenesis and to test the utility of human telomerase reverse transcriptase expression as a marker of cancer risk in intestinal metaplasia.
Wax-embedded tissue from proximal and distal stomach including normal mucosa (n=86), intestinal metaplasia (n=83) and carcinoma (n=101) were used and slides were immunostained for human telomerase reverse transcriptase and pRb and scored semi-quantitatively.
The results showed that in both proximal and distal stomach, human telomerase reverse transcriptase expression rates increased from normal mucosa to cancer. High rates of human telomerase reverse transcriptase expression were seen in the proliferative zones of glands in intestinal metaplasia. In both the locations, loss of pRb expression correlated with higher human telomerase reverse transcriptase expression.
In conclusion, telomerase activity appears to be an early event in both proximal and distal gastric carcinogenesis and human telomerase reverse transcriptase is expressed in intestinal metaplasia. Telomerase re-expression may be facilitated by pRb inactivation.
Digestive and Liver Disease 07/2005; 37(6):439-45. · 3.05 Impact Factor
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ABSTRACT: To assess the practicality of using a miniature tissue microarray (TMA) with several examples of each HercepTest score from 0 to 3+ as a control for routine HercepTest immunohistochemistry.
A TMA was constructed from in house cases of breast cancer where HercepTest on the whole sections showed scores 0, 1+, 2+, or 3+. The TMA, which measured 5 x 5 mm, was designed with four rows (each representing scores 0, 1+, 2+, and 3+), with five 0.6 mm cores from separate cases. In all, 20 individual cases were represented and the TMA took less than one hour to construct. Fifty sequential 4 microm sections were cut from the TMA to maximise the number of available sections. They were stored at 4 degrees C for 1-270 days and when a case needed HercepTest staining the section was added to the TMA tissue control slide.
All slides contained tissue spots and immunohistochemical staining was consistent throughout the time period.
The miniature TMA with examples of all HercepTest scores described here is an ideal tissue control and can be used as a visual reference for scoring a case. Slides stored at 4 degrees C could be used for up to 270 days.
Journal of Clinical Pathology 12/2004; 57(11):1229-31. · 2.31 Impact Factor
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ABSTRACT: To evaluate the use of tissue microarray (TMA) technology as a validation tool for HER2 testing by both immunocytochemistry (ICC) and fluorescence in situ hybridisation (FISH) in the diagnostic setting.
TMA constructs from 57 cases of breast cancer were evaluated for HER2 (by ICC and FISH) by two centres. The results were compared.
There was a high level of concordance for both ICC and FISH. In five "discrepant" cases only three would have had a potential impact on patient management.
Validation of HER2 analysis in the clinical setting by ICC and FISH is essential. The use of TMAs provides for an economy of scale and would be practical in the setting of interlaboratory and intralaboratory validation. It is suggested that routine HER2 ICC and FISH should continue to be performed in laboratories on whole sections. Following this, TMAs would be constructed for all cases of breast cancer. ICC and FISH would be performed on these to validate the results. The TMAs would be available for circulation to other centres for validation purposes. The standardisation of testing between centres, the potential difficulty of minimum case numbers, and the workload issues surrounding validation would all be facilitated by this approach.
Journal of Clinical Pathology 12/2004; 57(11):1140-4. · 2.31 Impact Factor
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ABSTRACT: Borderline nuclear changes (BNC) account for 5-20% of cervical smears, and their outcome is unpredictable. Current management involves repeat smears at 6-mo intervals, for a further 12 mo with referral for colposcopy, if the changes persist. Given the uncertainty surrounding the natural history of BNC and the claim that many patients are further investigated unnecessarily and potentially "overtreated," the aim of this study was to determine the outcome for patients with a diagnosis of BNC to define whether the management protocol is appropriate for this patient group in our laboratory. A total of 808 patients with BNC were followed up. There was a 4.05% progression to high-grade dyskaryosis, and most of these were detected within the first year of follow-up. This at least justifies the early and intense follow-up of this patient group until a reliable "triage tool" is adopted to pre-select those patients with BNC who will progress or revert to negative.
Diagnostic Cytopathology 12/2003; 29(5):267-9. · 1.16 Impact Factor
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ABSTRACT: The current study examined cytokeratin (CK)7 and 20 as well as MUC1-6 immunoprofiles in oesophageal, gastric and gastro-oesophageal junction (GOJ) adenocarcinomas. The aim was to compare expression patterns in these locations as aids to accurate classification of these morphologically similar carcinomas which all may involve the GOJ.
Tissue microarrays were constructed using tissue from 14 oesophageal, 78 gastric and 39 GOJ adenocarcinomas. Sections were immunostained with CK7, CK20, MUC1, MUC2, MUC5AC and MUC6. The results of this study showed no differences in CK7 and CK20 expression patterns in the three locations. MUC2 expression was higher proximally (43% of oesophageal, 28% of GOJ and 17% of gastric carcinomas) and MUC6 expression was higher distally (7% of oesophageal, 28% of GOJ and 15% of gastric carcinomas). MUC1 expression was associated with higher pTNM-stage.
CK 7/20 profiles have no role in distinguishing tumours of the three locations. Mucin expression patterns differed in oesophageal and gastric adenocarcinomas, although not sufficiently to classify individual cases. GOJ adenocarcinomas showed a mucin expression pattern that was partly 'gastric', and partly 'oesophageal'. MUC1 expression was associated with a higher pTNM stage.
Histopathology 12/2003; 43(5):453-61. · 3.08 Impact Factor
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ABSTRACT: Antiangiogenic therapy has the potential to moderate tumour and micrometastatic growth. Its use in the perioperative period is attractive but its potential to compromise wound and anastomotic healing is a cause for concern. Tamoxifen is antiangiogenic but also favourably modifies some aspects of wound healing. We hypothesised that tamoxifen would not adversely affect skin wound and gut anastomotic healing.
A previously established model of tamoxifen, administered orally at antiangiogenic doses (20 mg/ml arachais oil/day), was used. Animals received two days pretreatment prior to laparotomy and small bowel anastomosis. Treatment was continued until completion of the study. The principal outcome measures are survival, macroscopic wound and anastomotic healing, anastomotic bursting pressure and PVA sponge granuloma hydroxyproline (OHP) content.
Tamoxifen treated animals had fewer complications of skin wound healing than controls (4.5% vs. 19.5%; chi(2) 4.65, 1 d.f., P < 0.05). There was no significant difference in adhesion formation or macroscopic complications of anastomotic healing. Anastomotic bursting pressure was greater in tamoxifen treated animals at postoperative day 3 (39 +/- 4.4 vs. 22.5 +/- 3.5 mmHg; P < 0.01) and equal to that of controls on postoperative day 5 (144.4 +/- 9.4 vs. 127.3 +/- 10.9 mmHg; P = ns). Tamoxifen treated animals weighed significantly less than placebo controls from postoperative day 3 with no difference in mortality between groups (chi(2) = 0.06, 1 d.f., P = ns). PVA sponge granuloma OHP content on day 7 was higher in tamoxifen-treated animals (2.93 +/- 0.4 vs. 1.4 +/- 0.4 mg OHP/mg dry sponge weight; P = 0.03).
Antiangiogenic therapy with tamoxifen has no demonstrable adverse effects on wound or anastomotic repair and its perioperative use is compatible with successful early surgical outcomes.
Colorectal Disease 07/2003; 5(4):335-41. · 2.93 Impact Factor
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ABSTRACT: Tissue microarrays offer an efficient way of examining a large number of tumour cases on a single glass slide. A major concern, however, is tumour heterogeneity. Also, the use of tissue microarrays in biopsy material is unexplored. The purpose of the present study was to assess the possibility and validity of arraying three 0.6-mm cores per case in endoscopic gastric cancer biopsies for immunophenotyping.
Thirty-eight cases were studied with immunohistochemical staining for p53, CD44v6 and vascular endothelial growth factor. Full tissue sections were compared with triple core-tissue microarrays. Thirty-six cases contained three cores with tumour, one case contained two cores with tumour and one case contained only a single core with viable tumour and was excluded. Three further cores had been lost from three separate cases on the sections for immunohistochemistry. kappa values for whole-sections versus tissue microarrays ranged between 0.77 and 0.94. p53 immunohistochemical staining (interpretation as + or -) yielded the best result with only 1/37 mismatches, whereas CD44v6 (graded both for intensity and extent) showed 3/37 mismatches. The small depth of tissue in cores from biopsies necessitates all cores being arrayed flush with the face of the recipient wax block for maximizing the number of sections available. Compared with the first section over 30 additional 4- micro m sections were available before the first case (with one core left) had to be excluded and 80 sections before half the tissue cores were lost.
It is impracticable to array more than 120-150 cores per block. Tissue microarray with three cores per case is feasible and valid for studying biopsy material.
Histopathology 02/2003; 42(1):70-6. · 3.08 Impact Factor
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ABSTRACT: intimal hyperplasia (IH) is a major cause of re-stenosis post-vascular intervention. Induction of heat shock proteins (HSPs), by thermal pre-conditioning, reduces IH. Our aim was to investigate the effect of the pharmacological HSP inducer herbimycin A on IH in the rat carotid balloon injury model. Materials and Methods: thirty male Sprague-Dawley rats were randomized into three groups. All groups underwent balloon injury to the left carotid artery. Stress proteins were induced 18 h pre-operatively by heat shock or herbimycin A. Two weeks post-operatively, animals were sacrificed and carotid intima/media area ratio (I/M ratio) calculated using computerized planimetry. Neo-intimal proliferation was assessed immunohistochemically with PCNA (proliferating cell nuclear antigen). Western blot and immunohistochemistry for arterial HSP70 and HSP27 were performed.
heat stress and herbimycin significantly reduced the I/M ratio (p < 0.05 vs balloon injury alone). Neo-intimal proliferation was significantly reduced in the heat stress and herbimycin groups (p < 0.05 vs balloon injury alone). Heat stress induced arterial HSP70 and HSP27. Herbimycin A increased arterial HSP27.
herbimycin A significantly attenuates IH after balloon injury. HSP27 may be the HSP involved in mediating this response. Pharmacological inducers of HSPs may have a therapeutic role to play in preventing re-stenosis post-vascular intervention.
European Journal of Vascular and Endovascular Surgery 01/2003; 25(1):40-7. · 2.99 Impact Factor
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M Murphy,
M J E M F Mabruk,
P Lenane,
A Liew,
P McCann,
A Buckley,
C O Flatharta,
D Hevey,
P Billet,
W Robertson,
S Javed,
M Leader, E Kay,
G M Murphy
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ABSTRACT: Ultraviolet light (UV) is known to cause DNA damage in the epidermis. The damaged DNA is repaired or deleted by apoptosis to prevent the generation of cancer. It has been suggested that a deficient apoptotic mechanism may predispose individuals to skin cancer. Therefore, the response of normal controls and patients with basal cell carcinoma (BCC) to UV irradiation was investigated.
The buttock skin from normal volunteers and patients with BCC was irradiated using solar simulated radiation (SSR). SSR mimics the effect of natural sunlight. Skin biopsies were excised and examined for p53, p21, and Bax protein expression and for the induction of apoptosis.
At 33 hours after UV irradiation, the induction of apoptosis was significantly higher (p = 0.04) in patients with BCC than in normal volunteers (Mann Whitney test). A trend towards higher p21 expression was found at 33 hours in patients with BCC (mean, 18.69 positive cells/field) than in normal volunteers (mean, 9.89), although this difference was not significant (p = 0.05 positive cells/field).
These results may imply that patients with BCC have enhanced sensitivity to UV irradiation or that there is some defect in the cell arrest or repair pathways, which results in damaged cells been pushed into apoptosis rather than repair.
Journal of Clinical Pathology 12/2002; 55(11):829-33. · 2.31 Impact Factor
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ABSTRACT: Gastric carcinoma is one of the most common malignancies worldwide, particularly in Japan and China. Inactivation of the adenomatous polyposis coli ( ) gene, a tumor suppressor gene, has been shown to play a significant role in the development of colorectal carcinoma, and it has been suggested that it may play a role throughout the digestive tract, including the stomach. This study assesses gene expression in normal gastric mucosa and gastric adenocarcinoma using an antibody to the C-terminal region. One hundred twenty cases of gastric adenocarcinoma were examined from the files of Beaumont Hospital, Dublin, Ireland, and China Medical University, Shenyang, China. Ninety-one cases were informative. Of these, 78% revealed loss of staining. Loss of staining in adenocarcinoma showed no association with tumor type, tumor, stage or patient nationality. Loss of staining was also found in nine of 35 cases (26%) of intestinal metaplasia. In conclusion, loss of the gene, as determined by immunohistochemical staining, appears to be an early event in gastric carcinogenesis. Immunohistochemistry is a sensitive method for detection of this loss.
Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 10/2002; 10(3):221-4. · 1.63 Impact Factor
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ABSTRACT: The conventional Papanicolaou smear is associated with variable false positive and false negative rates, difficulties with interpretation and high unsatisfactory and suboptimal rates. Newer fluid-based methods such as the ThinPrep 2000 system (Cytyc Corp., Boxborough, MA) are said to overcome these difficulties. The aim of this study was to compare the conventional smear with the ThinPrep method in a busy, routine cytology screening laboratory setting. One thousand split samples were evaluated. Using ThinPrep, the results showed an increased sensitivity and a dramatic improvement in specimen adequacy, with a combined 17.2% reduction in 'unsatisfactory' and 'suboptimal' reports. Screening time per slide was also reduced to 3-4 min. In conclusion, we report an increase in sensitivity, a reduction in screening time and a dramatic improvement in specimen adequacy with the ThinPrep method.
Cytopathology 09/2002; 13(4):200-5. · 1.59 Impact Factor
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ABSTRACT: Oral lichen planus (OLP) is a chronic inflammatory condition. Clinically, it is characterised by the presence of a white lace-like lesion on the buccal mucosa, tongue, and gingivae, with erosions and ulceration. The World Health Organisation considers OLP to be a premalignant condition.
To investigate expression of the telomerase RNA component (hTR) in OLP compared with normal control buccal mucosa and to assess the possibility of using hTR expression as a marker for malignant transformation in OLP.
hTR expression was analysed in 40 cases of OLP and 18 normal control buccal mucosa samples using an RNA in situ hybridisation approach.
Strong hTR RNA expression was seen in the basal, suprabasal, and to a lesser extent in the upper epithelial layers in 36 of the 40 OLP lesions examined. Infiltrating subepithelial lymphocytes in OLP were also shown to express hTR RNA. Weak hTR RNA expression was seen in seven of the 18 normal control buccal mucosa specimens, with expression confined exclusively to the basal layer of the epithelium and absent in the suprabasal and upper layers.
The telomerase RNA component hTR is found to be highly expressed in the epithelium of non-dysplastic OLP lesions. It is possible that this high expression is related to the increased cellular proliferation seen in OLP lesions rather than being an indicator of susceptibility to malignancy. Thus, hTR RNA expression may not be a suitable marker for predicting malignant transformation in OLP.
Journal of Clinical Pathology 09/2002; 55(8):602-7. · 2.31 Impact Factor
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ABSTRACT: The effect of selective and non-selective cyclo-oxygenase inhibition on tumour growth and metastasis in an orthotopic model of breast cancer was investigated. 4T1 mammary adenocarcinoma cells were injected into the mammary fat pad of female BALB/c mice. When tumours reached a mean tumour diameter of 8.4+/-0.4 mm, mice were randomised into three groups (n=6 per group) and received daily intraperitoneal injections of the selective cyclo-oxygenase-2 inhibitor, SC-236, the non selective cyclo-oxygenase inhibitor, Indomethacin, or drug vehicle. Tumour diameter was recorded on alternate days. From 8 days after initiation of treatment, tumour diameter in animals treated with either SC-236 or indomethacin was significantly reduced relative to controls. Both primary tumour weight and the number of lung metastases were significantly reduced in the SC-236 and indomethacin treated mice. Microvessel density was reduced and tumor cell apoptosis increased in the primary tumour of mice treated with either the selective or non-selective cyclo-oxygenase inhibitor. In vitro, cyclo-oxygenase inhibition decreased vascular endothelial growth factor production and increased apoptosis of tumour cells. Our results suggest that cyclo-oxygenase inhibitors will be of value in the treatment of both primary and metastatic breast cancer.
British Journal of Cancer 08/2002; 87(2):231-7. · 5.04 Impact Factor
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ABSTRACT: Ultraviolet radiation (UVR) damages keratinocytes. Direct DNA damage may undergo enzymatic repair followed by resumption of the normal cell cycle. Cells may also be eliminated without inflammation by the error-free process of programmed cell death or apoptosis. Necrosis of cells can occur after overwhelming damage. Failure of apoptosis leads to retention of cells with persistent mutations.
This study investigates p53-dependent apoptotic responses in normal skin following solar-simulated radiation (SSR).
Sun-protected buttock skin from normal volunteers with no history or clinical evidence of skin cancer was exposed to graded doses of SSR, 0.5, 1, 2 and 3 times the minimal erythema dose (MED). Biopsies taken at a range of time points (4.5, 9, 24, 33, 48 and 72 h) after UVR, quantified the time course and dose-response of apoptosis and the expression of the relevant proteins, p53, p21waf1/Cip1 and Bax, by single and double labelling techniques.
Apoptosis was upregulated in a dose-dependent manner as was the expression of p53, p21waf1/Cip1 and Bax in response to SSR. Following exposure to 3 MEDs it was found that: (i) the maximum number of apoptotic cells occurred at 48 h; (ii) p53 protein expression was upregulated from 4 to 72 h preceding peak p21waf1/Cip1 protein expression (9-48 h) and peak Bax protein expression (33 h).
These results suggest that, following SSR, normal human skin induces apoptosis by the p53, p21waf1/Cip1, Bax pathway in vivo. In addition, induction of apoptosis and expression of p53, p21waf1/Cip1 and Bax occurs in a dose-dependent manner.
British Journal of Dermatology 08/2002; 147(1):110-7. · 3.67 Impact Factor
