Oncotarget

Research Papers:

Cisplatin fails to induce puma mediated apoptosis in mucosal melanomas

Marie Kristin Fritsche _, Veronika Metzler, Karen Becker, Christian Plettenberg, Clemens Heiser, Benedikt Hofauer and Andreas Knopf

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Oncotarget. 2015; 6:9887-9896. https://doi.org/10.18632/oncotarget.3195

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Abstract

Marie Kristin Fritsche1, Veronika Metzler1, Karen Becker2, Christian Plettenberg3, Clemens Heiser1, Benedikt Hofauer1, Andreas Knopf1

1Technische Universität München, Hals-Nasen-Ohrenklinik und Poliklinik, 81675 München, Germany

2Universität München, Institut für Allgemeine Pathologie und Pathologische Anatomie, 81675 München, Germany

3Heinrich Heine Universität Düsseldorf, Hals-Nasen-Ohrenklinik, 40225 Düsseldorf, Germany

Correspondence to:

Marie Kristin Fritsche, e-mail: [email protected]

Keywords: melanoma, sinonasal, survival, p53, cell-cycle

Received: December 18, 2014     Accepted: January 23, 2015     Published: March 26, 2015

ABSTRACT

Objectives

Mucosal melanomas (MM) are aggressive subtypes of common melanomas. It remains unclear whether limitations in their resectability or their distinctive molecular mechanisms are responsible for the aggressive phenotype.

Methods

In total, 112 patients with cutaneous melanomas (CM) and 27 patients with MM were included. Clinical parameters were analysed using Chi square, Fisher exact and student’s t-test. Survival rates were calculated by Kaplan–Meier. Analysis of p53, p21, Mdm2, Hipk2, Gadd45, Puma, Bax, Casp9 and Cdk1 via quantitative PCR and immunohistochemistry (IHC) was performed. TP53 induction after cisplatin treatment was analysed in 10 cell lines (melanocytes, four MM and five CM) using western blot (WB) and qPCR.

Results

The overall/recurrence-free survival differed significantly between MM (40 months and 30 months) and CM (90 months and 107 months; p < 0.001). IHC and WB confirmed high p53 expression in all melanomas. Hipk2 and Gadd45 showed significantly higher expressions in CM (p < 0.005; p = 0.004). QPCR and WB of wild-type cell lines demonstrated no differences for p53, p21, Mdm2, Bax and Casp9. WB failed to detect Puma in MM, while Cdk1 regulation occurred exclusively in MM.

Conclusions

The aggressive phenotype of MM did not appear to be due to differential expressions of p53, p21, Mdm2, Bax or Casp9. A non-functional apoptosis in MM may have further clinical implications.


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