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L J Layfield

Publications and source records attributed to L J Layfield.

At least 55 records · Page 3Linked to original sources
PubMed1998

Association between ratio of matrix metalloproteinase-1 to tissue inhibitor of metalloproteinase-1 and local recurrence, metastasis, and survival in human chondrosarcoma.

Chondrosarcoma, a malignant cartilage-forming mesenchymal tumor, displays a wide range of clinical behavior that can be difficult to predict with histological analysis. Matrix metalloproteinases contribute to the processes of local invasion and metastasis by controlling the ability of a tumor to transverse tissue boundaries. The specificity of matrix metalloproteinase-1 (interstitial collagenase) for fibrillar collagen may be central to those processes. Matrix metalloproteinase-2 facilitates invasion by degradation of such basement-membrane structures as type-IV collagen. The balance between the activity of tissue inhibitors of metalloproteinase and the activity of matrix metalloproteinase determines the proteolytic activity and may, in part, determine the overall invasiveness and potential for metastasis. The measurement of the ratio of matrix metalloproteinase to tissue inhibitor of metalloproteinase may have prognostic value for determining whether individual chondrosarcomas are locally invasive or will metastasize. Furthermore, there may be a specific pattern of expression of matrix metalloproteinase and tissue inhibitor of metalloproteinase in chondrosarcomas that is related to local invasion and probability of metastasis. Sixteen paraffin-embedded archival specimens of tumors were examined. Six twenty-micrometer-thick sections were cut from each tumor, and the amounts of cDNA formed from the mRNA were determined with reverse transcription-polymerase chain reaction with use of novel primers for matrix metalloproteinase-1, matrix metalloproteinase-2, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2. The amounts of cDNA for the matrix metalloproteinases and their inhibitors were determined by chemiluminescence and band densitometry. The ratio of the amount of cDNA for matrix metalloproteinase-1 to that for its tissue inhibitor and the ratio of the amount of cDNA for matrix metalloproteinase-2 to that for its tissue inhibitor were calculated, and the results were compared with use of the Student t test, enabling log-rank analysis of Kaplan-Meier survival curves. These ratios as well as the age and gender of the patient; the grade, size, and location of the tumor; the type of adjuvant therapy; and the operative margins were examined for significance with use of stepwise logistic-regression analysis. The patients who had recurrent disease had a significantly higher (p < 0.003) ratio of matrix metalloproteinase-1 to tissue inhibitor of metalloproteinase-1 (mean, 0.939; range, 0.647 to 1.101) than the patients who were free of disease (mean, 0.703; range, 0.629 to 0.772). Moreover, there was a striking difference between the Kaplan-Meier survival curve associated with a high ratio (more than 0.8) and that associated with a low ratio (p = 0.0015). The mean ratio of matrix metalloproteinase-2 to tissue inhibitor of metalloproteinase-2 was 1.814 (range, 1.206 to 3.77) in the patients who had recurrent disease compared with 1.473 (range, 1.073 to 2.390) in those who were free of disease; this difference was not found to be significant, with the numbers available. Analysis of the survival curves indicated that a worse prognosis was associated with a high ratio, but again this relationship was not found to be significant. Regression analysis revealed that a high ratio of matrix metalloproteinase-1 to its tissue inhibitor was a moderately significant independent predictor of a poor outcome (alpha = 0.07).

Adult↗
PubMed1997

What constitutes an adequate smear in fine-needle aspiration cytology of the breast?

BACKGROUND: The false-negative diagnosis is a major clinical concern and a significant cause of litigation in fine-needle aspiration cytology of breast lesions. A significant number of false-negative diagnoses may be due to inadequate sampling of these lesions. Little information is available in the literature about what constitutes an adequate specimen, and the few publications that address this issue propose criteria based on anecdotal information. Recommendations vary widely and may or may not take clinical findings into account. METHODS: The authors studied a subgroup of 183 cases with known outcome, drawn from a series of 1779 cases, to determine the minimum number of cell clusters necessary to ensure that adequate cellular material was present for accurate diagnosis. The series included 21 cases cytologically diagnosed as false-negative, 75 cases that had been correctly identified as benign, 47 cases cytologically designated as atypical, and 40 cases that on initial review had been correctly identified as malignant. In semiblind fashion, the smears from each case were assigned to low, medium, and high cellularity categories. Low cellularity was defined as 10 or fewer cell clusters, moderate cellularity was defined as 11-30 clusters, and high cellularity was defined as more than 30 clusters. A cell cluster was defined as five or more cells. Within the low cellularity group, exact numbers of cell clusters and the presence of individual cells were recorded. The presence of bipolar cells was used as an adjunct criterion for specimen adequacy, and the bipolar cells in each of 10 x 200 fields were counted. Cellularity was then correlated with diagnostic accuracy. RESULTS: Using a cutpoint of a cumulative score of 6 or more cell clusters or the prominence of bipolar cells (> or = 10 in each of 10 medium-power, x200 fields) for assessment of specimen adequacy, a false-negative rate of 1.5%, associated with an unsatisfactory rate of 20.2%, was obtained. CONCLUSIONS: Based on the data gathered in this study, the authors believe that the sampling false-negative and unsatisfactory rates can be minimized by selecting a cutpoint for satisfactory smears at a level of 6 or more cell clusters (cumulative total) or the presence > or = 10 intact bipolar cells per 10 medium-power fields (x200). Use of these criteria will decrease the false-negative rate of sampling in epithelial lesions of the breast. A false-negative rate of approximately 1.5% was obtained in association with an unsatisfactory rate of 20.2%. Using a cutpoint of 1 or more cell clusters, a false-negative rate of 2.1%, associated with an unsatisfactory rate of 13.7%, was obtained.

Biopsy, Needle↗
PubMed1997

Intratumoral heterogeneity in primary breast carcinoma: study of concurrent parameters.

BACKGROUND AND OBJECTIVE: Intratumoral heterogeneity for prognostic factors (ploidy, proliferation, hormone receptor positivity) has been demonstrated in primary breast carcinoma by both flow cytometric and image analysis methods. Previously, heterogeneity in tumors had been demonstrated for only singular parameters. Our objective, using maps of tumors in which discrete regions can be analyzed simultaneously for DNA index (DI) and proliferative activity, was to demonstrate heterogeneity with respect to two parameters and to determine whether any interparametric relationships existed. METHODS: We analyzed 25 cases of archived, paraffin-embedded breast carcinoma (ductal) for Feulgen stain DNA analysis and MIB-1 immunohistochemistry using the CAS 200 Image Cytometer. For each tumor, four discrete regions were analyzed including tumor-host tissue interface sectors. RESULTS: Of 25 cases, 19 (76%) were homogeneously diploid or near-diploid aneuploid, and 6 (24%) were heterogeneous. Within the heterogeneous group, all cases had at least one diploid and one or more aneuploid populations from separate discrete regions. Five of six DI heterogeneous tumors displayed diploid values for the overall measurements of the respective tumors, based on analysis of 200 or more nuclei. Eight of 25 cases (32%) showed significant measurable variation for MIB-1 proliferative activity in various sectors of tumor. All the MIB-1 heterogeneous tumors, with one exception, were homogeneously diploid. CONCLUSIONS: These findings demonstrate that (1) heterogeneity is present with respect to DI and proliferative activity in breast carcinoma and is relatively common, (2) tumors homogeneous for one parameter may be heterogeneous for another, and (3) heterogeneity for proliferative activity is more common in homogeneously diploid tumors than in heterogeneous/aneuploid tumors.

Breast Neoplasms↗
PubMed1997

Prognostic factors for fibromatoses: a correlation of proliferation index, estrogen receptor, p53, retinoblastoma, and src gene products and clinical features with outcome.

BACKGROUND: The aggressiveness of fibromatoses is difficult to predict by morphologic analysis. Additional prognostic markers would be helpful for clinical management. MATERIALS AND METHODS: Proliferation index (MIB-1), p53, src, retinoblastoma gene protein products, estrogen receptor level, site and depth of lesion were correlated with incidence of recurrence in 52 patients. Superficial (47) and deep (5) fibromatoses were studied. Anatomic sites included the extremities, head, neck, trunk, and pelvis. RESULTS: Twenty (38%) lesions recurred locally. All five deep lesions recurred, but only 32% of superficial tumors recurred. Mean proliferation index for recurrent lesions was 0.82% and 0.73% for nonrecurrent fibromatoses; no significant differences were observed. Five recurrent lesions (25%) expressed estrogen receptor > 5 fmol/mg as did 31% (10 of 32) of the nonrecurrent lesions. None of the tested specimens expressed src gene product. Eight of the lesions which recurred (40%) contained p53, but only five nonrecurring tumors (16%) expressed p53. One of five deep lesions (20%) expressed p53 and 26% (12 of 47) of superficial tumors expressed p53. Forty-six percent (6 of 13) of recurrent lesions tested were retinoblastoma protein product negative, but only 33.3% (7 of 21) of nonrecurring tumors were retinoblastoma protein product negative. CONCLUSIONS: Only p53 and depth of lesion were of statistical value for the prediction of recurrence.

Biomarkers, Tumor↗
PubMed1997

Prognostic value of MIB-1 in advanced ovarian carcinoma as determined using automated immunohistochemistry and quantitative image analysis.

BACKGROUND AND OBJECTIVES: The monoclonal antibody MIB-1 is an immunohistochemical marker reacting most strongly with cells in late S phase, G2, and M portions of the cell cycle. This antibody, reactive in formalin-fixed, paraffin-embedded tissue, allows the quantitation of a proliferation index (PI) in both current clinical cases and archival material using a computerized image analyzer (CIA). METHODS: Since many laboratories make use of automated immunohistochemistry (AIH), this study was performed to explore the technical feasibility of using AIH (Ventana ES 320) in combination with CIA (CAS 200) to evaluate MIB-1 PI as a prognostic marker as assessed by overall survival in 50 archival (formalin-fixed, paraffin-embedded), advanced stage primary ovarian carcinomas. RESULTS: Exploratory methods confirmed that 15% was a cutpoint that could dichotomize these 50 patients into two prognostic groups based on overall survival. The median survival of patients whose carcinoma had a high MIB-1 expression (> or = 15%) was 16 months compared with 30 months in the patients whose tumors demonstrated low MIB-1 expression (< 15%, P = 0.01). After adjustment for age, MIB-1 retained its prognostic significance (P = 0.02). Patients 60 years and older had shorter survival than younger patients (P = 0.06), but these two groups did not differ with respect to PI (P = 0.76). Those patients with a negative second look laparotomy had a longer median survival of 70 months compared with 18.5 months in patients with a positive second look (P < 0.001); the median PIs were 17% and 27%, respectively (P = 0.36). There were no significant relationships between clinical stage, nuclear grade, DNA ploidy, p53, and either survival or PI. CONCLUSIONS: In this study, we concluded that the combination of AIH and CIA yielded a reliable quantitation of MIB-1 proliferative index and that this proliferative marker had prognostic significance in late stage ovarian carcinoma. Further studies in a larger group of patients are needed to confirm the relationship between proliferation index and other known clinicopathologic and genetic variables.

Antibodies, Monoclonal↗
PubMed1997

Cytologic findings in tenosynovial giant cell tumors investigated by fine-needle aspiration cytology.

Tenosynovial giant cell tumor is a relatively common benign proliferation affecting the articular and periarticular soft tissues. Cytologic findings on smears obtained by fine-needle aspiration are rather characteristic and include a mixture of oval or polygonal mononuclear cells showing vacuolation and/or pigment deposition along with a population of multinucleated giant cells. Separation from other giant cell lesions including true giant cell tumor of bone, chondroblastoma, aneurysmal bone cyst, and granulomatous inflammation must be made. Careful attention to the cytologic findings and correlation with clinical and radiographic data should result in the appropriate diagnosis of tenosynovial giant cell tumor in most cases.

Adult↗
PubMed1997

Cytologic features of pulmonary metastasis from a granulosa cell tumor diagnosed by fine-needle aspiration: a case report.

We report on a case of a granulosa cell tumor of the ovary metastatic to the lung and diagnosed by fine-needle aspiration. The patient was a 70-yr-old woman who was diagnosed with a granulosa cell tumor of the ovary 17 yr previously. She subsequently developed abdominal metastases and received several cycles of chemotherapy. A 0.5-cm right upper lobe pulmonary nodule was found on a routine chest radiograph and subsequent computerized tomography scan. Aspiration cytology of this pulmonary nodule demonstrated small, relatively uniform neoplastic cells with nuclear grooves and indentations consistent with a granulosa cell tumor. The differential diagnosis of granulosa cell tumors from other metastatic and pulmonary lesions is reviewed.

Aged↗
PubMed1997

Fine-needle aspiration cytology findings in a case of aggressive angiomyxoma: a case report and review of the literature.

Aggressive angiomyxomas are uncommon but distinct soft-tissue neoplasms occurring predominantly in the pelvis and peritoneum of females, but they have occasionally been reported in association with inguinal hernias in males. Histologically, these neoplasms are characterized by a proliferation of spindle- or stellate-shaped cells widely separated by loose myxoid stroma in which is dispersed a prominent vascular component. The vascular component is comprised of large, thick-walled vessels that generally to not show an arborizing pattern. Mitotic activity has been exceedingly low in the cases reported. Because of their occurrence within the groin, these lesions may undergo fine-needle aspiration (FNA). Cytologic examination of this material will reveal hypocellular smears containing scattered spindle cells with bipolar cytoplasmic processes, as well as bland stellate cells. The nuclei are fusiform to oval with a bland chromatin pattern. The stromal cells lie in a background of watery myxoid material. While specific diagnosis by FNA is not possible, the recognition of this cytologic appearance should exclude lymphoproliferative processes as well as metastatic disease from the differential diagnosis. Careful attention to cytologic detail should also help exclude certain other myxoid neoplasms, especially myxoid liposarcoma. Once the myxoid stromal nature of the proliferation is recognized, a differential diagnosis of myxoid lesions can be considered along with a recommendation for open biopsy to establish the definitive diagnosis.

Adult↗
PubMed1997

Fine-needle aspiration biopsy of salivary duct carcinoma: report of five cases.

Salivary duct carcinoma is a high grade malignancy which histologically strongly resembles ductal carcinoma of the breast. The findings from five cases of histologically proven salivary duct carcinoma sampled by preoperative fine-needle aspiration (FNA) cytology are presented. Characteristic cytomorphologic features include cohesive clusters and flat sheets of epithelial cells which display a cribriform pattern with eccentrically located, hyperchromatic nuclei, abundant finely granular cytoplasm, and necrosis in the smear background.

Aged↗
PubMed1997

Salivary gland lesions with a prominent lymphoid component: cytologic findings and differential diagnosis by fine-needle aspiration biopsy.

Fine-needle aspiration (FNA) is an accepted technique for the preoperative diagnosis of salivary gland nodules. The majority of salivary gland nodules are pleomorphic adenomas and offer little difficulty in diagnosis. Most diagnostically difficult lesions fall into one of four morphologic categories represented by squamous-cell-containing lesions, clear cell neoplasms, neoplasms with a prominence of stromal material, and lymphocyte-containing lesions. Herein, we describe our experience with a series of 61 histologically confirmed cases in which the smears contained a prominent or predominant number of lymphocytes. The differential diagnosis is discussed and points of diagnostic aid enumerated.

Adenolymphoma↗
PubMed1997

Fine-needle aspiration of epithelioid malignant peripheral nerve sheath tumor (epithelioid malignant schwannoma).

The epithelioid variant of malignant peripheral nerve sheath tumor (MPNST), also known as malignant epithelioid schwannoma, is a relatively rare and recently characterized clinicopathologic entity. The epithelioid variant of MPNST shares many clinical features with conventional MPNST but is characterized by different histologic and cytologic features. These include a distinctive nesting pattern and an abundance of cytoplasm not seen in histology of conventional nerve sheath tumors. Cytologically, the epitheliod variant shows a propensity to cellular discohesiveness and a plasmacytoid or epitheliod appearance that is in contradistinction to the spindled appearance of the usual MPNST. Herein, we report our experience with fine-needle aspiration (FNA) of two epithelioid malignant schwannomas and discuss the FNA cytologic differential diagnosis.

Adult↗
PubMed1997

Intramammary lymph nodes: cytologic findings and implications for fine-needle aspiration cytology diagnosis of breast nodules.

The recognition of intramammary lymphoid proliferations is important because smears of these proliferations would be judged as insufficient by several of the published criteria for specimen adequacy. Alternatively, some might be confused with medullary carcinoma of the breast or adenocarcinomas with a "single-cell" pattern. We found 19 intramammary lymphoid proliferations in a series of 887 fine-needle aspirates of palpable breast nodules. Six were lymphomas and 13 were benign intramammary lymph nodes. Smear cellularity ranged from scant to high, but in all cases, lymphocytes dominated the cell population. The cytology of intramammary lymph nodes and lymphoma did not differ from those occurring at other sites.

Adult↗
PubMed1997

Proliferative index determination in prostatic carcinoma tissue: is there any additional prognostic value greater than that of Gleason score, ploidy and pathological stage?

PURPOSE: The proliferative index was evaluated as an additional prognostic variable in 244 radical prostatectomy specimens from patients with prostate cancer. This study was done on the grounds that this variable has shown some promise as a prognostic tool in some other carcinomas, for example breast cancer. MATERIALS AND METHODS: The proliferative index was evaluated in 244 patients undergoing radical prostatectomy for clinically localized disease between January 1988 and August 1994. Proliferative index was determined using the Ki-67 antibody on fresh frozen tissue and MIB-1 on paraffin embedded tissues. Patients were divided into 2 groups based on a proliferative index of less than 1 (185) or 1 or greater (59). Of the patients 49 (20%) had biochemical failure (median 23 months to progressive prostate specific antigen elevation of 0.5 ng./ml. or more). Those whose treatment failed were also divided into 2 groups according to proliferative index: 32 of 185 (18%) with an index of less than 1 and 17 of 59 (27%) with an index of 1 or more. Gleason score and deoxyribonucleic acid ploidy status were also evaluated in all patients and compared in multivariate regression analysis. Operative specimens were categorized as organ confined, specimen confined or margin positive. RESULTS: The distribution according to margin status in the 2 groups (proliferative index less than 1 and 1 or more) was 40 versus 60% for organ confined, 67 versus 33% for specimen confined and 72 versus 28% for margin positive disease, respectively. The distribution of time to treatment failure in the 2 groups was not markedly different: 7.2 versus 9.4 months for margin positive, 10 versus 14.5 months for specimen confined and 8.5 versus 12 months for organ confined cancer, respectively. CONCLUSIONS: Multivariate analysis demonstrated that, although deoxyribonucleic acid ploidy seemed to correlate with more advanced disease, only Gleason sum and pathological T stage reached statistical significance when evaluated against time to treatment failure. A high proliferative index added little above the more traditional prognostic indicators of Gleason score, pathological stage and ploidy. Therefore, we question the value of proliferative index as a prognostic indicator using the aforementioned methodology in prostate cancer.

Adult↗
PubMed1997

Fine-needle aspiration of the liver and pancreas: a cytology primer for radiologists.

Fine-needle aspiration (FNA) is increasing in popularity as a means of diagnosing mass lesions in intraabdominal organs. With use of radiologic guidance for needle placement, this technique is an effective way to obtain diagnostic material. In selected instances, FNA is superior to core-needle or open biopsy in terms of cost, procedure-associated morbidity, and timeliness of diagnosis. This article summarizes the cytologic features of hepatic and pancreatic lesions most likely to be seen in an active interventional radiologic practice. The specific cytopathologic findings of the more common lesions are emphasized. The authors also discuss some of the limitations of FNA and how to optimize the procurement and utilization of specimen material to obtain the best possible diagnostic outcome.

Biopsy, Needle↗
PubMed1996

Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas.

The adverse prognostic impact of tumor hypoxia has been demonstrated in human malignancy. We report the effects of radiotherapy and hyperthermia (HT) on soft tissue sarcoma oxygenation and the relationship between treatment-induced changes in oxygenation and clinical treatment outcome. Patients receiving preoperative radiotherapy and HT underwent tumor oxygenation measurement pretreatment after the start of radiation/pre-HT and one day after the first HT treatment. The magnitude of improvement in tumor oxygenation after the first HT fraction relative to pretreatment baseline was positively correlated with the amount of necrosis seen in the resection specimen. Patients with <90% resection specimen necrosis experienced longer disease-free survival than those with > or = 90% necrosis. Increasing levels of tumor hypoxia were also correlated with diminished metabolic status as measured by P-31 magnetic resonance spectroscopy.

Cell Hypoxia↗
PubMed1996

Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma.

This study was performed to explore the relationship between tumor oxygenation and treatment outcome in human soft tissue sarcoma. Twenty-two patients with nonmestastatic, high-grade, soft tissue sarcomas underwent preoperative irradiation and hyperthermia and pretreatment measurement of tumor oxygenation. The 18-month actuarial disease-free survival was 70% for patients with tumor median oxygen pressure (pO2) values of >10 mm Hg but only 35% for those with median pO2 values of <10 mm Hg (P=0.01). There were eight treatment failures; the first site of recurrence was lung in all patients. Median pO2 was 7.5 mm Hg for metastasizing tumors versus 20 mm Hg for nonmetastasizing tumors (P=0.03). Potential mechanisms and implications for clinical trial design are discussed.

Cell Hypoxia↗
PubMed1996

Estrogen and progesterone receptor status determined by the Ventana ES 320 automated immunohistochemical stainer and the CAS 200 image analyzer in 236 early-stage breast carcinomas: prognostic significance.

The quantitation of estrogen and progesterone receptors (ER and PgR) has become the standard of care in the evaluation of patients with primary breast carcinoma. It has been demonstrated that ER and PgR detected by immunohistochemical methods in formalin-fixed paraffin-embedded tissue can be quantified by computerized image analysis. In this study, ER and PgR levels were determined by using an automated immunochemistry stainer (Ventana ES 320) and an image analyzer (CAS 200) in a series of 236 patients with stage I/II carcinoma of the breast. The degree of correlation of the ER and PgR levels determined by the dextran-coated charcoal method (DCC) with image analysis quantitation was high (r=0.75). The agreement between both methods was 77% for ER and 73% for PgR. Hormone receptor levels were correlated with prognosis as determined by overall survival. An ER level of 30 fmol/mg as determined by image analysis was established to stratify the patient population most effectively into favorable and unfavorable prognostic groups (P=0.003). An ER level of 20 fmol/mg for prognostic stratification reached statistical significance (P=0.03). The DCC method was not able to stratify the patients into prognostic groups at the traditionally accepted cutpoint of 10 fmol/mg (P=0.52). We conclude that when used in combination, automated immunohistochemistry and quantitative image analysis offer a favorable alternative to the DCC method in assessment of ER and PgR status in human mammary carcinoma. In addition, quantitative immunocytochemistry techniques may prove superior to the DCC method in specimens in which there is limited tumor volume (including fine-needle aspirates), stroma-rich tumors, and early-stage lesions including intraductal carcinoma.

Aged↗