To investigate whether the course of primary melanoma disease correlates with expression of the various components of the proteolytic plasminogen activation (PA) system, immunohistochemical stainings for activators of plasminogen (tissue type (tPA) and urokinase type (uPA)), inhibitors of plasminogen activation (type 1 (PAI-1) and type 2 (PAI-2)) and the receptor for uPA (uPAR) were performed on 214 routinely processed melanoma lesions. All lesions were primary cutaneous melanomas, minimally 1.5 mm thick, and derived from patients with only local disease at the moment of diagnosis (clinically stage II (T 3–4 N 0 M 0), American Joint Committee on Cancer). Median patient follow-up was 6.1 years. Single variables as immunohistochemical staining results (extent of tumour cell staining, pattern of tumour cell staining and for some components also staining of stromal cells), histopathological and clinical parameters as well as treatment variables were analysed in order to assess their prognostic importance, in terms of time to recurrence, time to distant metastasis and duration of survival. The extent of tPA tumour cell positivity, categorized as 0–5%, 6–50% and 51–100%, appeared to be of importance for these end-points. Lesions with 51–100% tPA-positive tumour cells were found to have the best prognosis, whereas lesions with 6–50% tPA-positive tumour cells had the worst. Moreover, the prognostic significance of Breslow thickness, microscopic ulceration and sex was confirmed in this study. Multivariate analyses, incorporating these relevant factors, showed that the extent of tPA tumour cell positivity was an independent prognostic factor for distant metastasis-free interval (P= 0.012) and for the duration of survival (P= 0.043). © 2000 CancerResearch Campaign

K-ras and p53 gene mutations are known to occur in high frequencies in sporadic colorectal cancers, but findings are inconsistent in hereditary nonpolyposis colorectal cancer (HNPCC). We compared K-ras codon 12 and 13 gene mutations and p53 protein overexpression in 48 HNPCC (positive for Amsterdam criteria) and 59 sporadic colorectal adenomas, to examine whether they may represent similar or different molecular pathways to cancer. In sporadic adenomas K-ras mutations were detected in 32% and p53 overexpression in 31% of the cases. Similarly, K-ras mutations and p53 overexpression were both found in 25% of HNPCC adenomas. The frequencies of these abnormalities were not significantly different between HNPCC and sporadic adenomas. When taking differences in adenoma size into account, the frequencies were even more similar. In conclusion, these results suggest a similar molecular pathway to adenomas in HNPCC and sporadic carcinogenesis, with respect to involvement of K-ras and p53.

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