Levels of cyclin D1 and D3 in malignant melanoma: deregulated cyclin D3 expression is associated with poor clinical outcome in superficial melanoma.

We examined 172 primary (110 superficial and 62 nodular) and 73 metastatic melanomas, as well as 10 benign nevi, for protein expression of cyclin D1 and cyclin D3 and evaluated the relationship between deregulated protein levels and clinical outcome. For both proteins, a heterogeneous nuclear staining pattern was observed. Cyclin D3 was expressed by 96% of primary and 97% of metastatic melanomas. The corresponding percentages for cyclin D1 were 62% and 29%, respectively. In benign nevi, only rare cyclin D3-positive cells and no cyclin D1-positive cells were observed. High levels of cyclin D3 (>5% of the cells stained) were detected in 26 of 62 (42%) nodular melanomas and in 22 of 110 (20%) superficial tumors, whereas no such difference was observed with respect to cyclin D1. In superficial melanomas, a significant concordant staining pattern was observed between cyclin D1 and cyclin D3 (P = 0.0009), cyclin D1 and Ki-67 (P = 0.0001), cyclin D1 and cyclin A (P = 0.02), cyclin D3 and Ki-67 (P < 0.00001), and cyclin D3 and cyclin A (P = 0.002). Kaplan-Meier analysis revealed that high levels of cyclin D3 were an indicator of early relapse and decreased overall survival for patients with superficial (P = 0.001 and P = 0.009, respectively) but not nodular (P = 0.64 and P = 0.23) melanoma. Cyclin D1 did not have any impact on disease-free and overall survival for either of the subtypes. In conclusion, our results suggest that deregulation of cyclin D3 expression leading to increased proliferation may be a prognostic factor for superficial melanoma, whereas deregulated cell cycle machinery seems to have little impact on disease progression of nodular melanoma.

[Diagnostic delay in malignant melanoma]. / Diagnostisk forsinkelse ved malignt melanom.

BACKGROUND: Malignant melanoma accounts for 1 to 3% of all cancers and has been the most rapidly increasing type of cancer during the last decades. Early diagnosis and treatment favours a good prognosis. We wanted to investigate delays in the diagnostic process and patients' knowledge concerning malignant melanoma. MATERIAL AND METHODS: 457 patients with primary cutaneous malignant melanoma received a questionnaire through their physician; 352 (77%) returned the questionnaire. RESULTS: Median patient delay, defined as time between the patient's first observation of changes in a naevus and the first medical consultation, was eight weeks. Younger men had the longest patient delays. Median professional delay, defined as time from the first medical consultation to the time of diagnosis, was one week. 60% of the patients observing changes in a naevus did not initially seek medical advice, as they did not believe the changes were significant. In 65% of the cases, the patients themselves initiated the consultation. Television and other media were principal sources of information. INTERPRETATION: Public campaigns should be designed to reach younger men in particular and focus on self-examination of naevi and immediate contact with a physician when a suspicious lesion is discovered.