Atypical cellular blue nevi (cellular blue nevi with atypical features): lack of consensus for diagnosis and distinction from cellular blue nevi and malignant melanoma ("malignant blue nevus").

The distinction of cellular blue nevi (CBN) with atypical features ["atypical" CBN (ACBN)] from conventional CBN and malignant melanomas related to or derived from CBN remains a difficult problem. Here, we report on the diagnosis of various cellular blue melanocytic neoplasms by 14 dermatopathologists who routinely examine melanocytic lesions. Three parameters were assessed: (1) for between rater analyses, we calculated interobserver agreement by the kappa statistic (regardless of whether the diagnosis was correct).

Claudin-1 overexpression in melanoma is regulated by PKC and contributes to melanoma cell motility.

Serial analysis of gene expression followed by pathway analysis implicated the tight junction protein claudin-1 (CLDN1) in melanoma progression. Tight junction proteins regulate the paracellular transport of molecules, but staining of a tissue microarray revealed that claudin-1 was overexpressed in melanoma, and aberrantly expressed in the cytoplasm of malignant cells, suggesting a role other than transport. Indeed, melanoma cells in culture demonstrate no tight junction function.

Morphological characterization of the breast in Proteus syndrome complicated by ductal carcinoma in situ.

Proteus syndrome (PS) is a severe, variable, and rare disorder with asymmetric and disproportionate overgrowth of body parts, cerebriform connective tissue nevi, epidermal nevi, dysregulated adipose tissue, and vascular malformations. It is associated with benign and occasionally malignant tumors. We report the first case of ductal carcinoma in situ (DCIS) in a 28-yr-old woman with PS who underwent a mastectomy for asymmetric overgrowth.

Dysplastic naevi with moderate to severe histological dysplasia: a risk factor for melanoma.

Background: The risk of malignant melanoma associated with histologically dysplastic naevi (HDN) has not been defined. While clinically atypical naevi appear to confer an independent risk of melanoma, no study has evaluated the extent to which HDN are predictive of melanoma.

Objectives: To estimate the risk of melanoma associated with HDN.

The effects of gp100 and tyrosinase peptide vaccinations on nevi in melanoma patients.

Background: A new approach to prevent disease recurrence in high-risk melanoma patients involves immunization with gp100 and tyrosinase peptides. This is the first study to examine the effects of such treatments on nevi.

Design: We studied biopsies of 'clinically atypical' nevi from 10 patients before and after peptide vaccination.

Gene expression profiling of human sarcomas: insights into sarcoma biology.

Sarcomas are a biologically complex group of tumors of mesenchymal origin. By using gene expression microarray analysis, we aimed to find clues into the cellular differentiation and oncogenic pathways active in these tumors as well as potential biomarkers and therapeutic targets. We examined 181 tumors representing 16 classes of human bone and soft tissue sarcomas on a 12,601-feature cDNA microarray.

Molecular alterations in primary prostate cancer after androgen ablation therapy.

Purpose: After an initial response to androgen ablation, most prostate tumors recur, ultimately progressing to highly aggressive androgen-independent cancer. The molecular mechanisms underlying progression are not well known in part due to the rarity of androgen-independent samples from primary and metastatic sites.

Experimental Design: We compared the gene expression profiles of 10 androgen-independent primary prostate tumor biopsies with 10 primary, untreated androgen-dependent tumors.

Invasion of human tissue ex vivo by Borrelia burgdorferi.

Borrelia burgdorferi sensu stricto is an etiological agent of Lyme disease. The lack of an adequate ex vivo system for human tissue infection is an obstacle to fully understanding the molecular mechanisms of invasion of tissue by B. burgdorferi and its adaptation within the human host.

Gleason score and pretreatment prostate-specific antigen in survival among patients with stage D2 prostate cancer.

Although multiple studies have addressed the prognostic importance of tumor differentiation in patients with clinically localized prostate cancer, few data are available in patients with metastatic disease. We evaluated and compared survival data in two groups of men with Whitmore stage D2 metastatic prostate cancer initially treated with hormonal therapy. A series of 76 patients with D2 metastatic disease were evaluated and treated at the National Cancer Institute (NCI) in conjunction with an additional cohort of 141 patients from the Louisiana State University School of Medicine (LSU).

Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor suppressor localized to a 9-Mb interval.

Loss of the short arm of chromosome 1 is frequently observed in many tumor types, including melanoma. We recently localized a third melanoma susceptibility locus to chromosome band 1p22. Critical recombinants in linked families localized the gene to a 15-Mb region between D1S430 and D1S2664.

Immunohistochemistry of normal human knee synovium: a quantitative study.

Objective: To describe the immunohistochemical characteristics of knee synovium from normal healthy subjects.

Methods: 12 healthy subjects underwent needle biopsy of knee synovium. Using antibodies directed against CD3, CD4, CD8, L26, Kp-1,and HLA-DR, detailed quantitative immunohistochemical analysis of various cell subpopulations was undertaken.

Generation and analysis of melanoma SAGE libraries: SAGE advice on the melanoma transcriptome.

In this study, we generated three SAGE libraries from melanoma tissues. Using bioinformatics tools usually applied to microarray data, we identified several genes, including novel transcripts, which are preferentially expressed in melanoma. SAGE results converged with previous microarray analysis on the importance of intracellular calcium and G-protein signaling, and the Wnt/Frizzled family.

Metastatic nevoid melanoma in a 4 1/2-year-old child.

Background: Childhood melanoma is a rare and controversial diagnosis.

Methods: We present the case of a 4 1/2-year-old child found to have an expanding, elevated pigmented lesion on her back.

Results: The biopsy showed a symmetrical, well circumscribed lesion.

Lyme-associated parkinsonism: a neuropathologic case study and review of the literature.

Neurological complications of Lyme disease include meningitis, encephalitis, dementia, and, rarely, parkinsonism. We present a case of striatonigral degeneration, a form of multiple system atrophy, in Lyme-associated parkinsonism. A 63-year-old man presented with erythema migrans rash, joint pains, and tremors.

Are en face frozen sections accurate for diagnosing margin status in melanocytic lesions?

To assess the diagnostic accuracy of margin evaluation of melanocytic lesions using en face frozen sections compared with standard paraffin-embedded sections, we studied 2 sets of lesions in which en face frozen sections were used for analysis of surgical margins (13 from malignant melanomas [MMs] and 10 from nonmelanocytic lesions [NMLs]). Routine permanent sections were cut after routine processing. The slides were mixed and coded randomly.

A phase I/II study of high-dose tamoxifen in combination with vinblastine in patients with androgen-independent prostate cancer.

In this phase I/II clinical trial the antitumor activity of high-dose tamoxifen when administered in combination with vinblastine was assessed and the toxicity profile of this combination characterized. All 25 patients enrolled in this study were required to have androgen-independent prostate cancer and to maintain androgen ablation during treatment. Vinblastine was given by continuous infusion over 5 days.

Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell activation. Blockade of CTLA-4 has been shown in animal models to improve the effectiveness of cancer immunotherapy. We thus treated 14 patients with metastatic melanoma by using serial i.

Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder characterized by smooth-muscle tumors of the skin and uterus and/or renal cancer. Although the identification of germline mutations in the fumarate hydratase (FH) gene in European families supports it as the susceptibility gene for HLRCC, its role in families in North America has not been studied. We screened for germline mutations in FH in 35 families with cutaneous leiomyomas.

Molecular differentiation of high- and moderate-grade human prostate cancer by cDNA microarray analysis.

The prognosis of men with moderate-grade prostate cancer is uncertain. At present, there are few if any reliable molecular markers that can distinguish moderate-grade tumors from those that behave more aggressively. To better understand the molecular basis of human prostate cancer and potentially provide information toward more accurate prognosis, we measured and analyzed gene expression profiles of 13 high- and moderate-grade human prostate tumors using cDNA microarrays.

Evaluation of ethanol-fixed, paraffin-embedded tissues for proteomic applications.

We previously reported that ethanol fixation and paraffin embedding of tissues produce excellent histomorphology and good preservation of macromolecules. Here, we present a detailed evaluation of ethanol-fixed tissues for proteomic initiatives. When proteins were extracted from ethanol-fixed, paraffin-embedded prostate tissue, resolved by two-dimensional gel electrophoresis (2-DE), and stained by standard methods, several hundred protein molecules could be detected and successfully analyzed by mass spectrometry.

Parathyroid hormone-related protein and hypercalcemia in patients with metastatic melanoma: case report and review.

Hypercalcemia associated with malignancy has been attributed to osteolytic processes secondary to bony metastases and to humoral factors causing increased bone resorption and decreased renal excretion of calcium. Parathyroid hormone-related protein (PTH-rP) is a humoral factor that has been associated with hypercalcemia in renal cell carcinoma, squamous cell carcinoma, and bladder carcinoma. Hypercalcemia does occur in patients with melanoma; however, few studies have reported on hypercalcemia in these patients, and even fewer have described a direct connection to PTH-rP.

PAGE4 is a cytoplasmic protein that is expressed in normal prostate and in prostate cancers.

PAGE4 is an X chromosome-linked cancer-testis antigen that was identified by expressed sequence tags database mining and a functional genomic approach. PAGE4 is preferentially expressed in normal male and female reproductive tissues and also in a variety of cancers including prostate. In the present study, we have used in situ hybridization to show that PAGE4 mRNA is expressed only in the epithelial cells of normal and prostate-cancer specimens.