PubMed Health⌕ Search

Biomedical subjects

Richard A Scolyer

Publications and source records attributed to Richard A Scolyer.

At least 19 recordsLinked to original sources
PubMed2006

Progression in melanoma is associated with decreased expression of death receptors for tumor necrosis factor-related apoptosis-inducing ligand.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in melanoma by interaction with death receptors TRAIL-R1 (DR4) or TRAIL-R2 (DR5) on melanoma cells or resists apoptosis by interaction with decoy receptors TRAIL-R3 (DcR1) or TRAIL-R4 (DcR2). Studies on cell lines suggest that there is a wide variation in TRAIL death receptor expression; however, their expression on excised human melanoma is not well documented. In view of this, we studied death receptor expression on melanomas using monoclonal antibodies specific for these receptors. Immunohistochemical staining for DR4, DR5, and DcR1/DcR2 was performed on formalin-fixed paraffin-embedded sections of 100 cases of primary melanoma, metastatic melanoma, and benign nevi. Percentage expressions of DR4 versus DR5 in benign nevi, primary melanoma, and melanoma metastases were 40% versus 90%, 69% versus 98%, and 55% versus 66%, respectively. There were significant differences in the mean percentage of DR5-positive cells between different groups of melanocytic lesions. Percent expression was higher in thin (< or =1.0 mm) compared with thick primary melanoma (88.9% versus 66.9%), and expression was less in subcutaneous metastases (49%) and lymph node metastases (30.6%) (P < .005). Expression was also higher in compound nevi (57%) than dysplastic nevi (49%). DcR1/DcR2 was found in 75% of benign nevi, 62% of primary melanomas, and 74% melanoma metastases. The results showed a wide variation in the expression of death receptors for TRAIL between and within primary and metastatic melanoma and a decreased expression on the thick primary melanoma and metastatic melanoma. This suggests that melanoma may not respond to treatment with TRAIL unless given with agents that increase the expression of TRAIL death receptors.

Adolescent↗
PubMed2006

Low meprin alpha expression differentiates primary ovarian mucinous carcinoma from gastrointestinal cancers that commonly metastasise to the ovaries.

BACKGROUND: Currently, no specific immunohistochemical markers are available to differentiate primary mucinous epithelial ovarian cancer (MOC) from adenocarcinomas originating at other sites that have metastasised to the ovary, which may have an impact on patient management and prognosis. AIM: To investigate the expression of two intestinal markers, galectin 4 and meprin alpha, in mucinous carcinomas of the ovary and gastrointestinal tract. METHODS: Using immunohistochemical analysis, the expression of galectin 4 and meprin alpha was investigated in 10 MOCs and in 38 mucinous adenocarcinomas of colon, pancreas, stomach and appendix, the most common sites of origin of ovarian metastases. RESULTS: Total cytoplasmic galectin 4 expression was relatively consistent between the different carcinomas. Membranous meprin alpha expression was significantly lower in MOCs compared with gastrointestinal carcinomas. Moreover, meprin alpha expression showed greater discrimination between the ovarian and gastrointestinal carcinomas than the cytokeratins CK7 and CK20, the current standard immunohistochemical markers used to determine the tissue origin of mucinous carcinomas involving the ovaries. CONCLUSIONS: Meprin alpha is a useful additional marker in differentiating primary from secondary mucinous adenocarcinomas of the ovary.

Adenocarcinoma↗
PubMed2006

Epithelioid and spindle cell haemangioma of bone.

A case of epithelioid and spindle cell haemangioma of bone occurring in the proximal femur is presented. The tumour had typical microscopic features with a striking lobular pattern comprising spindled and epithelioid areas with admixed inflammatory cells. The case represents only the eighth reported example of this rare tumour, which appears to fit in the spectrum of epithelioid haemangioma. This is the first case to involve the proximal portion of a long bone. A review of the classification and features of similar vascular tumours of bone is presented.

Biopsy↗
PubMed2006

Surgical management of primary cutaneous melanoma: excision margins and the role of sentinel lymph node examination.

Surgical strategies for managing patients who have primary cutaneous melanoma have changed dramatically over the past 30 years. More conservative excision margins have been shown to be adequate, and routine complete lymph node dissection (CLND)has been abandoned since the sentinel node (SN) biopsy technique was introduced. Knowledge of a patient's SN status not only provides a reliable guide to prognosis, but also allows CLND to be avoided in 80% to 85% of patients. Recent clinical trial results suggest that SN biopsy, with immediate CLND if an SN is positive,confers a survival advantage in those who have metastatic disease in regional nodes. Minimally invasive and noninvasive methods of SN assessment, such as magnetic resonance spectroscopy, are being evaluated.

Humans↗
PubMed2006

The role of cell cycle regulatory proteins in the pathogenesis of melanoma.

The transformation of melanocytes to melanoma cells is characterised by abnormal proliferation resulting from alterations in cell cycle regulatory mechanisms. This occurs through alterations in the two major cell cycle regulatory pathways, the retinoblastoma (Rb) and p53 tumour suppressor pathways. This review summarises the current knowledge of alterations in these two pathways at G1/S transition and specifically the role of the key cell cycle regulatory proteins pRb, p16INK4a (p16), cyclin D1, p27Kip1 (p27), p53 and p21Waf1/Cip1 (p21) in the pathogenesis of melanoma. It also considers their prognostic significance. Current data indicate that alterations of cyclin kinase inhibitor (cdki) levels are implicated in the pathogenesis of melanoma and may be useful prognostic markers. However, large validation studies linked to comprehensive clinical follow up data are necessary to clarify the prognostic significance of cell cycle regulatory proteins in individual patients.

Animals↗
PubMed2006

Pravastatin-induced lichenoid drug eruption.

SUMMARY A 64-year-old woman presented with diffuse and numerous pigmented macules on her face and upper back. Histopathological examination of a skin punch biopsy of the rash showed a lichenoid dermatitis. The most likely offending drug was pravastatin. Cessation of pravastatin resulted in gradual fading of the pigmentation. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors have previously been reported to cause lichenoid drug eruptions.

Biopsy, Needle↗
PubMed2006

Myxoid variant of adrenocortical carcinoma: report of a unique case.

Myxoid variant of adrenocortical carcinomas (ACC) are rare, there being only 11 cases in the literature to date. Reported herein are the findings of a case, which in contrast to all previously reported myxoid ACC, was devoid of typical non-myxoid areas. The patient was a 61-year-old man in whom a left adrenal mass was detected during investigation of Cushing's syndrome. The adrenal was replaced by malignant cells and expanses of myxoid material. The cells were positive for melan-A, synaptophysin, vimentin and alpha-inhibin. The ultrastructural features of the cells were typical of adrenal cortical differentiation. The differential diagnosis of myxoid ACC includes extraskeletal myxoid chondrosarcoma, chordoma, myxoid adenocarcinoma, myxoma, lipomatous tumors, nerve sheath tumors, smooth muscle tumors, gastrointestinal stromal tumor and other sarcomas. The presence of myxoid material in a retroperitoneal lesion raises a broad differential diagnosis in which myxoid adrenocortical neoplasms should be included. Clinicoradiological correlation may be helpful, but special stains, immunohistochemistry and ultrastructural examination may be necessary to establish the diagnosis.

Adenocarcinoma↗
PubMed2005

An unusual variant of intraneural ganglion of the common peroneal nerve.

A highly unusual variant of an intraneural ganglion of the common peroneal nerve in a 30-year-old male is presented. There was extrusion of the contents of the cyst into the substance of the nerve, dissecting between the fibres and expanding the nerve in such a way that it mimicked an intraneural tumour clinically, radiologically and histologically. A comprehensive review of the entity is undertaken.

Adult↗
PubMed2005

Melanoma metastases in regional lymph nodes are accurately detected by proton magnetic resonance spectroscopy of fine-needle aspirate biopsy samples.

BACKGROUND: Nonsurgical assessment of sentinel nodes (SNs) would offer advantages over surgical SN excision by reducing morbidity and costs. Proton magnetic resonance spectroscopy (MRS) of fine-needle aspirate biopsy (FNAB) specimens identifies melanoma lymph node metastases. This study was undertaken to determine the accuracy of the MRS method and thereby establish a basis for the future development of a nonsurgical technique for assessing SNs. METHODS: FNAB samples were obtained from 118 biopsy specimens from 77 patients during SN biopsy and regional lymphadenectomy. The specimens were histologically evaluated and correlated with MRS data. Histopathologic analysis established that 56 specimens contained metastatic melanoma and that 62 specimens were benign. A linear discriminant analysis-based classifier was developed for benign tissues and metastases. RESULTS: The presence of metastatic melanoma in lymph nodes was predicted with a sensitivity of 92.9%, a specificity of 90.3%, and an accuracy of 91.5% in a primary data set. In a second data set that used FNAB samples separate from the original tissue samples, melanoma metastases were predicted with a sensitivity of 87.5%, a specificity of 90.3%, and an accuracy of 89.1%, thus supporting the reproducibility of the method. CONCLUSIONS: Proton MRS of FNAB samples may provide a robust and accurate diagnosis of metastatic disease in the regional lymph nodes of melanoma patients. These data indicate the potential for SN staging of melanoma without surgical biopsy and histopathological evaluation.

Biopsy, Fine-Needle↗
PubMed2005

A sentinel node biopsy does not increase the incidence of in-transit metastasis in patients with primary cutaneous melanoma.

BACKGROUND: It has been suggested that performing a sentinel node biopsy (SNB) in patients with cutaneous melanoma increases the incidence of in-transit metastasis (ITM). METHODS: ITM rates for 2018 patients with primary melanomas > or =1.0 mm thick treated at a single institution between 1991 and 2000 according to 3 protocols were compared: wide local excision (WLE) only (n = 1035), WLE plus SNB (n = 754), and WLE plus elective lymph node dissection (n = 229). RESULTS: The incidence of ITM for the three protocols was 4.9%, 3.6%, and 5.7%, respectively (not significant), and as a first site of recurrent disease the incidence was 2.5%, 2.4%, and 4.4%, respectively (not significant). The subset of patients who were node positive after SNB and after elective lymph node dissection also had similar ITM rates (10.8% and 7.1%, respectively; P = .11). On multivariate analysis, primary tumor thickness and patient age predicted ITM as a first recurrence, but type of treatment did not. Patients who underwent WLE only and who had a subsequent therapeutic lymph node dissection (n = 149) had an ITM rate of 24.2%, compared with 10.8% in patients with a tumor-positive sentinel node treated with immediate dissection (n = 102; P = .03). CONCLUSIONS: Performing an SNB in patients with melanoma treated by WLE does not increase the incidence of ITM.

Adolescent↗
PubMed2005

Outcome in 846 cutaneous melanoma patients from a single center after a negative sentinel node biopsy.

BACKGROUND: A negative sentinel node biopsy (SNB) implies a good prognosis for melanoma patients. The purpose of this study was to determine the long-term outcome for melanoma patients with a negative SNB. METHODS: Survival and prognostic factors were analyzed for 836 SNB-negative patients. All patients with a node field recurrence were reviewed, and sentinel node (SN) tissue was reexamined. RESULTS: The median tumor thickness was 1.7 mm, and 23.8% were ulcerated. The median follow-up was 42.1 months. Melanoma specific survival at 5 years was 90%, compared with 56% for SN-positive patients (P < .001). On multivariate analysis, only thickness and ulceration retained significance for disease-free and disease-specific survival. Five-year survival for patients with nonulcerated lesions was 94% vs. 78% with ulceration. Eighty-three patients (9.9%) had a recurrence. Twenty-seven patients developed recurrence in the regional node field, and in 22 of these, it was the first recurrence site. Six developed local recurrence, 17 an in-transit metastasis, and 58 distant disease. The false-negative rate was 13.2%. SN slides and tissue blocks were further examined in 18 patients with recurrence in the node field, and metastatic disease was found in 3 of them. CONCLUSIONS: This large, single-center study confirms that patients with a negative SNB have a significantly better prognosis than those with positive SNs. In those with a negative SNB, primary tumor thickness and ulceration are independent predictors of survival. Incorrect pathologic diagnosis contributed to only a minority of the false-negative results in this study.

False Negative Reactions↗
PubMed2005

Transforming growth factor-beta1 immobilises dendritic cells within skin tumours and facilitates tumour escape from the immune system.

Human skin tumours often regress spontaneously due to immune rejection. Murine skin tumours model this behaviour; some regress and others progress in syngeneic immunocompetent hosts. Previous studies have shown that progressor but not regressor skin tumours inhibit dendritic cell (DC) migration from the tumour to draining lymph nodes, and transforming growth factor-beta1 (TGF-beta1) has been identified as a responsible factor. To determine whether increased production of TGF-beta1 in the absence of other differences inhibits DC migration from the tumour and enables it to evade immune destruction, a murine regressor squamous cell carcinoma clone was transfected with the gene for TGF-beta1. This enhanced growth in vitro and in vivo, causing it to become a progressor. TGF-beta1 transfection reduced the number of infiltrating DCs by about 25%. Quantitation of CD11c+ E-cadherin+ (epidermally derived) DCs in lymph nodes determined that TGF-beta1 reduced the number of DCs that migrated from the tumour to undetectable levels. This was supported by showing that TGF-beta1 reduced DC migration from cultured tumour explants by greater than tenfold. TGF-beta1 transfection also reduced the number of infiltrating CD4 and CD8 T cells. Thus, TGF-beta1 production by skin tumours is sufficient to immobilise DCs within the tumour, preventing their migration to lymph nodes. This reduces the number of T cells that infiltrate the tumour, preventing regression. Thus, TGF-beta1 is a key regulator of whether skin tumours regress or progress.

Animals↗
PubMed2005

Selective sentinel lymphadenectomy: progress to date and prospects for the future.

The sentinel node (SN) concept was clearly outlined by Virchow in the mid-nineteenth century, and Braithwaite used the term "glands sentinel" in 1923. However, it was not until Morton, Cochran et al. published their landmark report in 1992 that the clinical relevance of the SN was fully appreciated. Since then, the validity of the concept has been confirmed in studies undertaken at a number of centers worldwide. It has become clear that SN status accurately reflects the status of the entire regional node field, not only in patients with melanoma but also in those with breast cancer and a wide range of other primary malignancies. New insights into lymphatic anatomy have been gained by preoperative lymphoscintigraphy, and the original blue dye mapping technique for SN identification has been supplemented by intraoperative use of a hand-held gamma probe to identify radioactivity in colloid particles injected at the primary tumor site. It has become clear that all three methods are required to achieve optimal accuracy of SN identification. Although SN assessment provides very important prognostic information, the results of randomized trials must be awaited to determine whether selective sentinel lymphadenectomy, with full regional node dissection if a positive SN is found, is of any therapeutic value. It is possible that SN positivity is merely a marker of disease that has the potential for hematogenous dissemination and systemic metastasis. As follow-up times extend, reported false-negative SN rates are increasing, and ways to reduce these false-negative rates are therefore being actively sought. Attempts are being made to increase the accuracy of SN identification, and to confirm true SN identity both at the time of surgery and retrospectively. The ultimate objective is to develop minimally invasive and even non-invasive methods of SN assessment, Proton magnetic resonance spectroscopy is one technique that might make it possible to achieve this goal, and avoid the present morbidity and cost of operative SN removal.

Forecasting↗
PubMed2005

In vivo and ex vivo proton MR spectroscopy of primary and secondary melanoma.

In vivo magnetic resonance (MR) spectroscopy at 1.5T was performed on a large polypoid cutaneous melanoma, and two enlarged lymph nodes containing metastatic melanoma, from three patients. Spectra were acquired in vivo from voxels wholly within the primary tumour or secondary lymph node and were thus uncontaminated by signals from adjacent tissue. Tissue biopsies taken after resection of primary tumours and secondary lymph nodes were examined by 8.5T magnetic resonance spectroscopy (MRS) and the results compared with the in vivo spectra, and with spectra from normal skin and a benign skin lesion. There was good agreement between the dominant features of 1.5T spectra acquired in vivo and 8.5T spectra acquired from resected tissue. However, less intense resonances observed at 8.5T in malignant biopsy tissue were not consistently observed at 1.5T in vivo. In vivo spectra from primary and metastatic melanoma showed high levels of choline metabolites. An intense lactate resonance was also present in the in vivo spectrum of primary melanoma. All 8.5T spectra of biopsies from primary and secondary melanoma showed high levels of choline metabolites and lactate, and additional resonances consistent with elevated levels of taurine, alanine, lysine, and glutamate/glutamine relative to normal and benign tissue. Elevated levels of choline, lactate, taurine, and amino acids appear to be clinically useful markers for identifying the pathology of primary and metastatic melanoma.

Adult↗