Maspin expression and melanoma progression: a matter of sub-cellular localization

Abstract

Maspin, a member of the serpin family of protease inhibitors, is involved in key processes of cancer progression. Its biological activity seems to be cancer and compartment specific, with the protein acting either as a suppressor or as a tumor promoter in different cancer types. Characterization of maspin expression and its sub-cellular localization in melanoma is missing, hence, we aim to investigate its possible association with melanoma prognostic factors and disease progression. Nuclear and cytoplasmic maspin expression were evaluated on 60 nevi, 152 primary lesions, and 106 melanoma metastases using tissue microarrays and immunohistochemistry. The association between maspin immunoreactivity and patient's clinic-pathological features was evaluated. Multivariate logistic models and survival analyses were performed for maspin expression in primary melanomas. Nuclear maspin was detected in 8% nevi, 49% primary melanomas, and 28% metastases, whereas cytoplasmic maspin in 12% nevi, 18% primary lesions, and 9% metastases. In univariate analysis, nuclear maspin expression in primary melanomas was significantly associated with melanoma prognostic factors (nodular histotype, tumor thickness, mitotic rate, and ulceration) and disease stage, whereas cytoplasmic maspin was observed at higher frequency in thin superficial spreading melanomas, without mitosis. In multivariate analysis, nuclear maspin remained significantly associated with risk of developing a tumor prone to disease progression and, accordingly, with significantly shorter disease-free and overall survival. In this study, maspin was expressed at highest frequency in primary lesions and when expressed in the nuclei, was significantly associated with poor prognostic markers, melanoma recurrence, and worse survival. The present study suggests a tumor-suppressive effect of cytoplasmic maspin and a tumor-promoting effect of nuclear maspin, which open the discussion on its potential use in cancer therapy. Modern Pathology (2014) 27, 412-419; doi:10.1038/modpathol.2013.157; published online 13 September 2013Keywords: biomarker; maspin; melanoma; tissue microarrays Melanoma is a malignant neoplasm that originates from melanocytes and it is characterized by frequent local recurrence, early metastasis, and refractoriness to chemotherapy and biological treatment. 1 With early diagnosis and adequate surgical treatment of primary tumors (Stage I patients), the 5-year survival rate is 495%. 2 However, once melanoma has metastasized to distant sites, life expectancy dramatically declines, with 1-year survival rate of 33% for patients with Stage IV metastatic disease. 2 Primary tumor thickness, ulceration, and mitotic rate, together with the presence of lymph node and systemic metastases, are the histopathologic criteria used for melanoma staging to predict disease outcome in terms of life expectancy and survival rates. 2 However, a significant minority of melanomas contravenes these conventional parameters and displays unpredictable clinical behavior. Furthermore, lack of...

Prognostic role of maspin expression in melanoma: probably far from clinical use

“…found a correlation between maspin expression and nodular histotype, tumour thickness, mitotic rate and ulceration, even if this last study was performed exclusively on TMA specimens. Furthermore, they suggested maspin nuclear expression to be a negative prognostic parameter that seems conflicting with our results, as we only observed a maspin cytoplasmic expression. This opens a relevant query: could TMA be considered fully representative of an entire melanoma lesion?…”

“…Argon et al 5 studied block sampling of gallbladders, but specifically and only compared a longitudinal sampling technique (335 gallbladders) with a three-section sampling technique (273 gallbladders). Before that, Duarte et al 6 completely blocked 162 gallbladders, but focused on dysplasia and metaplasia, and only studied a Chilean population -that is recognized to harbour a much higher incidence of gallbladder neoplasia. 7 Therefore, this author remains unaware of any previous study of European populations that has systematically recorded the extent of different pathological findings (including inflammatory changes) at different sites of a non-tumorous gallbladder.…”

“…Desmin is a muscle-specific intermediate filament that is encoded by a gene (DES) assigned to human chromosome 2q35. 6 The aberrant desmin expression in this case might have occurred because of switching on of inactivated DES by an abnormality of the gene that regulates expression of the molecule. Although the cytogenetic profile of our case included add(2)(q21), but not an abnormality involving 2q35, it is possible that submicroscopic abnormalities involving DES or its locus control regions may be present.…”

5 protein-based signature for resectable lung squamous cell carcinoma improves the prognostic performance of the TNM staging

“…One of the advantages of IHC is that it allows the assessment of protein levels in specific subcellular compartments. It is well established that protein subcellular localisation has profound functional and prognostic effects for a large number of proteins 32. Together with the development of automatic programmes to quantify the staining, the experience in different fields supports the fact that new protein-based signatures may be easily implemented into the clinical practice in the near future.…”

Biomarkers in Malignant Melanoma: Recent Trends and Critical Perspective

“…Some attention also has been paid to other protease inhibitors, namely, maspin (serpinB5) and serpinB1, which both are members of the serine protease inhibitor superfamily. Loss of melanoma maspin has been suggested to contribute to disease progression and metastatic dissemination, but this subject is of controversial debate (41,42). SerpinB1 has been suggested as an indicator of chemotherapy response.…”