As a variety of endogenous factors (e

As a variety of endogenous factors (e.g. Our results can be interpreted from different aspects: on the one hand, MT-negative melanoma thinner than 1.0?mm MBP146-78 practically never cause any further problems. There were only three cases of metastasis from an MT-negative melanoma thinner than 1.0?mm (three out of 1067 MT-negative cases, 0.28%); two of them had unique histological indicators of regression. In our cohort, none of the patients with MBP146-78 tumours 0.5?mm (591 patients with 54/9.1% MT positive) developed metastasis in the subsequent years. This may assure such patients of their good long-term outcome. So it should be deliberated if MT-negative patients with melanomas thinner than 1.0?mm could be controlled more generously without ultrasound- or X-ray-staging examinations. On the other hand, MT-positive melanoma thinner than 1.0?mm are at a greater risk of developing metastasis and succumbing to their neoplastic disease. In our study populace, 5.3% of the patients in this low-risk group (nine out of 170 MT-positive melanomas 1.0?mm) showed a progression of their disease; their relative risk is usually roughly comparable to MT-negative melanoma with a thickness of 2.1C4?mm. This may be used to more carefully follow up these patients and/or probably even serve as a tool to indicate and perform sentinel lymph node biopsy. Moreover, this group of patients could probably profit from adjuvant treatment. Metallothionein overexpression probably has an additional value. In stage IV melanoma patients, anticancer drugs, as well as irradiation therapy, are known to often show only a humbled rate of clinical responses. These therapeutic failures may partially be related to Rabbit Polyclonal to BAIAP2L2 an enhanced MT overexpression in tumour cells, although the involvement of MT in conferring resistance to chemotherapeutics still remains under conversation (Chin em et al /em , 1993; Hishikawa MBP146-78 em et al /em , 1997; Okazaki em et al /em , 1998; Cherian em et al /em , 2003). As a variety of endogenous factors (e.g. glucocorticosteroids, ILs, IFN em /em , TNF- em /em ) are involved in the induction of the synthesis of intracellular MT, one may suggest that this may lead to an overprotection of tumour cells against apoptosis, and, on the other hand, supporting the metastatic behaviour of the tumour (Karin em et al /em , 1985; Karasawa em et al /em , 1987; Nath em et al /em , 1988; Schroeder and Cousins, 1990; Sato and Sasaki, 1992; Tsangaris and Tzortzatou-Stathopoulou, 1998; Miles em et al /em , 2000; Nishimura em et al /em , 2000). In summary, our data confirm previous results of retrospective and much smaller studies in melanoma, outlining that MT overexpression is usually a useful and elegant tool for prognostication (Zelger em et al /em , 1993; Goldmann em et al /em , 1998; Sugita em et al /em , 2001). This marker is usually highly significant and impartial of tumour thickness and already predictive in low-risk melanomas thinner than 1.0?mm. These investigations by immunohistochemical labelling on archival paraffin material are easy to assess and perform in routine pathology and dermatopathology laboratories and the costs are limited. Acknowledgments We thank Dr P Puffer, private pathologist in Innsbruck, for allocating MBP146-78 a great number of tumour samples for the MT investigations. We are also greatly indebted to Dr V Mayr and L Richardsen for their help in the data collection and to B Moser and N Greier for their technical assistance..