Prognostic Classification of Malignant Melanomas by Combining Clinical, Histological, and Immunohistochemical Parameters

Abstract

In a retrospective study the prognostic relevance of clinical, histopathological, immunohistochemical, and flow-cytometric parameters in primary malignant melanomas was evaluated using both the receiver operating characteristic ROC procedure and the logistic regression model. The proteolytic enzymes collagenase IV, cathepsin B, and cathepsin D proved to be significant prognostic factors. Combining the results obtained with these enzymes with gender, anatomic site, tumour thickness, Clark’s level, ulceration, pattern of invasive growth, and presence of large round cells resulted in greatly improved discrimination between metastasized and non-metastasized cases. It is anticipated that this method could allow for precise individual prognostic characterization and in particular for identification of high-risk patients for adjuvant therapy.

Function of Liver Activation-Regulated Chemokine/CC Chemokine Ligand 20 Is Differently Affected by Cathepsin B and Cathepsin D Processing

“…In this report, we identified new substrates among the chemokine family for Cath-D, and we characterized for the first time the processing in vitro of a large spectrum of chemokines by Cath-B. Both cathepsins are generally overexpressed in neoplastic tissues and have been previously extensively studied as possible prognostic factors in a variety of human cancers including breast cancer (46) and malignant melanoma (19,47). In general, receptor binding and chemokine functionality are modulated by epitopes in the N-terminal region of chemokines (1).…”

“…Analysis of these peptides by mass spectroscopy and N-terminal sequencing led to the identification of three N-terminal peptides, CCL20 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] , CCL20 , and CCL20 , an internal peptide, CCL20 , a C-terminal peptide of 12 aa, CCL20 59 -70 and full-length CCL20. CCL20 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] and CCL20 were held together by disulfides as demonstrated by MALDI analysis of this column fraction after reducing with DTT. Cleavage by Cath-B was very rapid and also complete and generated the distinct cleavage product CCL20 (Fig.…”

“…Thus, the interrelationship between chemokines and members of the cathepsin family, such as cathepsin D (Cath-D) and cathepsin B (Cath-B), may play an important role in tumor biology. Indeed, both cathepsins not only facilitate tumor progression (17) but may have a prognostic value in patients with breast cancer (17,18) and malignant melanoma (19). We therefore reasoned that the generation of an antitumoral immune response or cancer cell motility may be modulated by Cath-D and Cath-B generated by the tumor or reactive stroma.…”

Prognosticators of melanoma, the melanoma report, and the sentinel lymph node

“…Some studies have shown a significant tendency for the epithelioid vertical growth phase melanoma to manifest metastases preferentially over other vertical growth phase morphologies. 23 …”

Bedeutung von Matrix-degradierenden Enzymen für die Melanomprogression

“…Andere Autoren fanden zwar auch eine steigende Expression von Cathepsin B, H, L und D in Tumorzellen beim Vergleich von Melanoma in situ, primären Melanomen und Melanommetastasen, konnten aber keine signifikante Korrelation zwischen dem Anteil an positiven Tumorzellen und dem weiteren Krankheitsverlauf feststellen[35]. Um die klinische und prognostische Relevanz der Expression dieser Proteinasen für die Melanomerkrankung besser beurteilen zu können, wurde in einer retrospektiven Studie die Expression von Kollagenase IV, Cathepsin B und Cathepsin D mit bekannten klinischen und histologischen Kriterien kombiniert[50]. Die Ergebnisse zeigten, dass eine Unterscheidung von metastasierenden und nicht metastasierenden Melanomen erleichtert wird, wenn etablierte prognostische Kriterien mit der Expression von Kollagenase IV, Cathepsin B und Cathepsin D kombiniert werden.…”