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Biomedical subjects

E W Kay

Publications and source records attributed to E W Kay.

At least 19 recordsLinked to original sources
PubMed2003

Well differentiated fetal adenocarcinoma of the lung in a 29 year old woman.

This report describes a case of well differentiated fetal adenocarcinoma of the lung in a 29 year old female smoker. The histological pattern and immunohistochemical profile were consistent with well differentiated fetal adenocarcinoma and the patient made an uneventful postoperative recovery with no recurrence after 18 months. This neoplasm is a rare lung tumour that is composed of glycogen rich neoplastic glands and tubules that resembles fetal lung at 10 to 15 weeks of gestation. It is important to identify this rare variant of adenocarcinoma because it is a low grade malignancy with low associated mortality.

Adenocarcinoma↗
PubMed2001

Poor agreement in recognition of abnormal mitoses: requirement for standardized and robust definitions.

AIMS: The finding of abnormal mitoses is a helpful feature in differentiating between benign and malignant neoplasia and has prognostic significance for some tumours. As the use of a histopathological variable is limited by the reproducibility of its recognition, we tested the interobserver agreement in the classification of abnormal mitoses among histopathologists. METHODS adn RESULTS: Ten practising histopathologists were shown 30 potential mitotic figures and were asked to classify these as 'normal mitoses', 'abnormal mitoses' or 'not mitoses' according to the criteria each pathologist used in their routine practice. The results were analysed using kappa statistics. Overall agreement was only fair with a combined kappa of 0.31 and there was unanimous categorization of only four of 30 test items, none of which was called abnormal. The poorest result was obtained for the category 'abnormal mitosis' with only slight agreement (kappa 0.19). Agreement for the other categories varied from moderate (kappa = 0.45) for 'not a mitosis' to fair (kappa = 0.26) for 'normal mitosis'. Comparison of the results for observer pairs showed that for 12 out of the 45 possible pairings, there was no more agreement than might be expected by chance alone. CONCLUSION: Agreement is poor among practising histopathologists in the recognition of abnormal mitoses. A standardized and robust definition is needed if diagnostic and prognostic significance is accorded to the finding of an abnormal mitosis in the context of neoplasia.

Humans↗
PubMed2001

Altered p53 expression in benign and malignant skin lesions from renal transplant recipients and immunocompetent patients with skin cancer: correlation with human papillomaviruses?

Renal transplant recipients are prone to numerous benign and malignant skin lesions. Previous work in the authors' laboratory has determined that the human papillomavirus may be the viral aetiology of these skin lesions. The p53 tumor-suppressor gene is the most frequently mutated gene in a wide range of human cancers. Here the authors describe an immunohistochemical study to evaluate the expression of p53 in benign and malignant skin lesions from renal transplant recipients and immunocompetent patients with skin cancer. The effect of p53 mutations on the expression patterns observed were examined by polymerase chain reaction-single strand conformation polymorphism analysis and direct cycle sequencing. The expression of the p53-regulated cyclin-dependant kinase inhibitor p21Waf1/Cip1 and Mdm2 was also examined in p53-positive cells. The expression of p53 in benign and malignant lesions was found to be markedly different. p53 was expressed in only 40% (6/15) of viral warts analyzed. The expression was confined to the basal layer both in the lesion and in adjacent normal skin, and the level of expression was low and only in a small number of cells (<10%). Of the cutaneous squamous cell carcinomas analyzed, 60% (9/15) showed p53 expression. Two different patterns of expression were observed. Basal layer expression in both the invasive tumor and adjacent normal skin was observed in 50% of the p53-positive squamous cell carcinomas; in the remaining 50%, p53 was expressed diffusely throughout the invasive tumor and in the basal layer of adjacent normal skin. The level of expression was high and in a large number of cells. Polymerase chain reaction-single strand conformation polymorphism analysis revealed that only one of the squamous cell carcinomas expressing p53 harbored a p53 mutation and that the accumulated p53 in the remaining tumors was wild type. No Mdm2 or p21Waf1/Cip1 expression was detected in the p53-positive squamous cell carcinomas, indicating that although the accumulated p53 is stable, it does not function effectively as a transcriptional activator. This represents a novel p53 phenotype in cutaneous squamous cell carcinoma. In addition, no correlation was seen between the presence and absence of human papillomavirus and p53 expression.

Carcinoma, Squamous Cell↗
PubMed2001

CD44V6 in gastric carcinoma: a marker of tumor progression.

CD44 is a group of cell surface molecules involved in cell-cell and cell-matrix interactions. CD44 spliced variants (CD44V) have been found to enhance the metastatic potential of rat tumors. Tumors from the breast, colon, and thyroid express many alternatively spliced products; nonneoplastic tissues do not. Some authors suggest that CD44V5 and V6 may play a role in gastric carcinoma. The aim of the current study was to investigate the role of CD44V6 as a prognostic marker and predictor of metastatic potential in gastric carcinomas. One hundred fifty-five cases of gastric adenocarcinomas were studied: 36 cases of early (EGC), 19 cases of intermediate (MGC), and 100 cases of advanced gastric adenocarcinomas (AGC). A monoclonal antibody against CD44V6 (R&D) was used. CD44V6 expression was positively correlated with advanced stage (P = 0.05). Strong positivity was only detected in those cases of AGC with metastases. Patients with CD44V6 positive tumors revealed a lower 3- and 5-year survival rate (P = 0.0002). Immunohistochemical detection of CD44V6 could now be used as an indicator of tumor progression in biopsies of patients with gastric carcinoma.

Adenocarcinoma↗
PubMed2001

p53 codon 72 polymorphism and human papillomavirus associated skin cancer.

BACKGROUND/AIMS: Non-melanoma skin cancers frequently harbour multiple human papillomavirus (HPV) types. A recent report suggests that a polymorphism of the p53 tumour suppressor gene that results in the substitution of a proline residue with an arginine residue at position 72 of the p53 protein might act as a risk factor in HPV associated malignancies. This study aimed to determine the following: (1) the relation between HPV infection and the development of cutaneous squamous cell carcinoma (SCC), and (2) whether there is a correlation between p53 codon 72 polymorphism and the development of SCC. METHODS: Blood samples were taken from 55 patients with skin cancer (both renal transplant recipients and immunocompetent patients with skin cancer) and 115 ethnically matched volunteers. A polymerase chain reaction based assay was used to determine p53 codon 72 genotypes. In addition, 49 benign and malignant lesions from 34 of the patients with skin cancer and 20 normal human skin samples from 20 of the control volunteers were examined for HPV. RESULTS: The proportions of p53 codon 72 genotypes found were 78% arginine homozygous, 2% proline homozygous, and 20% heterozygous among patients with skin cancer and 79% arginine homozygous, 3.5% proline homozygous, and 17.5% heterozygous among the control population. Statistical analysis showed no significant differences in the distribution of the two p53 isoforms between the patients with skin cancer and the control population. The predominant viral types detected in both the patients and the control group were EV associated HPVs, although the incidence was lower in normal skin samples than in malignant lesions or viral warts. CONCLUSIONS: These results suggest that in a Celtic population there is no correlation between the presence of HPV, the p53 codon 72 arginine polymorphism, and the development of skin cancer.

Carcinoma, Squamous Cell↗
PubMed2001

A high degree of chromosomal instability at 13q14 in cutaneous squamous cell carcinomas: indication for a role of a tumour suppressor gene other than Rb.

BACKGROUND/AIMS: Loss of function of the retinoblastoma (Rb) tumour suppressor gene, located on chromosome 13, is common in many inherited and sporadic forms of cancer. Inactivation of its gene product by oncogenic human papillomaviruses (HPV) plays a key role in the genesis of cervical cancer. It has been shown previously that non-melanoma skin cancers of renal transplant recipients and immunocompetent patients with skin cancer also frequently harbour potentially oncogenic HPV types. This study aimed to examine the integrity of the Rb gene in histologically confirmed squamous cell carcinomas (SCCs) from renal transplant recipients and immunocompetent patients with skin cancer. METHODS: Loss of heterozygosity (LOH) at the Rb locus was examined in 13 histologically confirmed SCCs using the D13S153 microsatellite marker, which is located in exon 2 of the Rb gene. Loss of a second marker, D13S118, distal telomerically to the Rb gene at 13q14.3 was also analysed. RESULTS: Of the 13 HPV associated SCCs examined 11 were informative (two SCCs were homozygous for both microsatellite markers). LOH at the D13S153 locus was found in four of the 10 informative SCCs and LOH at the D13S118 locus was found in five of the 11 informative cases. Overall, seven of the 11 informative cases showed LOH at one or other locus. This represents a high degree of chromosomal instability in these tumours. The expression of the Rb gene product in the 11 informative cases was analysed immunohistochemically. Expression of Rb was detected in 10 of the 11 SCCs examined. No correlation between the HPV status of the tumours and the expression of Rb was found. Although the only SCC not to express Rb also demonstrated LOH at the D13S153 locus, the remaining SCCs that had LOH at 13q14 were able to express RB: CONCLUSION: Another tumour suppressor gene located at 13q14 might be responsible for the genesis of these tumours.

Carcinoma, Squamous Cell↗
PubMed2000

Immunohistochemical expression of nm23 in primary invasive malignant melanoma is predictive of survival outcome.

The objective of this study was to determine the utility of nm23 as an immunohistochemical indicator of prognosis in a large series (157 cases) of malignant melanoma and also in two subsets within this group: stage 1 tumours, whether in radial or vertical growth phase (140 cases); and stage 1 tumours in which a vertical growth phase component was positively identified (123 cases). A secondary objective was to explore the relationship between the immunohistochemical expression of nm23 and established clinical and histological indicators of prognosis in each of these three groups. In all groups it was found that strong immunoreactivity correlated positively with survival and inversely with indicators of poor prognosis, in keeping with transfection and mRNA studies and also with many immunohistochemical studies of other tumour types. That these findings are at variance with earlier reported immunohistochemical studies of melanoma highlights the importance of large case numbers of primary invasive tumours in studies which set out to explore the relationship between immunoreactivity and survival.

Analysis of Variance↗
PubMed2000

Deletion of the FHIT gene in neoplastic and invasive cervical lesions is related to high-risk HPV infection but is independent of histopathological features.

The fragile histidine triad (FHIT) gene encompasses the common chromosomal fragile site FRA3B. Human papilloma virus (HPV), which is the main aetiological agent in cervical cancers, has been found to be able to integrate its genes into the chromosome 3 fragile site of cultured cells, deleting a piece of DNA which includes the FHIT gene. Eighty-six microdissected archival cervical LLETZ biopsies comprising cases of cervical intraepithelial neoplasia (CIN) 1 (n=27), CIN3 (n=30) and microinvasive carcinoma (n=29) were evaluated for HPV infection and FHIT gene loss of heterozygosity (LOH). FHIT gene LOH was detected by polymerase chain reaction (PCR) using fluorescently labelled intragenic microsatellite markers D3S1300 and D3S4103. PCR products were analysed on a semi-automated DNA sequencer using Fragment Manager(trade mark) software to determine allele loss. The HPV status of the lesions was determined by PCR using generic and type-specific primers in conjunction with restriction endonuclease digestion. The results were analysed using Epi-Info and SPSS-PC statistical analysis software. Haematoxylin and eosin-stained sections from the 86 cases were profiled for six histopathological features, some of which have been previously shown to be associated with microinvasive cancer. FHIT gene LOH was found in 36% of CIN1 cases, 52% of CIN3 cases and 73% of microinvasive cases (p=0.029). HPV 16 DNA was found in 68% of CIN3 cases and 93% of microinvasive cases (p<0.001). The second most prevalent HPV type found was HPV 31, which was present in only four lesions, three of which had FHIT gene LOH. When FHIT gene LOH was evaluated versus HPV 16 and 31 infection using the chi-square test, a statistically significant relationship was found (p=0.014). FHIT gene LOH was found to be independent of the histopathological features evaluated. The finding of a statistically significant relationship between FHIT gene LOH and oncogenic HPV infection suggests a link between the integration of viral DNA and subsequent gene deletion in the progression of cervical cancer. FHIT gene anomalies may prove to be excellent markers of progression in early uterine cervical cancers.

Acid Anhydride Hydrolases↗
PubMed2000

Replication error phenotype, clinicopathological variables, and patient outcome in Dukes' B stage II (T3,N0,M0) colorectal cancer.

AIMS: To examine the relation between the replication error (RER) phenotype and other genetic events, clinical features, and long term survival in patients with Dukes' B stage II (T3,N0,M0) colorectal cancer. METHODS: RER phenotype was investigated in 159 patients by PCR amplification of microsatellite marker loci on chromosomes 5q, 17p, 17q, and 18q from tumour DNA extracted from archival tissue. Data on activating c-Ki-ras mutations were available from a previous study. Immunohistochemical detection of p53 and c-erbB-2 expression was performed on paraffin wax embedded tissue. RESULTS: Of 159 colorectal cancers studied, 22 (14%) were RER+ while 137 (86%) were RER- for two or more loci. RER+ tumours were more commonly located in the right colon, tended to be larger than RER- tumours, and were more often poorly differentiated than RER- cancers. No significant associations were seen between RER status and the presence of a mutant c-Ki-ras gene, or between RER status and p53, c-erbB-2, or c-myc gene expression. Univariate survival analysis showed that outcome was similar in RER+ and RER- cases. Multivariate survival analysis showed that the relative risk of death for patients with RER+ cancers was 0.95 that of patients with RER- cancers. CONCLUSIONS: The results suggest that, while the RER phenotype may be associated with some differences in tumour pathology (site, size, differentiation), it is not associated with the genetic alterations studied or with significant differences in long term survival.

Aged↗
PubMed2000

Catecholamine secretion and ploidy in phaeochromocytoma.

The aim was to evaluate 24 hr urine catecholamine, HMMA and HVA excretion in relation to ploidy in phaeochromocytoma. Data from five diploid and nine tetraploid tumours showed a significant reduction in urine noradrenaline (p = 0.02) and HMMA (p = 0.03) in diploid tumours but no difference in adrenaline, dopamine and HVA excretion using the Mann-Whitney U test. None of the patients showed recurrence after a mean of 5.7 years of follow up. A review of published ploidy studies in phaeochromocytoma shows that malignancy is more than six times more common in non-diploid tumours but diploidy does not equate with benignity. No biochemical marker is a reliable index of malignancy. All patients should undergo lifetime review for recurrence.

Adrenal Gland Neoplasms↗
PubMed1999

Renal cell carcinoma presenting as a pseudo-carcinoid tumour.

A 38-year-old woman presented with hypertension and a renal cell carcinoma. Raised urinary 5-hydroxyindoleacetic acid values >300 micromol/l, predictive of carcinoid tumour, were found during the perioperative period. The values returned towards normal 2 weeks post-surgery. Immunohistochemical examination of the renal cell carcinoma with neuroendocrine markers was negative. Despite a diligent search, no carcinoid tumour could be identified and the patient was well 4 years later. There was no dietary or drug explanation for this pseudocarcinoid.

Adult↗
PubMed1998

Altered expression of the p53-regulated proteins, p21Waf1/Cip1, MDM2, and Bax in ultraviolet-irradiated human skin.

The distribution of p21WAf1/CiP1, MDM2, and Bax/Bcl-2 proteins in ultraviolet (UV)-irradiated and nonirradiated human skin was examined immunohistochemically and compared with p53 protein levels. Sun-protected buttock skin from three volunteers was exposed to solar simulated irradiation, and biopsies were performed 0.5, 1, 2, 4, and 24 hours after irradiation as well as control unirradiated skin from the opposite buttock. A similar staining pattern was observed in each of the three volunteers. P53 protein was detectable in all skin samples examined. P21Waf1/CiP1 protein was visible in the nuclei of cells at 4 hours, and staining intensity increased at 24 hours. MDM2 protein expression was noted in isolated nuclei in the epidermis at 24 hours. Bax cytoplasmic staining was evident in the basal layer of the epidermis of all samples, and this staining appeared to increase in intensity in the 4- and 24-hour specimens. There was no Bcl-2 immunohistochemical staining in any sample. These results suggest that p53 and genes/proteins under the control of p53 are altered/ activated in normal human skin in response to UV exposure.

Aged↗
PubMed1998

Identification of vertical growth phase in malignant melanoma. A study of interobserver agreement.

Ninety-four H & E-stained slides of malignant melanoma were circulated to 6 pathologists in 2 university departments. For each slide, the growth phase of the lesion, Breslow thickness, and Clark level were determined by each observer. The aims of the study were to evaluate agreement between nonspecialist pathologists in identifying the vertical growth phase in malignant melanoma and to compare agreement for the growth phase with agreement for Breslow thickness and the Clark level. Our results show that although overall agreement for the growth phase is moderate, agreement between experienced observers is good. In fact agreement for the growth phase among this group was equal to the agreement for Breslow thickness. Overall agreement for Breslow thickness also was good but for the Clark level was only fair. These findings suggest that if the predictive value of the vertical growth phase proves to be robust, it will be used with an acceptable level of accuracy in routine diagnostic practice.

Humans↗
PubMed1998

Autoimmune chronic active hepatitis associated with the presence of antiphospholipid antibodies.

We report a patient with clinical, biochemical and immunological indices suggestive of autoimmune hepatitis with marked transaminasaemia, raised immunoglobulins and positive anti-nuclear and anti-smooth muscle antibodies. A coagulation screen revealed a transient, markedly increased, activated, partial thromboplastin time and a normal prothrombin time, with elevated levels of anticardiolipin antibodies and the presence of lupus anticoagulant, indicating the presence of antiphospholipid antibodies. Subsequent histology confirmed moderate hepatitis with piecemeal necrosis and fibrosis. Appropriate autoimmune therapy was commenced. This presentation illustrates the rare association of anti-phospholipid antibodies with autoimmune chronic active hepatitis presenting with a temporarily abnormal coagulation screen.

Actins↗
PubMed1998

Low-dose retinoid therapy for chemoprophylaxis of skin cancer in renal transplant recipients.

BACKGROUND: Renal transplant recipients have an increased incidence of skin cancers, which may be multiple and aggressive. OBJECTIVES: The purpose of this study was to examine the chemoprophylactic effects of low-dose etretinate (0.3 mg/kg/day) on skin cancer development in renal transplant recipients and to monitor retinoid toxic effects at this dose. METHODS: All skin lesions were counted and photographed prior to therapy with etretinate. Patients were assessed at monthly intervals for new skin lesions and for retinoid toxicity. RESULTS: Eleven renal transplant recipients participated. There was a significant reduction in the number of skin cancers which occurred during etretinate therapy compared with pre-treatment for 3 and 6 months of treatment, and a trend towards fewer skin cancers in the 12 and 18 month treatment periods. Side-effects were well-tolerated and no significant biochemical effects were observed. CONCLUSION: Low dose etretinate is safe, well-tolerated and partially effective in chemoprophylaxis of skin cancer in renal transplant recipients.

Adult↗
PubMed1998

Langerhans cells in benign, premalignant and malignant skin lesions of renal transplant recipients and the effect of retinoid therapy.

BACKGROUND AND DESIGN: Langerhans cells (LC) are a unique population of antigen-presenting cells in the epidermis which may play a role in the defense mechanisms against skin tumors. Renal transplant recipients (RTRs) have a significantly increased incidence of premalignant and malignant skin lesions. Langerhans cells, which are important for local immune surveillance, may be depleted or downregulated in skin neoplasms of RTRs, facilitating their growth. We investigated the Langerhans cell densities in 29 squamous cell carcinomas (SCCs), five basal cell carcinomas (BCCs), four Bowen's disease, eight dysplastic lesions (actinic keratoses), and three viral warts from 15 RTRs and compared these to the Langerhans cell densities in normal control skin. Eleven RTRs were receiving low-dose etretinate as chemoprophylaxis for recurrent skin cancer and the effect of low-dose retinoid therapy on Langerhans cell densities in SCCs from these patients was also assessed. Langerhans cells in frozen tissue sections were stained with the anti-human Leu-6 monoclonal antibody. RESULTS: There was no significant difference in LC numbers between normal skin from RTRs and normal skin from non-immunosuppressed individuals. There was a statistically significant reduction in LC/mm2 and LC/1000 K (keratinocytes) for SCC, BCC, dysplastic lesions and viral warts compared with normal skin (P < 0.001, P < 0.01, P < 0.001, P < 0.05, respectively). There was a trend for an increase in Langerhans cell density in SCCs which developed during etretinate therapy compared with pre-etretinate but the difference was not statistically significant. CONCLUSIONS: In this study of RTRs, a significant reduction in Langerhans cell densities was observed in SCCs, BCCs and dysplastic lesions compared with normal skin. A reduction in Langerhans cell density in viral warts from RTRs was also observed. A working hypothesis may include a multifactorial etiology for this reduction in Langerhans cell densities. It is possible that human papilloma virus (HPV) infection, by reducing intraepidermal Langerhans cell density, may decrease local immune surveillance and facilitate the development of skin cancers. Ultraviolet radiation and immune suppression may also play a role. The marked depletion of Langerhans cells in skin cancers, precursor lesions and viral warts suggests a central role for Langerhans cells in skin cancer promotion in RTRs.

Basal Cell Carcinoma↗
PubMed1997

p53 tumor suppressor gene protein expression in premalignant and malignant skin lesions of kidney transplant recipients.

BACKGROUND: Kidney transplant recipients have an increased incidence of skin cancer, the cause of which is likely multifactorial. Inactivation of the tumor suppressor gene p53 protein may be important. Chemoprophylaxis of skin cancer with retinoids is beneficial in these patients. OBJECTIVE: Our purpose was to investigate the immunohistochemical expression of p53 protein in premalignant and malignant cutaneous lesions in kidney transplant recipients and the effect of low-dose etretinate on p53 expression. METHODS: Paraffin sections were stained with the monoclonal antibody DO-7. RESULTS: Immunoreactivity of p53 was observed in 59% of basal cell carcinomas and more than 60% of squamous cell carcinomas, Bowen's disease, dysplastic lesions, and viral warts. No demonstrable effect of etretinate on p53 expression could be determined. CONCLUSION: The high prevalence of p53 immunoreactivity in premalignant and malignant skin lesions of kidney transplant recipients supports a role for p53 protein in skin cancer. This could be caused by mutation of the p53 gene, inactivation, or failure of degradation of p53 protein.

Adult↗