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Background and aims--The Tage4 gene (tumour associated glycoprotein E4) is overexpressed in rat colon tumours and Min mouse intestinal adenomas. The rat Tage4 protein has approximately 40% identity with human [...]

Objectives: To describe circumstances of the diagnosis and access to dermatological care for patients with cutaneous melanoma (CM) and to investigate factors associated with early detection., Design: Retrospective population-based study of incident cases of invasive CM in 2004, using questionnaires to physicians and a survey of cancer registries and pathology laboratories., Setting: Five regions in northeastern France., Patients: Six hundred fifty-two patients who were referred to dermatologists by general practitioners (group 1) or by other specialists (group 2), who directly consulted a dermatologist for CM (group 3), or who were diagnosed as having CM during a prospective follow-up of nevi (group 4) or when consulting a dermatologist for other diseases (group 5)., Main Outcome Measures: Characteristics of patients, tumors, and patients' residence in each group, including the geographical concentration of dermatologists. We performed multivariate analysis of these factors to determine association with Breslow thickness., Results: Age, tumor location, Breslow thickness, ulceration, histological type, and geographical concentration of dermatologists significantly differed among groups. Patients consulting dermatologists directly formed the largest group (45.1%). Those referred by general practitioners (26.1%) were the oldest and had the highest frequency of thick (>3 mm), nodular, and/or ulcerated CM. Patients from groups 4 (8.4%) and 5 (14.1%) had the thinnest CMs. Ulcerated and/or thick tumors were absent in group 4. In multivariate analysis, histological types superficial spreading melanoma and lentigo maligna melanoma, younger age, high concentration of dermatologists, and detection by dermatologists were significantly associated with thinner CMs., Conclusion: Easy access of patients to dermatologists, information campaigns targeting elderly people, and education of general practitioners are complementary approaches to improving early detection.

Objective: To describe current management of cutaneous melanoma (CM) and identify factors accounting for disparities., Design: Retrospective population-based study using survey of cancer registries and pathology laboratories, and questionnaires to physicians., Setting: Five regions covering 19.2% of the French territory and including 8.2 million inhabitants., Patients: Incident cases of patients with stage I to stage II (hereinafter, stage I-II) tumors staged according to the American Joint Committee on Cancer Staging guidelines and nodal stage III CM in 2004., Main Outcome Measures: Modalities of diagnosis and excision, surgical margins, sentinel lymph node biopsy, adjuvant therapies and surveillance procedures, and their variations according to age, sex, residence, location of primary CM, Breslow thickness, type of physicians, modalities of decisions, and health care patterns., Results: Clinical stage I-II CMs (n = 710 cases) slightly predominated in females (53%), with a lower mean Breslow thickness (1.4 mm) than in males (1.9 mm). Initial excisions were most often performed by private dermatologists and wide excisions by surgeons. Narrow margins (8%) were associated with advanced age, higher Breslow thickness, and head location. Sentinel lymph node biopsy was performed in 34% of CMs thicker than 1.0 mm, depending on geographical regions, distance from reference centers, and health care patterns. Adjuvant therapies (mainly low-dose interferon) were proposed in 53% of thick CMs (>1.5 mm), depending on the patient's age and geographical region. In contrast with French recommendations, surveillance procedures frequently included systematic medical imaging. Stage III nodal CMs (n = 89 cases) predominated in males (62%). After lymphadenectomy, adjuvant therapies (including high-dose interferon in 32% of cases and chemotherapies in 24% of cases) were proposed in 68% of cases, depending on the patient's age and geographical region. A complete 1-year high-dose interferon regimen was administered in less than 10% of cases., Conclusion: Large disparities still exist in the management of CM in France, depending to a greater extent on medical and geographical environment than on the characteristics of either patients or tumors.

The CD155 gene is a member of the immunoglobulin superfamily. We first demonstrate the existence of soluble CD155 (sCD155) isoforms in culture medium conditioned by CD155-expressing cells, in human serum and in cerebrospinal fluid. sCD155 concentration was measured in human serum and cerebrospinal fluid using a specific ELISA. Analysis of conditioned media indicated that sCD155 release does not require protease activity. In order to determine which tissues are responsible for sCD155 expression, we have quantified CD155 mRNAs in human normal tissues. The highest expression was observed in liver. The CD155alpha transcript is the most abundant and the proportion of the CD155beta and CD155gamma variants was similar between the tissues. Finally, serum purified sCD155 reduces poliovirus entry mediated by membrane-bound CD155. The high level of CD155 synthesis in many tissues and the presence of sCD155 in biological fluids suggest the existence of an important role for the protein in cellular function.

The Tage4 gene (Tumor-Associated Glycoprotein E4) is a member of the immunoglobulin superfamily overexpressed in rat colon tumors and Min mouse intestinal adenomas. The Tage4 cDNA presents approximately 60% identity with the human CD155, a member of the immunoglobulin superfamily coding for a transmembrane protein capable of serving as an entry receptor for poliovirus, porcine pseudorabies virus and bovine herpesvirus 1. We determined the structure of the Tage4 gene. This gene covers approximately 15 kb and is composed of eight exons and seven introns. We also isolated approximately 2 kb of the 5' flanking region of the Tage4 gene and demonstrated the existence of closely clustered transcription start sites. No splicing variant was identified by RT-PCR indicating that the Tage4 gene is transcribed as a unique mRNA. Finally, the protein encoded by the Tage4 gene was tested for ability to mediate entry of several viruses. These structural and functional features of the rat Tage4 gene were compared to those of the human CD155 gene. The results indicated that the Tage4 gene is probably orthologous to the gene for CD155.