Biomedical subjects

L Dressler

Publications and source records attributed to L Dressler.

At least 19 recordsLinked to original sources

PubMed2001

Tumor characteristics in African American and white women.

BACKGROUND: Previous studies provide evidence that breast cancers occurring in different age and ethnic groups are not evenly distributed with regard to their biologic, pathologic and clinical characteristics. We evaluated the distributions of 11 pathological and biological variables between African-American (AA) and white patients and between three different age groups (20-39, 40-59 and 60-74 years). We examined whether racial differences existed across levels of age. METHODS: Data were obtained from the Carolina Breast Cancer Study (CBCS), a population-based, case-control study of breast cancer in North Carolina. Eighty hundred and sixty one women with a first diagnosis of invasive breast cancer participated in Phase I of the CBCS. Diagnostic paraffin blocks were obtained from 807 cases. One representative block was scored for histologic type and grade (architectural, nuclear, mitotic and overall). Medical chart review yielded tumor size, lymph node status, distant metastases, stage, hormone receptor status (ER/PR) and DNA ploidy. RESULTS: Pathologically advanced tumors (large size, high grade, high stage, ER/PR negative) were significantly more common in young and AA women. Racial differences varied by age. Among younger, AAs and whites differed only with respect to ER/PR status, while among older women AAs and whites differed only with respect to stage at diagnosis. CONCLUSIONS: The results of this study confirm the presence of poorer prognosis breast cancer among AA and younger women. They also highlight the need for age and race to be considered together when evaluating pathologic and biologic characteristics of disease and when making inferences regarding tumor aggressiveness.

Adult↗

PubMed2000

HER-2/neu and p53 expression versus tamoxifen resistance in estrogen receptor-positive, node-positive breast cancer.

PURPOSE: An association between the overexpression of proto-oncogene HER-2/neu and resistance to tamoxifen in estrogen receptor (ER)-positive primary and metastatic breast cancer has been suggested. We examine a possible interaction between HER-2/neu or p53 expression and tamoxifen effectiveness in patients with ER-positive, node-positive disease treated with cyclophosphamide, doxorubicin, and fluorouracil in a large adjuvant chemotherapy trial (Cancer and Leukemia Group B [CALGB] 8541). Tamoxifen assignment was not randomized-physician discretion was used for premenopausal and postmenopausal women. Trial protocol then specified assignment to postmenopausal women with ER-positive tumors, although not all took tamoxifen. PATIENTS AND METHODS: CALGB 8541 assessed HER-2/neu expression in patients with ER-positive disease by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) and amplification by differential polymerase chain reaction (PCR). IHC assessed expression of p53. Univariate and multivariate proportional hazards models assessed tamoxifen-HER-2/neu status interactions and tamoxifen-p53 status interactions. RESULTS: HER-2/neu status was available for 651 patients with ER-positive disease; 650, 608, and 353 patients were assessed by IHC, PCR, and FISH, respectively. Approximately one half received tamoxifen. Reduction in risk of disease recurrence or death resulting from tamoxifen was approximately 37% (32% with overexpression and 39% with normal expression of HER-2/neu; n = 155 by IHC). The tamoxifen-HER-2/neu status interaction was not significant in multivariate analysis of all three HER-2/neu assessment methods. Tamoxifen-p53 interaction did not significantly predict outcome. CONCLUSION: Disease-free and overall survival benefit of tamoxifen in patients with ER-positive, node-positive breast cancer does not depend on HER-2/neu or p53 status. Our data suggest that neither HER-2/neu nor p53 expression should be used to determine assignment of tamoxifen.

Antineoplastic Agents, Hormonal↗

PubMed1998

Genetic testing for the BRCA1 gene and the need for protection from discrimination: an evolving legislative and social issue.

Genetic testing for the BRCA1 gene is available commercially and clinically. The information gained from this test impacts not only on the individual tested, but on family members as well. The test can offer an individual and their family the opportunity to gain valuable information about their risks of developing certain forms of inherited breast cancer and other inherited cancers. In addition to its emotional and psychological impact, this information is associated with significant social and economic issues. This includes the potential for denial, loss, or increased rates for health insurance as well as denial and loss of employment based on genetic test information. The risk for such discrimination can lead to fear of seeking testing and can discourage participation in and potential benefit from prevention, screening, and treatment programs. Therefore, misuse of this information carries significant risk for the individual being tested and for their family members. It is imperative that the potential benefits of genetic testing and genetic information be afforded to all without this risk and fear. In addition to protecting all individuals from genetic discrimination, there is a need to protect the confidentiality of genetic information and an individual's right to privacy. This article discusses protection currently available through legislation at the federal and state level, focusing on the experience in North Carolina in developing and passing a genetic antidiscrimination bill. Although progress has been made, troublesome issues still remain.

Journal Article↗

PubMed1996

Predictive value of flow cytometric analysis in DNA contents in patients with locally advanced head and neck carcinoma.

A retrospective study was performed on 61 eligible patients with stage III and IV (AJC/UICC Staging System) squamous carcinomas of the head and neck region who were treated with definitive radiotherapy with, or without, surgery. DNA contents were measured by flow cytometric analysis of archival paraffin blocks and were correlated with clinicopathological findings, tumour response and patient survival. Comparison of variables including treatment modality was performed for identification of significant prognostic factors. There were 28 diploid, 27 aneuploid tumours and the remaining six were questionable. All patients were followed-up for at least two years or until death. Aneuploid tumours had a significantly higher S-phase fraction (percentage S-phase) (p < 0.001). Neither ploidy nor percentage S-phase were found to have predictive value in tumour response or patient survival within the power of a sample size of 61. Twenty of the 27 (74 per cent) aneuploid tumours had a complete response (CR) whereas 19 out of 28 (68 per cent) diploid tumours achieved CR. Five-year survival by the Kaplan-Meier method was 33 per cent for both aneuploid and diploid tumours. However, nodal stage (N stage) was found to have significant predictive value in both tumour response and patient survival. The complete response for stage N0 patients was 96 per cent, N1 patients 61 per cent, N2 patients 60 per cent and 43 per cent for N3 patients (p < 0.002). Similarly, the five year survival for the N0 and N3 groups of patients was 53 per cent and 29 per cent respectively (p < 0.05).

Adult↗

PubMed1995

The need for epidemiologic studies of in-situ carcinoma of the breast.

The purpose of this paper is to present background information on carcinoma in situ (CIS) of the breast and to provide a theoretical framework for planning epidemiologic studies which may further our understanding of breast cancer. Two types of epidemiologic studies are needed which incorporate CIS of the breast: (i) case-control studies, in which in-situ lesions serve as disease outcomes (endpoints), and (ii) cohort studies and clinical trials, in which diagnosis of in-situ carcinoma serves as a starting point for patient treatment and follow-up. Case-control studies focusing on the causes of CIS have distinct advantages: if risk factors for cancer contribute to pathways involving some intermediate stages but not others (e.g. comedo-type but not non-comedo-type DCIS; LCIS versus DCIS), the use of precursor lesions may more clearly reveal risk factor associations than studies of invasive breast cancer alone; epidemiologic studies of precursor lesions are conducted closer in time to the exposures suspected to be causes and may reduce recall bias or other forms of misclassification; genetic alterations in early lesions are more likely to represent causal events in development of the malignant phenotype. Population-based case-control studies of CIS may thus prove useful in understanding breast cancer etiology and designing preventive strategies. CIS patients identified for case-control studies may be followed up over time as a cohort. Cohort studies (and clinical trials) of CIS aim to elucidate mechanisms influencing progression of CIS to invasive cancer as well as to evaluate effectiveness of specific treatment modalities. Although the majority of CIS lesions of the breast are ductal carcinoma in situ (DCIS), epidemiologic studies which also include patients with lobular carcinoma in situ (LCIS) address potential differences between DCIS and LCIS with respect to both etiology and progression.

Breast Neoplasms↗

PubMed1994

Prognostic factors in early breast carcinoma.

Several investigators, the SEER data, and the ECOG/Intergroup study have shown that patients with small tumors (< 0.5 cm) have a recurrence rate of less than 2%, compared to 20-25% for large tumors (> or = 5 cm). Nuclear grade and tumor differentiation are established indicators; however, the interobserver lack of concordance has thwarted their use in clinical trials. The presence of peritumoral lymphatic and blood vessel invasion (PLBI) is associated with a relative risk of recurrence of 4.7. The predictive value of the presence of hormone receptors in tumors is associated with a favorable disease free and overall survival difference of 8-10%; however, this advantage is being eroded by the early appearance of other factors, such as the epidermal growth factor receptor (EGFR), proliferative capacity (S-phase), nuclear grade, and HER-2/neu oncogene. Concordance among the different methods of hormone-receptor assay (immunocytochemical, sucrose gradient, and dextran-coated charcoal) is essential to refine the true value of these factors. DNA flow cytometry measurements of ploidy (DNA content) and S-phase fraction are the most characterized of the prognostic factors. There are conflicting reports regarding the clinical significance of ploidy status, while measurements of S-phase fraction clearly indicate a robust association with disease free and overall survival. Our data continue to show that S-phase, but not ploidy, can predict time to recurrence significantly in untreated patients, even when data are stratified for tumor size. HER-2/neu oncogene is expressed in about 50% of ductal carcinoma in situ and 14% of invasive ductal carcinoma. The presence of this oncogene at high copy number may be a useful independent marker of poor prognosis and may be associated with drug resistance and correlated with tumor recurrence and shorter survival. EGFR could be measured in most breast tumors, and the level of its expression has inversely correlated with estrogen receptor protein expression. The value of EGFR as a predictor of prognosis remains controversial and is still being investigated. Cathepsin-D provides a provocative biologic rationale but is hindered by different and incongruent methods of analysis. The majority of large studies with more than 3-years' follow-up suggests that high cathepsin-D levels may be predictive of greater recurrence and lower survival. Angiogenesis has been implicated as a critical component of the metastatic process. Early studies show that tumor angiogenesis is an independent and highly significant prognostic indicator, and its presence may suggest the selection of "anti-angiogenic therapy."(ABSTRACT TRUNCATED AT 400 WORDS)

Breast Neoplasms↗

PubMed1994

Signet ring cell adenocarcinoma of prostate.

Primary signet ring cell adenocarcinoma of the prostate is a rare malignancy with a total of 13 cases reported to date in the English literature. We report a very unusual case of signet ring adenocarcinoma of the prostate occurring in a patient who presented initially with irritative voiding symptoms and a bladder mass. Results of immunohistochemical, flow cytometric, and cytogenetic analyses of the tumor are presented.

Carcinoma, Signet Ring Cell↗

PubMed1993

Clinical behavior of acoustic tumors. A flow cytometric analysis.

OBJECTIVE: Recently, nonsurgical treatment of acoustic tumors has been advocated as an alternative to surgical resection. Because of the relatively short follow-up in reported series of radiation-treated acoustic tumors, the lack of growth of some tumors may merely reflect the variable biologic growth potential of these tumors and not the result of treatment. DNA flow cytometry has been used to predict biologic activity in other solid tumors. It is applied in this study to assess the variability of growth potential in a typical acoustic tumor population and to determine whether relationships exist between flow cytometric data and clinical characteristics of acoustic tumors. DESIGN: DNA flow cytometry techniques were used to evaluate formalin-fixed, paraffin-embedded tissue previously obtained from patients who were surgically treated for acoustic neuromas. Relationships between flow cytometry data and historical data were also statistically evaluated. SETTING: Tissue samples were from patients of a large private otologic practice. PATIENTS: Subjects were a convenience sample of 49 patients (26 female and 23 male) with a mean age of 59 years who had undergone surgical removal of an acoustic neuroma. None of the patients had other stigmata of neurofibromatosis or tumor recurrence. All tissue specimens were pathologically confirmed acoustic neurons, with a range in tumor size from 1 to 6 cm. MAIN OUTCOME MEASURES: The measures included DNA ploidy and S-phase fraction. Historical data included age, sex, size of tumor, presenting symptom, and symptom duration. RESULTS: All 49 tumors showed a diploid distribution, with S-phase values ranging from 1.07% to 20.74% (mean +/- SD, 6.30 +/- 4.24). The ploidy and S-phase data compare favorably with previously published data in which fresh tissue was used. There were no statistically significant relationships between S-phase value and historical data. CONCLUSIONS: The wide range of S-phase values is consistent with a large variation in tumor growth potential and suggests caution in interpreting the results of radiation treatment of acoustic tumors when follow-up relatively short.

Adult↗

PubMed1991

Clinical applications of cytometry: 5th annual meeting.

The 5th annual Clinical Applications of Cytometry meeting was held September 12-15, 1990 in charleston, SC. The theme which emerged repeatedly throughout the meeting was the need to take full advantage of the quantitative power of cytometry to provide the most useful clinically relevant diagnostic and prognostic information. Greater quantitative power is based on careful and reproducible standards and quality control. The same principles, albeit with somewhat different approaches, apply to cell surface immunofluorescence analysis, DNA measurements, and image cytometry assessments. Monoclonal antibody probes against oncogenes, others against lymphokines within the Golgi, and a novel fluorogenic substrate designed to quantitate the activity of a mitochondrial enzyme were exciting developments described at the meeting.

Autoimmune Diseases↗

PubMed1990

Aggressive jejunal lymphoma of large granular lymphocytes. Immunohistochemical, ultrastructural, molecular, and DNA content analysis.

An unusual large cell lymphoma of the proximal jejunum with large granular lymphocyte (LGL) morphologic characteristics and T-helper/inducer cell phenotype is described. Although the cells strongly expressed Leu-7 (HNK-1), studies with antibodies directed against the more specific natural killer (NK) antigens, CD16 (Leu-11) and Leu-19, were negative. Ultrastructural analysis of the neoplastic cells demonstrated substantial numbers of electron-dense granules and rare parallel tubular arrays. Clonal rearrangement of the T-cell receptor beta chain gene and germline configuration of the immunoglobulin heavy chain gene confirmed the T-cell origin of the neoplastic cells. This lymphoma pursued an aggressive clinical course, with rapid dissemination to the lungs and central nervous system. DNA content analysis indicated that a similar DNA aneuploid population was present in the jejunal primary and lung tissue at recurrence. There was no evidence of nodal, peripheral blood, splenic, or bone marrow involvement. Morphologic and functional similarities between the lymphoid tissues of the gastrointestinal tract and lung have previously prompted a classification of the immune system into distinct peripheral somatic and mucosal components. Based on the distribution and migratory properties of the tumor cells in this case, the authors propose that this lymphoma arose from a minor mucosa-associated LGL subset that may be unrelated to circulating LGLs. In addition, these observations emphasize that prominent granulated cytomorphologic features may be seen in neoplastic disorders with the T-helper/inducer phenotype, as well as in the more widely recognized lymphoproliferative disorders of NK and cytotoxic/suppressor cell types.

Aged↗

PubMed1989

High-grade non-Hodgkin lymphoma relapsing as low-grade follicular lymphoma: so-called downgraded lymphoma.

Evolution of low-grade Non-Hodgkin Lymphoma (NHL) into a more aggressive neoplasm is a common, well-documented event in NHL. The reverse process, in which a less aggressive component becomes evident during the course of treatment for a higher-grade NHL, has only recently been recognized. This lymphoma "downgrading" has been reported at the time of relapse in both radiation- and chemotherapy-treated patients who initially presented with high- or intermediate-grade lymphoma. The etiology of this unusual transformation has not yet been determined. We present the clinical, morphologic, immunologic, and flow-cytometric features of a patient with diffuse immunoblastic lymphoma who achieved a complete response to chemotherapy and then relapsed with follicular small-cleaved-cell lymphoma 3 years later. Morphologic and immunophenotypic findings suggest that both immunoblasts and small cleaved cells were present in the initial biopsy. DNA content analysis of the initial and relapse biopsies suggests that the immunoblastic component was more susceptible than the small cleaved cells to the chemotherapy that the patient received. Successful eradication of the rapidly proliferating immunoblasts with survival of less rapidly proliferating small cleaved cells may account for the unusual histologic transformation seen in this case.

Adult↗

PubMed1989

Hematogones: a multiparameter analysis of bone marrow precursor cells.

Morphologically distinct lymphoid cells with homogeneous, condensed chromatin and scant cytoplasm can be observed in large numbers in the bone marrow of children with a variety of hematologic and nonhematologic disorders. In some patients, these cells may account for greater than 50% of the bone marrow cells, creating a picture that can be confused with acute lymphoblastic leukemia (ALL) or metastatic tumor. Although originally called hematogones (HGs), a variety of other names have been proposed for these unique cells. The clinical significance of expanded HGs has not been resolved, and the biologic features of these cells are incompletely described. In this study, we correlate the clinical, morphologic, cytochemical, flow cytometric, molecular, and cytogenetic properties of bone marrow samples from 12 children with substantial numbers of HGs (range 8% to 55% of bone marrow cells). Diagnoses in these patients included anemia, four; neutropenia, one; anemia and neutropenia, one; idiopathic thrombocytopenic purpura, two; retinoblastoma, two; Ewing's sarcoma, one; and germ cell tumor, one. Flow cytometric analyses of bone marrow cells demonstrated a spectrum extending from early B-cell precursors (CD10+, CD19+, TdT+, HLA-Dr+) to mature surface immunoglobulin-bearing B cells in these patients, corroborating our morphologic impression of HGs, intermediate forms, and mature lymphocytes. DNA content was normal, and no clonal abnormality was identified by either cytogenetic or immunoglobulin and T-cell receptor (TCR) gene rearrangement studies. Follow-up ranged from 3 months to 3 years. None of the patients has developed acute leukemia or bone marrow involvement by solid tumor. The possible role of HGs in immune recovery and hematopoiesis is presented.

Biomarkers, Tumor↗

PubMed1985

[Heart valve replacement with myocardial revascularization].

Coexisting coronary artery insufficiency includes risks to patients with valvular heart disease, thus complicating management. In 15 patients requiring aortic or mitral valve replacement preoperative coronary angiography demonstrated severe coronary stenoses which were treated by bypass grafts with valve surgery. These combined operations turned out to be safe and effective.

Adult↗

PubMed1979

The optimization of the pulse delivered by the pacemaker.

The results of stimulation threshold analysis carried out in 230 patients after the initial electrode implantation, and in 188 patients during pacemaker replacement, are presented. The electrodes investigated were the IE-60K-10 (279 cases), the IE-60-K (96 cases) and the ME-50 (26 cases). The chronic stimulation threshold voltage for the electrode IE-60K-10 (electrode surface area: 10 mm2) at a pulse width of 0.5 ms, after an electrode function time of 25 months, is 2.05 +/- 0.18 V, representing 256% of the acute threshold, and is equally as high as the chronic figure for the IE-60-K electrode (surface area: 27 mm2) measured at 2.08 +/- 0.20 V. The current threshold for the IE-60K-10 increased from 0.78 +/- 0.07 mA by 299% to 2.33 +/- 0.30 mA and was thus, as expected, lower than that of the large area electrode IE-60-K, which increased from 1.11 +/- 0.22 mA to 3.23 +/- 0.43 mA (291%). On the basis of the computation of the stimulation threshold energy and the stimulation threshold charge, a reduction of pulse duration to below 0.5 ms would not appear to make such energy-saving sense.

Electrodes, Implanted↗

PubMed1975