Geburtshilfe Frauenheilkd 2016; 76(04): 427-441
DOI: 10.1055/s-0036-1580661
C. Gynäkologie und gynäkologische Onkologie
Georg Thieme Verlag KG Stuttgart · New York

Cytoplasmic GPER predicts excellent overall and progression free survival in early stage cervical cancer

K Friese
1   Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München, München
2   Klinik Bad Trissl GmbH, Oberaudorf
,
C Kuhn
1   Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München, München
,
S Mahner
1   Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München, München
,
U Jeschke
1   Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München, München
,
S Heublein
1   Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe, Klinikum der Universität München, München
3   Universitäts-Frauenklinik, Universitäts-Klinikum Heidelberg, Heidelberg
› Author Affiliations
Further Information

Publication History

Publication Date:
26 April 2016 (online)

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Background:

Estrogen signalling is transduced via both a genomic and a non-genomic route. While genomic i.e. ER alpha mediated signals are closely associated with HPV induced carcinogenesis in cervical cancer, the role of non-genomic estrogen signalling i.e. mediated by the G-Protein coupled Estrogen Receptor (GPER) remains to be rather elusive. So far – to the best of our knowledge – no data exist upon GPER expression in cervical cancer. Hence the aim of the current study was to determine GPER immunopositivity as well as its potential association with clinico-pathological parameters in a cohort of cervical cancer patients.

Material and Methods:

GPER was determined in tissue collected from 156 patients that had undergone surgery due to cervical cancer between 1993 and 2002. Most patients were diagnosed a tumour staged higher than FIGO I (93/156; 59.6%), larger than pT1 (132/156; 84.0%), and graded higher than 1 (140/156, 89.7%). Mean overall survival (OS) was 15.4 years; mean progression free survival (PFS) was 13.8 years.

Results:

GPER was found to be expressed in different subcellular patterns. Cytoplasmic GPER staining (GPERcyt) was detected in 129/156 (82.7%) cases and 116/156 (74.4%) cases presented with membrane GPER (GPERmem) staining. The minority (14/156; 9.0%) of patients were classified as GPER completely negative, while most tissue samples (101/156; 64.7%) were scored as double positive (GPERcyt + GPERmem). Though some correlations of GPER and HPV indicators (viral protein E6, p16, p53) were detected, neither GPERcyt nor GPERmem were associated with pathological parameters. More important, immunopositivity of GPERcyt was closely correlated with favourable OS (univariate: p = 0.01, multivariate: p = 0.037) as well as PFS (univariate: p = 0.001, multivariate: p = 0.008) in cervical cancer of early stage (FIGO I).

Conclusion:

GPERcyt was found to predict favourable OS and PFS in cervical cancer staged as FIGO I. Interestingly, there is initial evidence that SERMs (e.g. Raloxifene) may prevent relapse of cervical cancer in mice. Since SERMs block ER alpha but activate GPER, the effect of Raloxifene on relapse of cervical cancer may – at least to some extend – be dependent on GPER.