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A C Bateman

Publications and source records attributed to A C Bateman.

At least 37 records · Page 2Linked to original sources
PubMed2001

IL-10 promoter polymorphisms influence tumour development in cutaneous malignant melanoma.

Cutaneous malignant melanoma (CMM) is the most serious cutaneous malignancy. CMM patients often develop an immune response to their tumours. Conflicting evidence suggests that IL-10 may contribute to tumour escape from the immune response, but may also have an anti-tumour effect. To distinguish between these models and to determine whether genotypes associated with differential IL-10 expression confer susceptibility to and/or influence prognosis in CMM, 165 CMM patients and 158 controls were genotyped for IL-10 promoter SNPs by ARMS-PCR. The IL-10--1082 AA low expression genotype was increased in incidence among CMM patients (P = 0.04). In addition, IL-10 genotypes showed significant associations with three of four prognostic indicators examined; IL-10--1082 GG (P = 0.02) and -1082, -819 and -592 compound high expression (P = 0.03) genotypes were associated with horizontal (non-invasive) tumour growth; IL-10--1082 AA low expression genotype was associated with more advanced (Stage II-IV) disease (P = 0.04); finally, the IL-10--1082 AA (P = 0.005) and compound low expression (P = 0.009) genotypes were significantly increased in frequency among patients with thicker primary Vertical growth phase tumours. These results indicate that genotypes associated with high levels of IL-10 expression in vitro are protective in CMM, while low expression genotypes are a risk factor for more advanced/poorer prognosis disease and may confer susceptibility to CMM. Although the influence of IL-10 on melanoma development is likely to be complex, these results support recent findings that IL-10 has an anti-tumour effect in CMM, possibly via inhibition of angiogenesis.

Base Sequence↗
PubMed2001

Oncofetal fibronectin and oral squamous cell carcinoma.

Fibronectin is a cell matrix glycoprotein, which exists as a number of isoforms that are often found within the cell matrix that surrounds tumours. Collectively these tumour-associated isomers of fibronectin have been termed oncofetal fibronectin (OFFN). We looked for expression of OFFN within oral squamous cell carcinomas (SCC) and related its presence to prognosis. The investigation used a monoclonal antibody (MoAb 5C10) to the glycosylated variant of OFFN, and 100 archival specimens of oral SSC. Immunostaining for OFFN was intense in the adjacent stroma of 43 squamous carcinomas, weak in 27 and absent in 30. Cervical metastases were found in 17/27 (63%) specimens that stained intensely, 6/17 (35%) that stained weakly and 3/13 (23%) that did not stain. Of the 21 cases which had extracapsular lymph node spread, 81% were from those that stained intensely, 19% from those that stained weakly and none from those that did not stain for OFFN expression. Also, 21/44 patients (49%) died in group with intense OFFN staining, 6/26 (23%) in the group with weak staining and 3/30 (10%) in the group that did not stain. The presence of OFFN glycoprotein in oral SCC as evaluated by immunostaining with MoAb 5C10 correlates strongly with the presence of metastatic lymph node involvement, particularly extracapsular involvement, and mortality. We therefore suggest that the degree of expression of OFFN in tumours is a valuable prognostic indicator.

Biomarkers, Tumor↗
PubMed2001

The role and histological classification of needle core biopsy in comparison with fine needle aspiration cytology in the preoperative assessment of impalpable breast lesions.

AIMS: To investigate the role of needle core biopsy (NCB) in the preoperative assessment of impalpable breast lesions, mainly derived from the NHS Breast Screening Programme (NHSBSP) and to assess our own modifications to a suggested system for the classification of breast NCBs. METHODS: The NCB, fine needle aspiration cytology (FNAC), and radiology scores from 298 women with non-palpable breast lesions presenting between January 1997 and December 1998, together with the open biopsy results (where available) were collated and analysed. RESULTS: The mean follow up period was 15.8 months (range, 5-28). The 298 NCB specimens were categorised as follows: unsatisfactory/non-representative (B1; n = 61; 20.5%), benign but uncertain whether representative (B2r; n = 52; 17.4%), benign (B2; n = 103; 34.6%), lesions possibly associated with malignancy but essentially benign (B3a; n = 9; 3.0%), atypical epithelial proliferations (B3b; n = 10; 3.4%), suspicious of malignancy (B4; n = 7; 2.3%), and malignant (B5; n = 56; 18.7%). Excision biopsy was performed in 43 cases within the B1 (n = 19), B2r (n = 8), B2 (n = 8), and the B3a (n = 8; data unavailable in one case) categories, revealing malignancy in 18 (42.8%) cases and in 65 cases within the B3b, B4, and B5 categories, revealing malignancy in 64 cases (98.5%). The sensitivity of NCB for malignancy was 87.7%, with a specificity and positive predictive value of 99.3% and 98.5%, respectively. FNAC had an inadequacy rate of 58.7%, a complete sensitivity of 34.5% and a specificity of 47.6%. CONCLUSIONS: This study confirms the value of NCB in the preoperative assessment of impalpable breast lesions. Two new categories are suggested for the NCB classification; category B2r for benign breast tissue where representativeness is uncertain, and the subdivision of category B3 into B3a for benign lesions potentially associated with malignancy (for example, radial scars and intraduct papillomas) and B3b for more worrisome atypical epithelial proliferations. These will aid the accurate audit of NCB and identify more clearly the intellectual pathway leading to a particular assessment.

Aged↗
PubMed2001

Predominant fatty variant of myofibroblastoma of breast.

Myofibroblastoma of the breast is an uncommon but well defined benign stromal tumour. This report describes a case in which the predominant histological component was mature adipose tissue and two further cases with a major adipocytic component. Although small foci of adipose tissue are a recognised feature of this tumour, the dominance of the histological pattern by fat has not been described previously, and the recognition of this variant is important to allow confident diagnosis and avoid confusion with other primary adipocytic or stromal lesions, especially in the setting of potential needle core biopsy of such a lesion.

Adipocytes↗
PubMed2000

Anatomical basis for impotence following haemorrhoid sclerotherapy.

Impotence has been reported as a rare but important complication of sclerotherapy for haemorrhoids. The relationship between the anterior wall of the rectum and the periprostatic parasympathetic nerves responsible for penile erection was studied to investigate a potential anatomical explanation for this therapeutic complication. A tissue block containing the anal canal, rectum and prostate was removed from each of six male cadaveric subjects. The dimensions of the components of the rectal wall and the distance between the rectal lumen and parasympathetic nerves in the periprostatic plexus were measured in horizontal transverse histological sections of the tissue blocks at the level of the lower prostate gland (i.e. the correct level for sclerosant injection). The correct site of sclerosant in the submucosa was on average 0.6 mm (SD 0.3 mm) deep to the rectal mucosal surface and only 0.7 mm (SD 0.5 mm) in thickness. The nearest parasympathetic ganglion cells were a mean of only 8.1 mm (SD 2.0 mm) deep to the rectal lumen. The close proximity of the rectum to the periprostatic parasympathetic nerves defines an anatomical basis for impotence following sclerotherapy. This emphasises the need for all practitioners to be particularly careful when injecting in this area and for strict supervision of trainees.

Aged↗
PubMed1999

Human leukocyte antigens and cancer: is it in our genes?

Human leukocyte antigens (HLAs) are widely expressed cell surface molecules which present antigenic peptides to T-lymphocytes, thus modulating the immune response. The efficiency of peptide presentation by HLAs is dependent on the extreme polymorphism in the HLA-encoding loci within the major histocompatibility complex (MHC). HLA polymorphism is known to alter disease susceptibility and progression in a range of predominantly inflammatory conditions, many of which are T-lymphocyte-mediated. More recently, the importance of alterations in HLA expression and polymorphisms within HLA-encoding loci has emerged in the development of malignancy. This review concentrates on the role of HLA polymorphism in malignant disease, with discussion of the major cancers in which HLA associations have become clear, as well as the potential mechanisms by which HLA polymorphisms may act as important factors, or cofactors, in the pathogenesis of malignant disease. In addition, the role of certain non-HLA genes within the MHC in the pathogenesis of malignancy is also considered briefly.

Cell Transformation, Neoplastic↗
PubMed1999

Severe pulmonary toxicity in patients treated with a combination of docetaxel and gemcitabine for metastatic transitional cell carcinoma.

BACKGROUND: Both gemcitabine and docetaxel have been associated with pulmonary toxicity when used as single agents. We report a study in which three of five cases developed pulmonary toxicity (which proved fatal in one case) when these drugs were used in combination to treat metastatic transitional cell cancer. PATIENTS AND METHODS: Three patients developed dyspnoea, in two cases associated with pulmonary infiltrates, whilst receiving the combination of gemcitabine and docetaxel in a phase I trial. The case notes of all five patients entered into this trial were studied. A literature review was undertaken to gain information on reported pulmonary toxicity with the deoxy-cytidine analogues and taxanes given alone or in combination with or without radiotherapy. RESULTS: Three patients developed delayed dyspnoea whilst receiving gemcitabine/docetaxel in combination. This settled with cessation of treatment in one patient, however in the remaining two cases significant hypoxia developed, associated radiologically with evidence of progressive pulmonary infiltrates. One of these patients developed respiratory failure after bronchoscopy and biopsy and died. His chest X-ray changes were consistent with adult respiratory distress syndrome. The transbronchial biopsy and post mortem lung histology in this patient showed diffuse alveolar damage. The remaining patient settled with high dose prednisolone but died subsequently of progressive metastatic disease. CONCLUSION: The combination of gemcitabine and docetaxel showed promising activity in this small study. The development of pulmonary symptoms in three cases with radiological lung infiltrates in two other cases was cause for concern. Patients receiving this drug combination should be closely monitored for similar problems.

Aged↗
PubMed1999

Polymerase chain reaction based human leucocyte antigen genotyping for the investigation of suspected gastrointestinal biopsy contamination.

BACKGROUND: Mislabelling or contamination of surgical specimens may lead to diagnostic inaccuracy, particularly within gastrointestinal pathology when multiple small mucosal biopsy specimens are commonly taken, and where a tiny fragment of foreign tissue may be indistinguishable from true biopsy material using histological assessment alone. AIMS: To assess the utility of polymerase chain reaction (PCR) based human leucocyte antigen (HLA) genotyping techniques for the investigation of potentially mislabelled or contaminated gastrointestinal biopsy specimens. PATIENTS: Ten cases (28 samples) in which mislabelling or contamination was suspected, comprising four upper gastrointestinal tract biopsies and six colonoscopic biopsy series. METHODS: Direct and nested PCR-sequence specific primer (SSP) based HLA class II genotyping was performed on DNA extracted from formalin fixed and paraffin wax embedded tissue (23 samples) or peripheral blood leucocytes (five samples). RESULTS: A full HLA-DRB1 genotype was determined in all 28 samples. In seven cases the HLA-DRB1 genotype of the putative contaminant was different to that of the corresponding reference tissue, confirming different individual origins for the contaminant and reference material. In one case the contaminant tissue was shown to possess the same HLA-DRB1 alleles as a second patient (probable source). In the remaining three cases the same HLA-DRB1 alleles were detected within the potential contaminant and reference tissues. CONCLUSIONS: PCR based HLA class II genotyping is a valuable tool for investigating potential contamination or mislabelling within gastrointestinal biopsy specimens and this report has confirmed contamination in seven of ten cases studied.

Adult↗
PubMed1999

HLA class II DRB1 and DQB1 allelic polymorphism and sclerosing lymphocytic lobulitis of the breast.

BACKGROUND: Sclerosing lymphocytic lobulitis is an inflammatory disorder of the breast. The pattern of inflammation, expression of HLA class II DR by breast epithelium and association with autoimmune disorders, particularly insulin dependent diabetes mellitus (IDDM), together suggest an autoimmune aetiology. AIM: To test the hypothesis that susceptibility to sclerosing lymphocytic lobulitis may be linked to patient HLA class II DRB1 alleles, particularly DRB1*03 and DRB1*04, suggested by a previous small uncontrolled study. METHODS: HLA class II DRB1 and DQB1 genotypes were compared between a series of 28 sclerosing patients with lymphocytic lobulitis and 300 controls, using polymerase chain reaction (PCR) based typing of DNA extracted from formalin fixed, paraffin embedded biopsies. RESULTS: Results from the 28 patients (nine with IDDM) showed an increased frequency of DRB1*04 compared with controls (61% v 33%, p = 0.01), but no significant differences for other genotypes. In patients with IDDM, the frequencies of DRB1*04 (89%, p = 0.001) and DQB1*0302 (100% v 21%, p = 0.0001)--a genotype that is in linkage disequilibrium with DRB1*04--were increased compared with controls. However, in the patients without IDDM, the frequencies of DRB1*04 (50%) and DQB1*0302 (14%) were not significantly increased. CONCLUSIONS: The increased frequency of HLA DRB1*04 in sclerosing lymphocytic lobulitis appears to reflect its association with IDDM, a condition in which DRB1*04 is increased in frequency.

Adult↗
PubMed1998

HLA-DQB1*0303 and *0301 alleles influence susceptibility to and prognosis in cutaneous malignant melanoma in the British Caucasian population.

The presence of lymphocytic infiltrates within primary cutaneous malignant melanoma (CMM), documented spontaneous tumour regression and genetic linkage with chromosome six in familial cases all suggest that immunogenetic factors may modulate disease progression. An association has been suggested between HLA DQB1*0301 and CMM in US patients but no such investigation has been performed in the UK population. Polymerase chain reaction-based HLA class II DRB1, DQA1 and DQB1 typing of 99 UK-based CMM patients was performed using DNA extracted from archival formalin-fixed and paraffin wax-embedded surgical biopsies, enabling retrospective access to clinical follow-up data. An increase in frequency of the HLA DQB1*0303 genotype among CMM patients was identified compared to control subjects (19.2% vs 5.8%; Pc=0.003; RR=3.9) while HLA DQB1*0301 was associated with more advanced and therefore poorer prognosis primary tumours (e.g. HLA DQB1*0301 allele frequency: 20.1% vertical growth phase vs 4.0% horizontal growth phase; Pc=0.03; RR=6.1). These findings suggest that the HLA DQB1 locus, and in particular the HLA DQB1*0303 and *0301 alleles, may play an important role in determining the risk of development and the prognosis of CMM within the UK population.

Female↗
PubMed1997

Nested polymerase chain reaction-based HLA class II typing for the unique identification of formalin-fixed and paraffin-embedded tissue.

Human leukocyte antigen (HLA) genotyping is routinely performed prior to organ transplantation using peripheral blood leukocyte-derived DNA. In addition, polymerase chain reaction (PCR)-based methods have permitted HLA genotyping using DNA extracted from formalin-fixed and paraffin-embedded tissue, with proven applications in HLA-disease association studies and surgical biopsy identification. The utility of current techniques may be limited by the poor yield of intact DNA from such paraffin biopsies. This paper describes a new nested PCR-based HLA class II genotyping method which reliably detects HLA DRB alleles within DNA extracted from even extremely small paraffin biopsies. This method comprises initial PCR amplification of exon II sequences of the HLA DRB1, 3, 4, and 5 genes using generic PCR primers. Identification of the HLA DRB1 alleles and detection of the DRB3, 4, and 5 genes is then performed using a series of separate individual second-round PCR reactions, each of which contains PCR primer pairs detecting a single HLA DRB allele or group of alleles (PCR-SSP). The ability of this method to detect 19 individual HLA DRB1 alleles or groups of alleles, covering all common DRB1 specificities, was confirmed via concordant results when compared with 'direct' (single amplification step) PCR-SSP analysis of one cell line-derived and nine peripheral blood-derived DNA samples, and with five DNA samples extracted from paraffin biopsies. The technique was then successfully applied to 11 further paraffin biopsy-derived DNA samples, of which ten were untypable by 'direct' PCR-SSP analysis, from five cases in which doubt existed as to the individual origin of the tissues.

Adult↗
PubMed1997

Pre-operative localization of breast microcalcification using high-frequency ultrasound.

AIM: To determine whether high-frequency ultrasound (US) can be used to reliably localize breast microcalcification preoperatively in the absence of any associated mass lesion or distortion. PATIENTS AND METHODS: Seventeen patients, found to have microcalcification at mammography, the majority screen detected, were studied using high-frequency (10 or 13 MHz) US to visualize the calcified particles. The approximate site of the microcalcifications was first determined from the mammograms. Once the calcifications had been localized, the skin overlying the site was marked with an indelible marker and the depth of the calcifications recorded for the surgeon. Successful excision of microcalcifications was confirmed with postbiopsy specimen X-ray. RESULTS: Fifteen of the 17 patients (88%) underwent successful removal of the microcalcifications. The mean microcalcification cluster size was 160 mm with a mean number of calcifications of 20 at a mean depth of 15 mm. The mean size of the individual calcifications was 0.29 mm. CONCLUSION: Our results show that high-frequency US is an effective non-invasive method of identifying and localizing breast microcalcification, and can be used as an alternative to hook wire stereotaxic localization in the majority of patients.

Adult↗
PubMed1997

Rosai-Dorfman disease presenting as a parotid mass.

Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare, benign disease of unknown aetiology. This disease typically presents with massive, painless cervical lymphadenopathy but may occur in a wide variety of extranodal sites. Our report describes a 71-year-old man who presented with a discrete, unilateral parotid mass which was clinically suggestive of a primary salivary gland tumour. Initial cytological examination of a fine needle aspirate specimen taken from the mass demonstrated a discohesive cell population with nuclear atypia, raising the possibility of malignancy. However, excision of the mass and histological examination enabled a definitive diagnosis to be made.

Aged↗
PubMed1997

Immunohistochemical phenotype of malignant mesothelioma: predictive value of CA125 and HBME-1 expression.

Histological diagnosis of malignant mesothelioma and differentiation from adenocarcinoma is often difficult. Definitive pathological confirmation of malignant mesothelioma requires demonstration of an appropriate immunohistochemical phenotype. Selection of an optimum panel of immunohistochemical antibodies for the reliable identification of malignant mesothelioma is hindered by the absence of a specific immunohistochemical label for mesothelioma cells. Recently, we have found that the ovarian carcinoma cell antibody CA125 labels malignant mesothelioma cells, and the antibody HBME-1 has been developed as a sensitive mesothelial cell marker. We have compared the immunohistochemical staining patterns achieved with CA125 and HBME-1 to those obtained using a panel of eight further antibodies in 17 malignant mesotheliomas and 14 primary and secondary adenocarcinomas within lung and pleura. CA125 labelled malignant mesothelioma cells in 15 of 17 cases (88%), and adenocarcinoma cells in seven of 14 cases (50%). HBME-1 labelled mesothelioma cells in all 17 cases (100%) but also labelled adenocarcinoma cells in 10 of 14 cases (71%). BerEP4 positively labelled one malignant mesothelioma but was negative in the remaining 16 cases and positively labelled nine of 14 adenocarcinomas (64%). Monoclonal anti-CEA, AUA-1, CA19.9 and LeuM1 labelled no malignant mesotheliomas and were positive in 10 (71%), nine (64%), eight (57%) and six (43%) of 14 cases of adenocarcinoma, respectively. Diastase-PAS staining detected neutral mucin in none of the malignant mesotheliomas but in 10 (71%) of the 14 adenocarcinomas. We conclude that CA125 and HBME-1 do not label mesothelial cells with sufficient specificity to be useful for differentiating malignant mesothelioma from adenocarcinoma, although negative staining with HBME-1 makes a diagnosis of malignant mesothelioma unlikely. As there remains an absence of a specific positive mesothelial cell marker this distinction is still most reliably made using a panel of antibodies including at least two of the following: anti-CEA, AUA-1, BerEP4, LeuM1 and CA19.9, in combination with histochemical assessment of neutral mucin production.

Adenocarcinoma↗