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D E Elder

Publications and source records attributed to D E Elder.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cytokeratin 15 expression in trichoepitheliomas and a subset of basal cell carcinomas suggests they originate from hair follicle stem cells.

Trichoepitheliomas and many basal cell carcinomas appear to arise from the hair follicle, and in particular from the hair follicle bulge. This histogenesis is suggested from both morphological and immunohistochemical studies on tumor cells and stroma. Epithelial stem cells are thought to be important in tumorigenesis, and we previously localized a population of stem cells to the bulge area of the outer root sheath. We recently identified an anti-CD8 monoclonal antibody (DAKO clone C8/144B) that cross-reacts with cytokeratin 15 (K15), and serves as a specific marker for the bulge. In this study, we screened a series of trichoepitheliomas (n=13), basal cell carcinomas (n=37) and a variety of other skin tumors with this antibody. All trichoepitheliomas (100%) showed keratin 15 expression, while only a subset of basal cell carcinomas (27%) was K15-positive. Epidermal tumors, including squamous cell carcinomas, were K15-negative. Tumors of follicular derivation such as proliferating trichilemmal cysts were also K15-positive, while others such as pilomatricoma were K15-negative. Expression of K15 in trichoepitheliomas, some basal cell carcinomas and other follicular tumors suggests that these tumors are related to hair follicle stem cells in the bulge.

Antibodies, Monoclonal↗
PubMed1999

99mTc-human serum albumin: an effective radiotracer for identifying sentinel lymph nodes in melanoma.

UNLABELLED: Sentinel lymph node (SLN) biopsy has emerged as a novel approach for identifying patients with melanoma and regional nodal micrometastasis who may benefit from full nodal basin resection. To identify the pattern of tumor lymphatic drainage and the SLN, lymphoscintigraphy has been performed using primarily 99mTc-sulfur colloid (SC). In this study, we compare the efficacy of SLN biopsy using 99mTc-human serum albumin (HSA) with SLN biopsy after SC-based lymphoscintigraphy. METHODS: One hundred and six patients with localized cutaneous melanoma were studied. Lymphoscintigraphy was performed after intradermal injection of HSA in 85 patients and SC in 21 patients. Four patients underwent lymphoscintigraphy twice, once with SC and once with HSA. Dynamic images were acquired for up to 1 h, followed by high-count images of the SLN in various projections so that the most likely site was marked on the skin for biopsy. Intraoperatively, blue dye was injected around the primary site. Twenty-four patients underwent SLN dissection directed by preoperative lymphoscintigraphy and vital blue dye mapping; in the remaining 80 patients, a gamma probe was added intraoperatively to the localization procedure. Two patients underwent mapping with gamma probe alone. RESULTS: Draining lymphatic basins and nodes were identified by lymphoscintigraphy in all patients. The SLN was identified in 95% of patients when both blue dye and intraoperative gamma probe were used. When 99mTc-HSA was used for imaging, 98% of the SLNs ultimately identified were radiolabeled, and 82% were both hot and blue. Of the SLN recovered with SC, all the nodes were radiolabeled; however, there was only 58% hot and blue concordance. Greater numbers of SLNs were removed in the SC group (median 2.0 versus 1.0, P = 0.02); however, the incidence of micrometastasis was statistically similar in both HSA and SC cohorts. In the 4 patients examined with both tracers, SLN mapping was similar. CONCLUSION: Although SC has been the radiotracer of choice for SLN mapping in melanoma, HSA appears to be a suitable alternative, with identical success rates. In fact, the higher concordance between hot and blue nodes using HSA suggests superiority of this tracer for this purpose.

Biopsy↗
PubMed1998

Adenoviral gene transfer of beta3 integrin subunit induces conversion from radial to vertical growth phase in primary human melanoma.

Expression of the beta3 subunit of the alphavbeta3 vitronectin receptor on melanoma cells is associated with tumor thickness and the ability to invade and metastasize. To address the role of alphavbeta3 in the complex process of progression from the nontumorigenic radial to the tumorigenic vertical growth phase of primary melanoma, we examined the biological consequences of overexpressing alphavbeta3 in early-stage melanoma cells using an adenoviral vector for gene transfer. Overexpression of functional alphavbeta3 in radial growth phase primary melanoma cells 1) promotes both anchorage-dependent and -independent growth, 2) initiates invasive growth from the epidermis into the dermis in three-dimensional skin reconstructs, 3) prevents apoptosis of invading cells, and 4) increases tumor growth in vivo. Thus, alphavbeta3 serves diverse biological functions during the progression from the nontumorigenic radial growth phase to the tumorigenic and-invasive vertical growth phase primary melanoma.

Adenoviridae↗
PubMed1998

The C8/144B monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells.

Stem cells are vital for the homeostasis of self-renewing tissues such as the hair follicle. Epithelial stem cells have been implicated in tumorigenesis and wound healing, and their manipulation may have wide ranging applications including gene therapy and tissue transplantation. Rodent hair follicle stem cells have been localized to an area of the follicle called the bulge, however, the identification and characterization of human hair follicle stem cells has been hampered by a lack of cellular markers for this area. We have determined that the C8/144B monoclonal antibody, originally generated against a short intracytoplasmic peptide of CD8, preferentially immunostains hair follicle bulge keratinocytes without staining the remaining hair follicle. Using expression cloning, we identified cytokeratin 15 as the keratinocyte protein recognized by the C8/144B monoclonal antibody. By delineating the bulge using this antibody, we demonstrated that bulge cells possess a stem cell phenotype characterized by their slowly-cycling nature, preferential proliferation at the onset of new hair follicle growth, high level of beta1 integrin expression, and expression of cytokeratin 19.

Adult↗
PubMed1998

UVB induces atypical melanocytic lesions and melanoma in human skin.

A direct causal relationship between ultraviolet (UV) light in the B range and melanoma development has not been demonstrated in humans; this study aims to establish causality. A total of 158 RAG-1 mice, grafted with human newborn foreskin, were separated into four groups and observed for a median of 10 months: 1) no treatment, 2) a single treatment with 7,12-dimethyl(a)benzanthracene (DMBA), 3) UVB irradiation at 500 J/m2 alone, three times weekly, and 4) a combination of DMBA and UVB. Twenty-three percent of 40 normal human skin grafts treated with UVB only and 38% of 48 grafts treated with the combination of DMBA and UVB developed solar lentigines within 5 to 10 months of treatment. Melanocytic hyperplasia was found in 73% of all UVB-treated xenografts. Histological melanocytic changes resembling lentigo and lentigo maligna were seen in several skin grafts treated with both DMBA and UVB. In one graft of an animal treated with a combination of DMBA and UVB, a human malignant melanoma, nodular type, developed. This experimental system demonstrates that chronic UVB irradiation with or without an initiating carcinogen can induce human melanocytic lesions, including melanoma.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Clinically recognized dysplastic nevi. A central risk factor for cutaneous melanoma.

OBJECTIVE: To investigate the relationship of number and type of nevi to the development of melanoma. DESIGN: Case-control study. SETTING: Outpatient clinics in referral hospitals. PATIENTS: Cases were 716 consecutive patients with newly diagnosed melanoma identified at 2 melanoma centers between January 1, 1991, and December 31, 1992. Stratified random sampling of patients from outpatient clinics was used to identify 1014 participating controls of the same age, sex, race, and geographic distribution as the melanoma cases. All study subjects underwent an interview, a complete skin examination, photography of the most atypical nevi, and, if the patient was willing, a biopsy of the most atypical nevus. MAIN OUTCOME MEASURES: Number and type of nevi on the entire body were systematically reported. All diagnoses of clinically dysplastic nevi were confirmed by expert examiners. RESULTS: Risk for melanoma was strongly related to number of small nevi, large nondysplastic nevi, and clinically dysplastic nevi. In the absence of dysplastic nevi, increased numbers of small nevi were associated with an approximately 2-fold risk, and increased numbers of both small and large nondysplastic nevi were associated with a 4-fold risk. One clinically dysplastic nevus was associated with a 2-fold risk (95% confidence interval, 1.4-3.6), while 10 or more conferred a 12-fold increased risk (95% confidence interval, 4.4-31). Congenital nevi were not associated with increased risk of melanoma. CONCLUSIONS: Although nondysplastic nevi confer a small risk, clinically dysplastic nevi confer substantial risk for melanoma. On the basis of nevus number and type, clinicians can identify a population at high risk of this epidemic cancer for screening and intervention.

Adult↗
PubMed1997

Proto-oncogene c-kit expression in malignant melanoma: protein loss with tumor progression.

The c-kit gene encodes a transmembrane receptor that has tyrosine kinase activity. c-kit plays a role in hematopoiesis, gametogenesis, and melanogenesis. c-kit is found in melanocytes, and there is evidence that expression is lost in melanoma. We studied 85 melanocytic lesions for c-kit by immunohistochemical techniques using a monoclonal antibody. The lesions included banal nevi, junctional and compound nevi with melanocytic dysplasia, nontumorigenic radial growth phase melanoma, tumorigenic vertical growth phase melanoma, and metastatic melanoma. We found intense membrane staining in normal melanocytes and mast cells. Staining in compound nevi was strongest in junctional and superficial dermal components, whereas dermal nevi showed weak reactivity. Dysplastic nevi stained strongly, particularly in junctional cells. In melanoma, strong reactivity was most prominent in radial growth phase disease, but there was little or no staining in vertical growth phase and metastatic melanomas. In summary, c-kit protein is expressed in normal melanocytes, benign nevi, dysplastic nevi and nontumorigenic melanoma, but expression is lost in tumorigenic primary melanomas and metastases. The role of c-kit loss in advanced melanoma requires additional investigation.

Disease Progression↗
PubMed1997

Melanoma cell lines from different stages of progression and their biological and molecular analyses.

The biological and molecular characteristics of cell lines from metastatic melanomas have been extensively studied but less is known about cells from the biologically earliest stage of primary melanoma. The overall success rate of establishing permanent cell lines from such lesions is only 10% of that for biologically late primary or metastatic melanomas, although our laboratory now has eight cell lines available. The cells are immortal but show reduced or no proliferation in soft agar and immunodeficient mice when compared with primary melanomas from the biologically advanced vertical growth phase. Metastatic melanoma cell lines from patients with familial melanoma or xeroderma pigmentosum are biologically similar to those from patients with spontaneous melanomas. Irrespective of the malignant stages, deletions and mutations can occur in exons 1-3 of the p16INK4A gene. DNA fingerprinting was then employed to demonstrate the uniqueness of individual cell lines and to confirm the identity of cell lines derived from same patients. These cell lines are an excellent resource to investigate melanoma progression.

Animals↗
PubMed1996

A prognostic model for predicting 10-year survival in patients with primary melanoma. The Pigmented Lesion Group.

OBJECTIVE: To develop a prognostic model, based on clinical and pathologic data that are routinely available to the clinician, that would estimate the chance for survival of a patient with primary cutaneous melanoma after definitive surgical therapy. DESIGN: Cohort analytical study. SETTING: University medical center. PATIENTS: 488 patients with primary cutaneous melanoma who had no apparent metastatic disease. Patients were followed prospectively for at least 10 years. An independent validation sample of 142 patients was used to assess the stability of the model. MEASUREMENTS: Six clinical and pathologic variables that predict survival and are readily available to the clinician were used to develop a prediction model. The variables were tested for their association with death by using a univariate logistic regression model. Point estimates were generated for the probability of surviving melanoma at 10 years. Variables that were statistically significantly associated with survival were retained for testing in a logistic regression model. RESULTS: 488 patients were followed prospectively for a median of 13.5 years (minimum, 10.0 years; maximum, 20.5 years). The overall 10-year survival of the study group was 78%. Four variables were found to be independent predictors of survival. Presented as adjusted odds ratios, from strongest to weakest relative predictive strength, these variables were tumor thickness (odds ratio, 50.8), site of primary melanoma (odds ratio, 4.4), age of the patient (odds ratio, 3.0), and sex of the patient (odds ratio, 2.0). The four-variable model was significantly more accurate than tumor thickness alone, particularly for predicting death. Overall, use of the model reduced the error rate of the prediction of death by 50%. CONCLUSIONS: A prognostic model that uses four readily accessible variables more accurately predicts outcome in patients with primary melanoma than does tumor thickness alone. This four-variable model can identify patients at high risk for the recurrence of disease, an identification that becomes increasingly important as adjuvant therapies are developed for treatment of melanoma.

Adult↗
PubMed1996

Neoplastic progression and prognosis in melanoma.

Most melanomas evolve through an initial stage known as radial growth phase (RGP), encompassing in situ and microinvasive malignancies in which the probability of cure approaches 100%. At the present time, despite a shift toward earlier recognition of melanoma, by the time of diagnosis roughly 70% of melanomas have evolved to a point, known as vertical growth phase (VGP) or tumorigenic melanoma, at which cure is not certain, and prognosis depends upon certain attributes of the neoplasm and the host. Attempts have been made to assemble these attributes into prognostic models to permit estimation of the probability of cure for individuals and for groups of patients. Attributes that have been identified as independent prognostic variables include thickness of the primary neoplasm, the numbers of mitotic figures, and the presence of tumor-infiltrating lymphocytes (TIL). Other biologically important prognostic variables are on the horizon, and some will likely be based on molecules (markers) expressed on neoplastic cells that show functional significance in mechanisms of metastasis.

Disease Progression↗
PubMed1996

Pathophysiology of overheating in a piglet model: findings compared with sudden infant death syndrome.

OBJECTIVE: To examine the nature of hyperthermia-induced pathophysiological changes in an animal model including effects on lung compliance. METHODOLOGY: Piglets were randomly assigned to heated or non-heated groups. Heated animals were warmed to 4 degrees C above normal body temperature while sedated and breathing spontaneously. Cardiorespiratory variables were recorded serially and haematological assessments and blood cultures taken at 0 and 6 h. After 6 h the animals were killed and a limited postmortem was performed. Control animals had all procedures without heating. RESULTS: Heated piglets developed tachycardia, hypotension and a metabolic acidosis in addition to tachypnoea, hypocapnic alkalosis and a neutrophil leucocytosis. Rectal temperature after death fell at the same rate in both groups. Lung histology revealed an excess of lung haemorrhage and alveolar oedema in the heated group. No significant group differences in dynamic lung compliance were demonstrated. CONCLUSIONS: The pathological changes that occur during hyperthermia are non-specific but not incompatible with those found in sudden infant death syndrome. There was no confirmation of the thesis that hyperthermia causes death by altering lung compliance.

Animals↗
PubMed1996

Recurrent wheezing in very preterm infants.

AIMS: To document the prevalence of, and identify risk factors for, recurrent wheezing treated with bronchodilators in the first year of life. METHODS: Parental history and neonatal data were collected prospectively in a regional cohort of very preterm infants (< 33 weeks). Data on maternal smoking, siblings at home, breast feeding, respiratory symptoms, and hospital re-admissions were documented at 12 months. RESULTS: Outcome data were available for 525/560 (95%) of survivors. The incidence of recurrent wheeze was 76/525 (14.5%) in very preterm infants and 20/657 (3%) in a cohort of term newborns. Significant risk factors for recurrent wheeze in very preterm infants were parental history of asthma, maternal smoking, siblings at home, neonatal oxygen supplementation at 28 days, 36, and 40 weeks of gestation. CONCLUSIONS: Wheezing respiratory illnesses are common in very preterm infants. The factors involved are similar to those in more mature infants, with the addition of immaturity and neonatal lung injury.

Bronchial Hyperreactivity↗
PubMed1996

Melanoma-associated expression of transforming growth factor-beta isoforms.

Melanocytic neoplasia is characterized by the aberrant overproduction of multiple cytokines in vitro. However, it is largely unknown how cytokine expression relates to melanoma progression in vivo. Transforming growth factor beta (TGF-beta) is a multifunctional cytokine commonly produced by cultured melanoma cells. The in situ expression of all three TGF-beta isoforms (TGF-beta1, -2, and -3) was determined immunohistochemically in melanocytes and in 51 melanocytic lesions using isoform-specific antibodies. Significant linear trends of expression were observed from melanocytes through nevi and primary and metastatic melanomas for all three isoforms. TGF-beta1 was expressed by some melanocytes and almost uniformly by nevi and melanomas. TGF-beta2 and -3 were not expressed in normal melanocytes but were expressed in nevi and early and advanced primary (radial and vertical growth phase) and metastatic melanomas in a tumor-progression-related manner. TGF-beta2 was heterogeneously expressed in advanced primary and metastatic melanomas, whereas TGF-beta3 was uniformly and highly expressed in these lesions. Thus, expression of TGF-beta isoforms in melanocytes and melanocytic lesions is heterogeneous and related to tumor progression, and expression of TGF-beta2 and TGF-beta3 commences at critical junctures during progression of nevi to primary melanomas.

Biomarkers, Tumor↗
PubMed1996

Granular cell myoblastoma of the cervical esophagus: MR findings.

Granular cell myoblastomas are uncommon, typically benign tumors. Involvement of the esophagus is rare, and frequently they are asymptomatic. We report a granular cell myoblastoma involving the cervical esophagus in a patient who had paralysis of the true vocal cord and progressive dysphagia. At MR imaging, the circumscribed mass was hypointense on T1-weighted images and mildly hyperintense on T2-weighted images, with homogeneous contrast enhancement.

Adult↗
PubMed1995

Desmoplasia and neurotropism. Prognostic variables in patients with stage I melanoma.

BACKGROUND: Desmoplastic melanomas with and without neurotropism are thought to be more clinically aggressive than other melanomas of comparable thickness. This study evaluates the prognostic significance of desmoplasia and neurotropism in Patients with Stage I cutaneous melanoma completely excised at the initial presentation of disease and prospectively studied for a minimum of 8 years. METHODS: Desmoplasia and neurotropism were evaluated as single prognostic predictors in survival outcome of cutaneous Stage I melanomas and as variables in the University of Pennsylvania Pigmented Lesion Study Group 8-year survival model for Stage I melanoma. In addition, the clinical presentation and follow-up of melanomas with desmoplasia and/or neurotropism was compared with that of other types of cutaneous Stage I melanoma in patients also followed for a minimum of 8 years. RESULTS: Neurotropism was associated with a statistically significant decrease in survival in patients with melanomas with desmoplasia. A decrease in survival also was observed in other types of melanoma with neurotropism, but the difference was not statistically significant. Melanomas with neurotropism had a statistically significant increase in local recurrence. Desmoplasia was not associated with a statistically significant decrease in survival. CONCLUSION: Desmoplasia is not associated with a statistically significant decrease in the prognosis of patients with primary cutaneous Stage I melanoma. The more clinically aggressive behavior of desmoplastic melanomas observed in previous studies may be secondary to initial misdiagnosis and/or inadequate margin assessment of these lesions. Neurotropism, however, is associated with a statistically significant decrease in survival in patients with desmoplastic melanomas and is most likely associated with decreased reduces patient survival in other melanoma types. Neurotropism is also related to an increase in the frequency of local recurrence of melanoma.

Female↗
PubMed1995

Skin cancer. Melanoma and other specific nonmelanoma skin cancers.

BACKGROUND: Malignant melanoma accounts for most of the growing mortality from skin cancer. However, survival rates are increasing for individual cases, probably because of earlier diagnoses. METHODS: Skin cancers collected by the SEER population-based data base between 1973 and 1987 are described in terms of their histologic classification and their distribution by sex, race, anatomical location, geographic locality, and time period of occurrence. RESULTS: There were 30,519 invasive skin cancers in the 15-year reporting period. Because the common basal cell and squamous cell cancers are not reportable to SEER, most of the cancers (28,206) were melanomas. In addition, 4386 in situ melanomas were reported. The rate of melanoma was 13-fold higher in whites than in blacks and 29% higher in white males than in white females. There was a 52% increase in the age-adjusted incidence rate for invasive melanoma and a 600% increase in the incidence rate of in situ melanoma over the 15-year period for whites and a 12% decrease in the incidence rate of invasive melanoma in blacks. The incidence of melanoma in the ear and trunk predominated in males, whereas melanoma of the lower limb predominated in females. Incidence rates and rate of increase of incidence of melanoma varied by anatomical subsite, sex, and geographic location within the United States. CONCLUSIONS: The variations among incidence rates of melanoma by sex, subsite, race, geographic location, and time period support prevailing theories of a solar cause for most but not all cases of this disease. Although melanoma rates are rising overall, the disproportionate rise in the rate of diagnosis of in situ compared with invasive melanoma suggests that melanomas are being diagnosed earlier.

Adolescent↗
PubMed1995

Neonatal herpes simplex infection: keys to early diagnosis.

OBJECTIVE: To highlight the clinical features of neonatal herpes simplex (HSV) infection that might facilitate earlier diagnosis. METHODOLOGY: Fifteen year retrospective review of proven neonatal HSV cases from a regional neonatal referral unit. RESULTS: Fifteen cases reviewed: 10 with central nervous system (CNS) disease, three with skin, eyes or mouth (SEM) disease and two with disseminated disease (DIS). A median 4 day delay occurred between symptom onset and hospital admission. All cases presented after maternity hospital discharge, most commonly with feeding problems and lethargy. Six patients presented with skin lesions; parental genital herpes was reported in three (20%) cases. Seven infants died, four without acyclovir treatment and three of 11 treated cases. Three of five CNS disease survivors and all infants with SEM disease were normal at follow up. CONCLUSIONS: Acyclovir improves outcome in neonatal HSV infection. To improve outcome further earlier recognition of the non-specific presenting features of the disease is required.

Acyclovir↗