PubMed Health⌕ Search

Biomedical subjects

L Bobrow

Publications and source records attributed to L Bobrow.

At least 19 recordsLinked to original sources
PubMed2006

Impact of a national external quality assessment scheme for breast pathology in the UK.

BACKGROUND: This article presents the results and observed effects of the UK National Health Service Breast Screening Programme (NHSBSP) external quality assurance scheme in breast histopathology. AIMS/METHODS: The major objectives were to monitor and improve the consistency of diagnoses made by pathologists and the quality of prognostic information in pathology reports. The scheme is based on a twice yearly circulation of 12 cases to over 600 registered participants. The level of agreement was generally measured using kappa statistics. RESULTS: Four main situations were encountered with respect to diagnostic consistency, namely: (1) where consistency is naturally very high-this included diagnosing in situ and invasive carcinomas (and certain distinctive subtypes) and uncomplicated benign lesions; (2) where the level of consistency was low but could be improved by making guidelines more detailed and explicit-this included histological grading; (3) where consistency could be improved but only by changing the system of classification-this included classification of ductal carcinoma in situ; and (4) where no improvement in consistency could be achieved-this included diagnosing atypical hyperplasia and reporting vascular invasion. Size measurements were more consistent for invasive than in situ carcinomas. Even in cases where there is a high level of agreement on tumour size, a few widely outlying measurements were encountered, for which no explanation is readily forthcoming. CONCLUSIONS: These results broadly confirm the robustness of the systems of breast disease diagnosis and classification adopted by the NHSBSP, and also identify areas where improvement or new approaches are required.

Breast Neoplasms↗
PubMed2006

The NHS breast screening programme (pathology) EQA: experience in recent years relating to issues involved in individual performance appraisal.

BACKGROUND: The original role of the National Health Service breast screening programme (pathology) external quality assessment (EQA) scheme was educational; it aimed to raise standards, reinforce use of common terminology, and assess the consistency of pathology reporting of breast disease in the UK. AIMS/METHODS: To examine the performance (scores) of pathologists participating in the scheme in recent years. The scheme has evolved to help identify poor performers, reliant upon setting an acceptable cutpoint. Therefore, the effects of different cutpoint strategies were evaluated and implications discussed. RESULTS/CONCLUSIONS: Pathologists who joined the scheme improved over time, particularly those who did less well initially. There was no obvious association between performance and the number of breast cancer cases reported each year. This is not unexpected because the EQA does not measure expertise, but was established to demonstrate a common level of performance (conformity to consensus) for routine cases, rather than the ability to diagnose unusual/difficult cases. A new method of establishing cutpoints using interquartile ranges is proposed. The findings also suggest that EQA can alter a pathologist's practice: those who leave the scheme (for whatever reason) have, on average, marginally lower scores. Consequently, with the cutpoint methodology currently used (which is common to several EQA schemes) there is the potential for the cutpoint to drift upwards. In future, individuals previously deemed competent could subsequently be erroneously labelled as poor performers. Due consideration should be given to this issue with future development of schemes.

Breast Neoplasms↗
PubMed2004

Radioguided occult lesion localisation (ROLL) and sentinel node biopsy for impalpable invasive breast cancer.

AIM: The aim of this study was to simplify the technique of ROLL and sentinel node biopsy without compromising tumour excision and sentinel node biopsy. METHODS: Twenty patients with impalpable primary invasive breast carcinoma underwent an injection of 99mTc-nanocolloid mixed with radiographic contrast medium Iohexol into the centre of the lesion under ultrasound or stereotactic guidance pre-operatively. No guidewire localisation was performed. Under general anaesthesia, a periareolar intradermal/subcutaneous injection of patent blue-V dye was performed. The sentinel node was identified by blue-stained lymphatics and node and a hot spot on the gamma probe. Surgical excision of the primary tumour was then carried out using the gamma probe. RESULTS: In eight of 20 cases an immediate re-excision was carried out and on histological assessment, all 20 patients were clear of invasive disease at the margins. In two patients, in situ disease was present at the margins and a further re-excision was therefore performed. The sentinel node was identified in all cases. In all, five of 20 patients were node positive on routine HE staining. In a further two patients, tumour cells were identified by immunohistochemistry with CAM5.2 antibody. Completion axillary clearance in six patients confirmed that the sentinel node was the only positive node. CONCLUSIONS: This modification of the previously described ROLL technique is feasible and safe and does not compromise tumour excision or sentinel node detection.

Aged↗
PubMed2001

Lobular carcinoma in situ on core biopsy-what is the clinical significance?

AIM: To retrospectively review the surgical histological findings in all cases where lobular carcinoma in situ(LCIS) was identified on percutaneous core biopsy (CB) performed as part of the Cambridge and Huntingdon breast screening programme. MATERIALS AND METHODS: We retrospectively reviewed all the core biopsies performed in our department for screen detected abnormalities over a 5-year period between 1 April 1994 and 31 March 1999. All patients where LCIS was identified on CB were reviewed. As the significance of LCIS on CB was unclear all went on to surgical excision. We reviewed the clinical and imaging findings, biopsy technique and subsequent surgical histology of each patient. RESULTS: During the study period 60 769 women were invited for screening, of whom 47 975 attended (attendance rate = 79%). Of these, 2330 (4.9%) were recalled for assessment and 749 (1.6%) underwent CB. A malignant diagnosis was obtained in 311 (42%), 211 invasive and 100 in situ lesions. LCIS was identified on CB in 13 (2%). LCIS was the only lesion identified in seven cases. All seven cases subsequently underwent surgical excision. Surgical histology revealed a single case of LCIS and invasive lobular carcinoma. There were two cases of LCIS and DCIS one with a probable focus of invasive ductal carcinoma. In one case LCIS was identified in association with a radial scar. In three of the seven cases LCIS was the only abnormality on both CB and surgical biopsy. CONCLUSION: Our series shows that isolated LCIS on CB following mammographic screening is an infrequent finding, and it may be associated with either an invasive cancer or DCIS. It is therefore advisable that when LCIS is identified on CB, surgical excision of the mammographic abnormality should be performed. Decisions on management should be undertaken in a multidisciplinary setting taking into account clinical and imaging findings.

Aged↗
PubMed2001

Sentinel lymph node biopsy in impalpable breast cancer.

Sentinel lymph node biopsy has been investigated using combined radioactive colloid and supra vital blue dye in 27 patients with impalpable breast cancers. Sentinel nodes were identified in 25 cases (93%). Seven patients had involved nodes of whom all had a positive sentinel node. Sentinel node biopsy is ideally suited for use in impalpable breast cancers.

Journal Article↗
PubMed2001

DNA replication licensing and human cell proliferation.

The convergence point of growth regulatory pathways that control cell proliferation is the initiation of genome replication, the core of which is the assembly of pre-replicative complexes resulting in chromatin being "licensed" for DNA replication in the subsequent S phase. We have analysed regulation of the pre-replicative complex proteins ORC, Cdc6, and MCM in cycling and non-proliferating quiescent, differentiated and replicative senescent human cells. Moreover, a human cell-free DNA replication system has been exploited to study the replicative capacity of nuclei and cytosolic extracts prepared from these cells. These studies demonstrate that downregulation of the Cdc6 and MCM constituents of the replication initiation pathway is a common downstream mechanism for loss of proliferative capacity in human cells. Furthermore, analysis of MCM protein expression in self-renewing, stable and permanent human tissues shows that the three classes of tissue have developed very different growth control strategies with respect to replication licensing. Notably, in breast tissue we found striking differences between the proportion of mammary acinar cells that express MCM proteins and those labelled with conventional proliferation markers, raising the intriguing possibility that progenitor cells of some tissues are held in a prolonged G1 phase or "in-cycle arrest". We conclude that biomarkers for replication-licensed cells detect, in addition to actively proliferating cells, cells with growth potential, a concept that has major implications for developmental and cancer biology.

Animals↗
PubMed2000

Can we be sure about a radiological diagnosis of fat necrosis of the breast?

AIMS: We performed a review of the clinical, mammographic and sonographic findings of fat necrosis in a group of patients who presented with a lump in the breast. We aimed to show that, in the light of a non-specific combination of findings, an ultrasound-guided core-biopsy (CB) is a safe, quick and useful test to confirm the diagnosis. The procedure makes it possible to reassure the patient of the true identity of the lesion, thus avoiding the need for surgical excision or follow-up investigations. MATERIALS AND METHODS: We undertook a retrospective review of the clinical presentation, imaging findings and subsequent management of 23 histologically proven cases of fat necrosis. All patients had presented to a specialist breast clinic with a breast lump. RESULTS: Only 52% of patients had a definite history of trauma. Clinical examination intimated that the lump was possibly malignant in 22%, while 4.5% were probably malignant. Fifty-seven per cent of mammograms were completely normal, however ultrasound showed an abnormality in 100%. Of these 100%, 74% were interpreted as possibly malignant. The diagnosis of fat necrosis was histologically confirmed by ultrasound-guided needle core biopsy, performed at the time of initial presentation. All patients were subsequently discharged. The mean time interval from investigation and biopsy to final diagnosis and discharge of the patient was 5.9 days. CONCLUSION: We show that fat necrosis often has a confusing clinical presentation. Imaging by either mammography or ultrasound is often inconclusive and ultrasound-guided core biopsy will confirm the diagnosis sparing patients unnecessary radiological follow-up or surgical excision.

Adult↗
PubMed1999

The genetic epidemiology of early-onset epithelial ovarian cancer: a population-based study.

We conducted a population-based study to determine the contribution of germline mutations in known candidate genes to ovarian cancer diagnosed at age <30 years. Women with epithelial ovarian cancer were identified through cancer registries. DNA samples were analyzed for mutations in BRCA1, the "ovarian cancer-cluster region" (nucleotides 3139-7069) of BRCA2, and the mismatch-repair genes hMSH2 and hMLH1. Probable germline mutations in hMLH1 were identified in 2 (2%; 95% confidence interval 1%-8%) of 101 women with invasive ovarian cancer diagnosed at age <30 years. No germline mutations were identified in any of the other genes analyzed. There were no striking pedigrees suggestive of families with either breast/ovarian cancer or hereditary nonpolyposis colorectal cancer (HNPCC). There was a significantly increased incidence of all cancers in first-degree relatives of women with invasive disease (relative risk [RR] = 1.6, P=.01) but not in second-degree relatives or in relatives of women with borderline cases. First-degree relatives of women with invasive disease had increased risks of ovarian cancer (RR = 4.8, P=.03), myeloma (RR = 10, P=.01), and non-Hodgkin lymphoma (RR = 7, P=.004). Germline mutations in BRCA1, BRCA2, msh2, and mlh1 contribute to only a minority of cases of early-onset epithelial ovarian cancer. Our data suggest that early-onset ovarian cancer is not associated with a greatly increased risk of cancer in close relatives.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Changing to core biopsy in an NHS breast screening unit.

We recently changed from using fine needle aspiration cytology to using core biopsy exclusively in the assessment of screen detected abnormalities. Two hundred and two biopsies (1% of women screened) were performed. Surgical histological confirmation was obtained in 111 patients (101 malignant and 10 benign). The remaining patients were either returned to standard 3-yearly screening or early repeat screening after 1 year. Analysis of the results was performed in accordance with the standards specified in the National Health Service Breast Screening Programme (NHSBSP) Publication Number 22. Absolute sensitivity was 89.3%, complete sensitivity was 93.2%, specificity (including patients undergoing both surgical excision and follow-up) was 88.7%. The predictive value of a positive (malignant) core biopsy result was 100%. The false negative rate was 3.9%. Twelve (5.9%) biopsies were classified inadequate for diagnosis. Core biopsy is a safe and accurate way of assessing screen detected abnormalities and can be used as a substitute for fine needle aspiration cytology with results that exceed the National Health Service Breast Screening Programme target standards, even in the learning phase.

Biopsy↗
PubMed1996

Sequence variants of the estrogen receptor (ER) gene found in breast cancer patients with ER negative and progesterone receptor positive tumors.

Thirteen pairs of tumor and blood DNAs from breast cancer patients with estrogen receptor (ER) negative and progesterone receptor (PgR) positive tumors were screened for mutation analysis using SSCP method. Although neither germline nor somatic mutation of the ER gene in this series was detected, we found two types of sequence variants in exon 1 and exon 4, indicating two silent mutations in codon 10 (TCT to TCC) and codon 325 (CCC to CCG), respectively. These variants were recognized as polymorphic sites. Although the frequency of these polymorphic sites was not correlated with hormone receptor status, the variant in codon 325 tended to be seen more frequently in breast cancer patients than in non-cancer control cases (P = 0.057).

Base Sequence↗
PubMed1995

Loss of heterozygosity of the oestrogen receptor gene in breast cancer.

DNA from 67 primary breast carcinoma biopsies has been examined for loss of heterozygosity (LOH) using the microsatellite (TA)n repeat marker positioned 1 kb upstream of the oestrogen receptor (ER) gene. Forty-seven (70.1%) of the cases were informative; nine of these (19.1%) were positive for LOH. In three of the nine cases, there was total loss, and in the other six cases there was a marked reduction in the intensity of signal from one allele. LOH correlated weakly with histological grade and age, but not with ER status. This result suggests that LOH of the ER gene does not have an important role in the lack of ER function in breast cancer tissues.

Base Sequence↗
PubMed1992

Monoclonal antibodies in the detection of bone marrow metastases in small cell lung cancer.

Using conventional examination (CE) of H&E stained slides from bone marrow aspirates, metastases can be detected in approximately 25% of patients with small cell lung cancer. We investigated a panel of monoclonal antibodies using immunohistochemistry in the diagnosis of bone marrow infiltration from SCLC and compared the results with CE. Seven monoclonal antibodies raised against epithelial antigens (CAM 5.2, MOV 15, NCCST 433, PE 35, LCA1/L38, HMFG 1 AND HMFG 2) were applied on bone marrow sections from three groups of patients (pts): (1) 19 pts in whom SCLC-metastases were detected by CE, (2) 44 pts with SCLC in whom metastases could not be detected by CE, and (3) 20 pts with non-malignant bone marrow diseases. All the antibodies except LCA1/L38 were positive in 60-90% of the slides with infiltrating tumour cells in group 1. No positive tumour cells were detected in group 2. A few plasma cells and megakaryocytes were slightly positive for MOV 15 and NCCST 433, but no other positive cells were detected in group 3. In conclusion, the monoclonal antibodies used in this study may be useful for diagnostic purposes when a suspicious looking infiltration is detected by CE. However, these antibodies could not detect metastatic tumour cells in the bone marrow sections from patients in whom CE did not reveal any tumour cells.

Antibodies, Monoclonal↗
PubMed1992

AUA1: new immunocytochemical marker for detecting epithelial cells in body cavity fluids.

Further to detailed genetic and biochemical characterisation of AUA1 as a surface glycoprotein present on epithelial cells, the antibody against AUA1 was used as an immunocytochemical marker of epithelial cells in body cavity fluids in an attempt to improve the diagnosis made on routine staining. AUA1 was initially tested in 144 morphologically clear cut effusions. It was positive in 46 of 52 (88%) carcinomas and negative in 82 of 84 (98%) benign effusions, including technically inadequate or poorly cellular preparations. There were no false positive results. AUA1 was subsequently used more selectively--that is, in 42 of 175 (24%) of morphologically difficult fluids. AUA1 provided essential diagnostic information in 15 of 42 (36%) and confirmed diagnosis in 17 of 42 (40%), thus enabling accurate diagnosis in a further 32 of 42 (76%) of the difficult cases. The total diagnostic accuracy was therefore 94.3%. AUA1 is a reliable immunocytochemical marker for detecting epithelial cells in body fluids. Its use improves diagnostic accuracy of morphological assessment in difficult cases.

Antibodies, Monoclonal↗
PubMed1991

The differential diagnosis of epithelial-type mesothelioma from adenocarcinoma and reactive mesothelial proliferation.

Three monoclonal antibodies (mAbs) have been applied to 14 adenocarcinomas, eight mesotheliomas, and nine reactive mesothelial proliferations. One of these, AUA1, is a novel antibody in this context. It was found in 13/14 of the adenocarcinomas but not in benign or malignant mesothelial tissue, making it a potential substitute for carcinoembyronic antigen (CEA) in the differential diagnosis of mesotheliomas from adenocarcinomas. In addition, the lesions were stained using an argyrophil technique to identify nucleolar organizer regions. The results of counting these showed a small but significant overlap in their numbers between malignant and benign mesothelial proliferations. Although there was a difference overall in the numbers of nucleolar organizer regions in adenocarcinomas and mesotheliomas, on the one hand, and benign hyperplasias, on the other, this overlap considerably reduces their value in assessing individual difficult cases.

Adenocarcinoma↗