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F Rank

Publications and source records attributed to F Rank.

At least 19 recordsLinked to original sources
PubMed2005

Radiation doses to staff involved in sentinel node operations for breast cancer.

BACKGROUND: The use of radioactive compounds for sentinel node biopsy is now a generally accepted part of the surgical treatment of breast cancer and melanoma, with the risk of radiation exposure to the operating team. The aim of this investigation was to study the levels of this exposure in relation to the permissible radiation dose limits. METHODS: The radiation exposure to the hands and bodies of the operating surgeons (the 'risk persons') was measured by thermoluminescent dosimeters in 79 operations and to the pathologists handling the specimens in 17 cases. Radioactivity and dose rate measurement from tumours and breast specimens were also performed. RESULTS: During an operation the mean skin dose (+/-SD) to the thermoluminescent dosimeters placed at the hand and the abdominal wall were 0.04 +/- 0.04 mSv (79 operations) and 0.01 +/- 0.02 mSv (67 operations) respectively. For the pathologist, the mean hand dose per operation was below the detection limit (17 operations). Correlation between the measured dose rate and the radioactive content of the tumours was 0.998. CONCLUSIONS: The radiation exposure to the staff involved in sentinel node (SN) biopsy for breast cancer using radioactive labelled tracers will be considerably below the permissible limits, even with high numbers of SN biopsy procedures. Pregnant staff members should participate in <100 SN operations.

Body Burden↗
PubMed2005

Intraoperative frozen section examination of axillary sentinel lymph nodes in breast cancer.

The study presents the results from intraoperative frozen section assessment of axillary sentinel lymph nodes (SLNs) in breast cancer. Routine histological frozen sections from one level were used, two sections stained with haematoxylin and eosin. Immunohistochemistry for cytokeratins was applied to the permanent SLN paraffin sections only. Axillary dissection was performed on all SLN-positive cases regardless of the size of the metastatic deposits. With a detection rate of 83%, 272 patients entered the study over a period of 46 months. A total of 61 cases were SLN positive by frozen section analysis. The paraffin sections gave an additional 23 SLN-positive cases. The false-negative rate for frozen sections was then 27% (23/84). Micrometastases were found in 28 of 84 cases, and macrometastases in 56. The false-negative rate of frozen sections for micrometastases was 71% (20/28), and for macrometastases 5% (3/56). A total of 73% (61/84) of the patients underwent axillary surgery as a one-step procedure.

Adult↗
PubMed2004

Breast cancer with different prognostic characteristics developing in Danish women using hormone replacement therapy.

The aim of this study is to investigate the risk of developing prognostic different types of breast cancer in women using hormone replacement therapy (HRT). A total of 10 874 postmenopausal Danish Nurses were followed since 1993. Incident breast cancer cases and histopathological information were retrieved through the National Danish registries. The follow-up ended on 31 December 1999. Breast cancer developed in 244 women, of whom 172 were invasive ductal carcinomas. Compared to never users, current users of HRT had an increased risk of a hormone receptor-positive breast cancer, but a neutral risk of receptor-negative breast cancer, relative risk (RR) 3.29 (95% confidence interval (CI): 2.27-4.77) and RR 0.99 (95% CI: 0.42-2.36), respectively (P for difference=0.013). The risk of being diagnosed with low histological malignancy grade was higher than high malignancy grade with RR 4.13 (95% CI: 2.43-7.01) and RR 2.17 (95% CI: 1.42-3.30), respectively (P=0.063). For breast cancers with other prognostic characteristics, the risk was increased equally for the favourable and non favourable types. Current users of HRT experience a two- to four-fold increased risk of breast cancer with various prognostic characteristics, both the favourable and non favourable types. For receptor status, the risk with HRT was statistically significantly higher for hormone receptor-positive breast cancer compared to receptor-negative breast cancer.

Aged↗
PubMed2004

Consistency of staining and reporting of oestrogen receptor immunocytochemistry within the European Union--an inter-laboratory study.

To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.

Breast Neoplasms↗
PubMed2004

Discrepancies in current practice of pathological evaluation of sentinel lymph nodes in breast cancer. Results of a questionnaire based survey by the European Working Group for Breast Screening Pathology.

AIMS: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. METHODS: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. RESULTS: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. CONCLUSIONS: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases > 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.

Biomarkers, Tumor↗
PubMed2003

Pathological work-up of sentinel lymph nodes in breast cancer. Review of current data to be considered for the formulation of guidelines.

Controversies and inconsistencies regarding the pathological work-up of sentinel lymph nodes (SNs) led the European Working Group for Breast Screening Pathology (EWGBSP) to review published data and current evidence that can promote the formulation of European guidelines for the pathological work-up of SNs. After an evaluation of the accuracy of SN biopsy as a staging procedure, the yields of different sectioning methods and the immunohistochemical detection of metastatic cells are reviewed. Currently published data do not allow the significance of micrometastases or isolated tumour cells to be established, but it is suggested that approximately 18% of the cases may be associated with further nodal (non-SN) metastases, i.e. approximately 2% of all patients initially staged by SN biopsy. The methods for the intraoperative and molecular assessment of SNs are also surveyed.

Breast Neoplasms↗
PubMed2002

Early outcome of mammography screening in Copenhagen 1991-99.

OBJECTIVES: To evaluate the early outcome of an organised mammography screening programme in an area with little opportunistic screening. SETTING: The municipality of Copenhagen, Denmark, during four invitation rounds 1991-99. METHODS: The following outcome measures were used: rates of participation, recall, false positive, and cancer detection. Benign biopsy, distribution of tumour size, lymph node status, and malignancy grade. RESULTS: A total of 106,933 screens were undertaken, and 824 invasive breast carcinomas or CIS were detected. The detection rate was 11.9 per 1000 participants in the first invitation round, and it continued to be high in subsequent rounds. The percentage of CIS cases was 11%. Coverage declined from 71% in the first round to 62% in the fourth, although 91% of those participating in the previous three rounds attended. The programme operated with a high recall rate. The false positive rate was also high, being 5.6% at first screen, and 1.8% later on. However, 90% of false positives were sorted out already at assessment. The percentage of screen detected invasive breast cancers with a tumour diameter < or = 10 mm was 39% compared with 16% of all invasive breast cancers in these age groups in Copenhagen before screening. CONCLUSION: Copenhagen is an area with a high incidence of breast cancer and with relatively little opportunistic screening. The start of a screening programme with a high recall rate in this area resulted in a detection rate above 1%. The Copenhagen programme met or exceeded most of the interim measures recommended in the European Guidelines.

Aged↗
PubMed2001

Collagenase-3 expression in breast myofibroblasts as a molecular marker of transition of ductal carcinoma in situ lesions to invasive ductal carcinomas.

Collagenase-3 (matrix metalloproteinase 13; MMP-13), a protease originally identified in breast carcinoma, is characterized by a potent degrading activity against a wide spectrum of extracellular matrix proteins. The aims of this study were to localize and identify the MMP-13-expressing cells in invasive human breast carcinoma and to evaluate the role of MMP-13 in transition to invasive lesions by studying ductal carcinoma in situ (DCIS). We found expression of MMP-13 in stromal fibroblast-like cells in all 21 invasive ductal carcinomas studied and in 4 of 9 invasive lobular carcinomas. In most carcinomas, expression of MMP-13 was limited to small stromal foci in the tumor area. Combined in situ hybridization and immunohistochemistry showed coexpression of alpha-smooth muscle actin immunoreactivity and MMP-13 mRNA in myofibroblasts. In contrast, cytokeratin-positive cancer cells, alpha-smooth muscle actin-positive vascular smooth muscle cells, CD68-positive macrophages, and CD31-positive endothelial cells were all MMP-13 mRNA negative. In situ hybridization for MMP-13 in 17 DCIS lesions revealed expression in 10 cases. Immunohistochemical analysis of all DCIS cases identified microinvasion in 8 of the 17 lesions. Seven of the eight lesions with microinvasion were MMP-13 positive. Further analysis showed that MMP-13 expression was often associated with the microinvasive events. This particular expression pattern was unique for MMP-13 among other MMPs analyzed, including MMP-2, -11, and -14. We conclude that MMP-13 is primarily expressed by myofibroblasts in human breast carcinoma and that expression in DCIS lesions often is associated with microinvasive events. On the basis of these data, we propose that MMP-13 may play an essential role during transition of DCIS lesions to invasive ductal carcinomas.

Biomarkers, Tumor↗
PubMed2001

Organochlorine exposures influence on breast cancer risk and survival according to estrogen receptor status: a Danish cohort-nested case-control study.

BACKGROUND: The relationship between breast cancer and organochlorine exposure is controversial and complex. As estrogen receptor positive and negative breast cancer may represent different entities of the disease, this study was undertaken to evaluate organochlorines influence on breast cancer risk and survival according to receptor status. METHODS: The background material stems from the Copenhagen City Heart Study (Denmark 1976-78). The breast cancer risk was investigated in a cohort nested case-control design including 161 cases and twice as many breast cancer free controls. The cases served as a cohort in the survival analysis. Serum organochlorine concentrations were determined by gaschromotography. RESULTS: The observed increased breast cancer risk associated with exposure to dieldrin derived from women who developed an estrogen receptor negative (ERN) tumor (Odds ratio [OR] I vs. IV quartile, 7.6, 95% confidence interval [95% CI] 1.4-46.1, p-value for linear trend 0.01). Tumors in women with the highest dieldrin serum level were larger and more often spread at the time of diagnosis than ERP tumors. The risk of dying was for the remaining evaluated compounds higher among patients with ERP breast cancer when compared to those with ERN. In the highest quartile of polychlorinated biphenyls (SigmaPCB) it was more than 2-fold increased (Relative risk [RR] I vs. IV quartile, 2.5, 95% CI 1.1-5.7), but no dose-response relation was apparent. CONCLUSION: The results do not suggest that exposure to potential estrogenic organochlorines leads to development of an ERP breast cancer. A possible adverse effect on prognosis of hormone-responsive breast cancers needs to be clarified.

Adult↗
PubMed2001

Urokinase plasminogen activator is localized in stromal cells in ductal breast cancer.

Urokinase plasminogen activator (uPA) regulates a proteolytic cascade that facilitates cancer invasion through degradation of the extracellular matrix, and high levels of uPA in human breast cancer tissue correlate with poor prognosis. We previously found that, in ductal breast cancer, uPA mRNA is highly expressed by myofibroblasts surrounding invasively growing cancer cells. However, the localization of uPA protein has not been settled in the published literature. Because uPA is a secreted molecule, it could conceivably be localized differently from its mRNA. We have studied the localization of uPA immunoreactivity in detail. Twenty-five cases of invasive ductal carcinoma were analyzed with three different uPA antibody preparations, all of which gave an essentially identical stromal staining pattern. Using double immunofluorescence, we identified uPA immunoreactivity in myofibroblasts and macrophages in all cases examined. Additionally, in approximately half of the tumors, we saw uPA staining of endothelial cells. In 3 of the 25 cases, a small subpopulation of the cancer cells was uPA-positive. We conclude that uPA immunoreactivity is almost exclusively associated with stromal cells, which thus play a major role in generation of proteolytic activity in ductal breast cancer.

Antibody Specificity↗
PubMed2000

Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast. European Commission Working Group on Breast Screening Pathology.

It is now widely recognised that classifying ductal carcinoma in situ (DCIS) of the breast and diagnosing atypical ductal hyperplasia are associated with significant interobserver variation. Two possible reasons for this inconsistency are differences in the interpretation of specified histological features and field selection where morphology is heterogeneous. In order to investigate the relative contribution of these two factors to inconsistent interpretation of intraductal proliferations, histological sections of 32 lesions were sent to 23 European pathologists followed 3 years later by images of small parts of these sections. Kappa statistics for diagnosing hyperplasia of usual type, atypical ductal hyperplasia and ductal carcinoma in situ were 0.54, 0.35 and 0.78 for sections and 0.47, 0.29 and 0.78 for images, respectively, showing that most of the inconsistency is due to differences in morphological interpretation. Improvements can thus be expected only if diagnostic criteria or methodology are changed. In contrast, kappa for classifying DCIS by growth pattern was very low at 0.23 for sections and better at 0.47 for images, reflecting the widely recognised variation in the growth pattern of DCIS. Higher kappa statistics were obtained when any mention of an individual growth pattern was included in that category, thus allowing multiple categories per case; but kappa was still higher for images than sections. Classifying DCIS by nuclear grade gave kappa values of 0.36 for sections and 0.49 for images, indicating that intralesional heterogeneity has hitherto been underestimated as a cause of inconsistency in classifying DCIS by this method. More rigorous assessment of the proportions of the different nuclear grades present could lead to an improvement in consistency.

Breast↗
PubMed2000

Impact of axillary dissection on staging and regional control in breast tumors < or = 10 mm--the DBCG experience. The Danish Breast Cancer Cooperative Group (DBCG), Rigshisoutalet, Copenhagen, Denmark.

Data from 4771 patients with tumor diameters < or = 10 mm were analyzed. Results of surgery and pathoanatomical examinations indicated that nodal status was related to diameter, but not to number of nodes removed. More axillary metastases were found in group T1b tumors than in T1a. In 8% of tumors, at least 4 positive nodes were identified. Mean number of positive nodes was related to number of nodes removed, and when 10 or more nodes were removed a significantly lower axillary recurrence rate and better recurrence-free survival were demonstrated, confirming that axillary surgery has two goals: staging and regional disease control. Age, receptor status, grade and histological type, but not tumor location, were related to prognosis. In accordance with the classical prognostic factors, it was not possible to define a patient group where axillary surgery was superfluous. We conclude that proper staging and regional control renders a full axillary level I-II dissection necessary.

Adult↗
PubMed1999

Consistency achieved by 23 European pathologists from 12 countries in diagnosing breast disease and reporting prognostic features of carcinomas. European Commission Working Group on Breast Screening Pathology.

A detailed analysis of the consistency with which pathologists from 12 different European countries diagnose and classify breast disease was undertaken as part of the quality assurance programme of the European Breast Screening Pilot Network funded by the Europe against Cancer Programme. Altogether 107 cases were examined by 23 pathologists in 4 rounds. Kappa statistics for major diagnostic categories were: benign (not otherwise specified) 0.74, atypical ductal hyperplasia (ADH) 0.27, ductal carcinoma in situ (DCIS) 0.87 and invasive carcinoma 0.94. ADH was the majority diagnosis in only 2 cases but was diagnosed by at least 2 participants in another 14, in 9 of which the majority diagnosis was benign (explaining the relatively low kappa for this category). DCIS in 4 (all low nuclear grade) and invasive carcinoma (a solitary 1-mm focus) in 1. The histological features of these cases were extremely variable; although one feature that nearly all shared was the presence of cells with small, uniform, hyperchromatic nuclei and a high nucleo-cytoplasmic ratio. The majority diagnosis was DCIS in 33 cases; kappa for classifying by nuclear grade was 0.38 using three categories and 0.46 when only two (high and other) were used. When ADH was included with low nuclear grade DCIS there was only a slight improvement in kappa. Size measurement of DCIS was less consistent than that of invasive carcinoma. The majority diagnosis was invasive carcinoma in 57 cases, the size of the majority being 100% in 49. The remainder were either special subtypes (adenoid cystic, tubular, colloid, secretory, ductal/medullary) or possible microinvasive carcinomas. Subtyping was most consistent for mucinous (kappa, 0.92) and least consistent for medullary carcinomas (kappa, 0.56). Consistency of grading using the Nottingham method was moderate (kappa=0.53) and consistency of diagnosing vascular invasion, fair (kappa=0.38). There was no tendency for consistency to improve from one round to the next, suggesting that further improvements are unlikely without changes in guidelines or methodology.

Breast Diseases↗
PubMed1998

Consistency achieved by 23 European pathologists in categorizing ductal carcinoma in situ of the breast using five classifications. European Commission Working Group on Breast Screening Pathology.

The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening, the greater use of breast-conserving surgery, and the recognition that certain histological subtypes are associated with a greater risk of local recurrence has led to the formulation of several new classifications of DCIS in recent years. There are, however, no data concerning the degree of consistency with which these schemes can be applied by reasonable numbers of pathologists. Thirty-three cases of DCIS were thus examined by a working group of 23 European pathologists who categorized them using five recently published classifications: (1) that of the European Pathologists' Working Group based on differentiation (a combination of nuclear grade and cell polarization) with categories of poorly, intermediately, and well differentiated; (2) one based entirely on nuclear grade with categories of high, intermediate, and low, currently in use in the UK national and EC-funded breast screening programs; (3) the same classification in which only two categories, high nuclear grade and other, were used; (4) the Van Nuys system in which lesions are divided into high grade, non-high grade with necrosis and non-high grade without necrosis; and (5) a two-category classification based entirely on the presence or absence of comedo necrosis. Of the three systems with three categories, Van Nuys gave the highest overall kappa statistic of 0.42. Others gave similar values of 0.37 and 0.35 showing that assessing cell polarization in addition to nuclear grade neither improves nor worsens consistency. In all three systems, the middle category was associated with the lowest value for kappa. Of the two systems with two categories, that based on nuclear grade gave the highest overall kappa of 0.46 and that based on comedo necrosis the lowest of 0.34. The most robust histological features were thus high- and low-grade nuclei and necrosis as long as the latter did not involve the recognition of a comedo growth pattern. These values probably represent the maximum achievable, at least by reasonable numbers of pathologists in everyday practice. They are better than those previously reported for classification based entirely on architecture, but further improvement is needed.

Breast Neoplasms↗
PubMed1995

Urokinase receptor in breast cancer tissue extracts. Enzyme-linked immunosorbent assay with a combination of mono- and polyclonal antibodies.

Urokinase plasminogen activator (uPA) is a proteolytic enzyme involved in degradation of the extracellular matrix during cancer invasion. The levels of uPA and its inhibitor PAI-1 in tumor extracts have previously been demonstrated to be of prognostic value in breast cancer as well as other types of cancer. We have previously characterized a specific cell surface receptor for uPA (uPAR) which strongly enhances the catalytic activity of uPA and is expressed during mammary cancer invasion. In order to quantitate uPAR in breast cancer tissue, we have now developed a sensitive enzyme-linked immunosorbent assay (ELISA), with polyclonal catching antibodies and three monoclonal detecting antibodies. The detection limit of the assay is approximately 0.16 fmol of uPAR in a volume of 100 microliters (1.6 pM). There is a linear relationship between signal and uPAR concentration up to at least 6.6 fmol per 100 microliters (66 pM). Both free uPAR and uPAR in complex with uPA is detected. The recovery of an internal uPAR standard in breast cancer tissue extracts is above 87%. The intra-assay and inter-assay variation coefficients are 7% and 13%. In order to find a suitable buffer for extraction of various components of the uPA-system from breast cancer tissue, we tested buffers which previously have been used for optimal extraction of estrogen receptor (A), uPA (B), and uPAR (C). Buffer A and B extracted approximately 30% and 50%, respectively, of the amount of uPAR extracted with buffer C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Primary prognostic factors in invasive breast cancer with special reference to ductal carcinoma and histologic malignancy grade.

BACKGROUND: In a study of 2290 cases of invasive breast cancer in Malmö, the prognostic value of histologic typing and axillary nodal status was examined. Two periods were studied: Period 1, 1961-1970, and Period 2, 1981-1988. METHODS: All primarily unilateral invasive breast cancers were included in the study and classified according to the histologic classification proposed by Linell et al. and Linell and Ljungberg (the Linell-Ljungberg classification), which includes a histologic grading of ductal carcinoma based on content of tubular structures. From Period 1, the tumors were reclassified. In Period 2, the Linell-Ljungberg classification was used as a clinical routine. Median follow-up in Period 1 was 23 years, and in Period 2, 5 years. Survival was calculated in relation to histologic type and axillary nodal status. RESULTS: The Linell-Ljungberg classification divides invasive ductal carcinoma (IDC) into two groups of approximately equal size: IDC of comedo type, 40% of total; and IDC of tubuloductal type, 30% of total. There was a significantly better survival rate in the tubuloductal group than in the comedo group. In a multivariate analysis, this difference was shown to be independent of axillary nodal status and tumor size. By combining histologic classification with axillary nodal status, one group of patients could be identified containing 90% of patients dying from breast cancer within 5 years of diagnosis and another group with less than 10% risk of dying from breast cancer within 5 years. CONCLUSIONS: Valuable prognostic information can be obtained in a clinical setting from routinely obtained primary prognostic factors in breast cancer: pTNM stage, histologic type, and histologic malignancy grade. This information should be considered the baseline in the clinical evaluation of other more elaborate prognostic factors.

Adult↗
PubMed1993

Five-year follow up of patients with cervical intra-epithelial neoplasia in the cone margins after conization.

Three hundred eighty-five women treated with conization due to repeated CIN I, CIN II or CIN III of the cervix uteri have been followed up for 5 years. All cones were classified according to diagnosis and status of the resection margins. A significantly greater recurrence rate of 16.2% was found in the group with neoplasia in the resection margins, in contrast to 3.9% in the group with normal resection margins. However, 83.8% (75.4-92.2%) of patients with neoplasia in the resection margins can be expected to be free of recurrence after a 5-year postoperative follow-up period. Whether the non-free resection margins were endocervical, ectocervical or both, did not influence the recurrence rate. While the prevalence of non-free resection margins increased significantly with increasing dysplasia, this could not be found with increasing age. The risk of recurrence could not be correlated with the grade of dysplasia. We conclude that neoplasia in the resection margins of the cone represents an increased risk of recurrence. Therefore, we changed the normal smear check-up with a cotton-swab to smear with cyto-brush, supplemented with colposcopy in the non-free resection margin group, but it remains to be proven that this procedure is safer.

Carcinoma in Situ↗