REPORT
AAA+ ATPases Reptin and Pontin as potential diagnostic and prognostic
biomarkers in salivary gland cancer - a short report
Jan-Henrik Mikesch
1
&
Wolfgang Hartmann
2
&
Linus Angenendt
1
&
Otmar Huber
3
&
Christoph Schliemann
1
&
Maria Francisca Arteaga
1
&
Eva Wardelmann
2
&
Claudia Rudack
4
&
Wolfgang E. Berdel
1
&
Markus Stenner
4
&
Inga Grünewald
2
Accepted: 9 May 2018
#
International Society for Cellular Oncology 2018
Abstract
Purpose Salivary gland cancer (SGC) is a rare and heterogeneous disease with significant differences in recurrence and metas-
tasis characteristics. As yet, little is known about the mechanisms underlying the initiation and/or progression of these diverse
tumors. In recent years, the AAA+ ATPase family members Pontin (RuvBL1, Tip49a) and Reptin (RuvBL2, Tip49b) have been
implicated in various processes, including transcription regulation, chromatin remodeling and DNA damage repair, that are
frequently deregulated in cancer. The aim of this study was to assess the clinical and functional significance of Reptin and
Pontin expression in SGC.
Methods Immunohistochemical staining of Pontin, Reptin, β-catenin, Cyclin D1, TP53 and MIB-1 was performed on a collec-
tion of 94 SGC tumor samples comprising 13 different histological subtypes using tissue microarrays.
Results We found that Reptin and Pontin were expressed in the majority of SGC samples across all histological subtypes. Patients
with a high Reptin expression showed a significantly inferior 5-year overall survival rate compared to patients with a low Reptin
expression (47.7% versus 78.3%; p = 0.033), whereas no such difference was observed for Pontin. A high Reptin expression
strongly correlated with a high expression of the proliferation marker MIB-1 (p = 0.003), the cell cycle regulator Cyclin D1 (p =
0.006), accumulation of TP53 as a surrogate p53 mutation marker (p = 0.042) and cytoplasmic β-catenin expression (p =0.002).
Increased Pontin expression was found to significantly correlate with both cytoplasmic and nuclear β-catenin expression (p =
0.037 and p = 0.018, respectively), which is indicative for its oncogenic function.
Conclusions Our results suggest a role of Reptin and Pontin in SGC tumor progression and/or patient survival. Therefore, SGC
patients exhibiting a high Reptin expression may benefit from more aggressive therapeutic regimens. Future studies should
clarify whether such patients may be considered for more radical surgery, extended adjuvant therapy and/or targeted therapy.
Keywords Salivary gland cancer
.
AAA+ ATPases
.
Reptin
.
Pontin
.
β-catenin
1 Introduction
Salivary gland cancer (SGC) accounts for 3–6% of all head
and neck cancers [1] and constitutes a heterogeneous group of
malignant tumors originating from diverse anatomical sites,
with various histological appearances and significant differ-
ences in their propensities to develop recurrences and metas-
tases [2, 3]. The WHO classification system distinguishes 24
histological entities of malignant SGC tumors. Although stud-
ies dealing with the pathogenesis of some of the SGC sub-
typeshavebeenreported[4–7], currently little is known about
the mechanisms driving the initiation and/or progression of
these diverse tumors. Primary surgery is the standard therapy
for SGC whenever feasible, and adjuvant radiotherapy is
* Jan-Henrik Mikesch
Jan-Henrik.Mikesch@ukmuenster.de
* Inga Grünewald
Inga.Gruenewald@ukmuenster.de
1
Department of Medicine A, University Hospital of Münster,
Albert-Schweitzer-Campus 1, 48149 Münster, Germany
2
Gerhard-Domagk-Institute for Pathology, University Hospital of
Münster, Albert Schweitzer Campus 1 D17,
48149 Münster, Germany
3
Department of Biochemistry II, Jena University Hospital,
Nonnenplan 2, 07743 Jena, Germany
4
Department of Otorhinolaryngology, Head and Neck Surgery, School
of Medicine, University Hospital of Münster,
Kardinal-von-Galen-Ring 10, 48149 Münster, Germany
Cellular Oncology
https://doi.org/10.1007/s13402-018-0382-8
@Phil_Robichaud
@deepthiw
@JoseServera