European Journal of Clinical Investigation

Volume 45, Issue 11 pp. 1145-1152

Original Article

Prognostic significance of WNT and hedgehog pathway activation markers in cancer of unknown primary

George Fotopoulos,

George Fotopoulos

Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece

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Anna Gousia,

Anna Gousia

Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece

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Eleni Bareta,

Eleni Bareta

Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece

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Epameinondas Koumpis,

Epameinondas Koumpis

Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece

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Sofia Chrisafi,

Sofia Chrisafi

Department of Medical Oncology, Medical School, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Matthaios Bobos,

Matthaios Bobos

Department of Pathology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Vassiliki Malamou-Mitsi,

Vassiliki Malamou-Mitsi

Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece

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George Fountzilas,

George Fountzilas

Department of Medical Oncology, Medical School, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Nicholas Pavlidis,

Nicholas Pavlidis

Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece

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George Pentheroudakis,

Corresponding Author

George Pentheroudakis

Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece

Correspondence to: George Pentheroudakis, Medical School, University of Ioannina, Niarxou Avenue, 45500 Ioannina, Greece. Tel/fax: +30 2651099394; e-mail: [email protected]Search for more papers by this author

George Fotopoulos,

George Fotopoulos

Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece

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Anna Gousia,

Anna Gousia

Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece

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Eleni Bareta,

Eleni Bareta

Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece

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Epameinondas Koumpis,

Epameinondas Koumpis

Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece

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Sofia Chrisafi,

Sofia Chrisafi

Department of Medical Oncology, Medical School, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Matthaios Bobos,

Matthaios Bobos

Department of Pathology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Vassiliki Malamou-Mitsi,

Vassiliki Malamou-Mitsi

Department of Pathology, Medical School, University of Ioannina, Ioannina, Greece

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George Fountzilas,

George Fountzilas

Department of Medical Oncology, Medical School, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Nicholas Pavlidis,

Nicholas Pavlidis

Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece

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George Pentheroudakis,

Corresponding Author

George Pentheroudakis

Department of Medical Oncology, Medical School, University of Ioannina, Ioannina, Greece

First published: 13 August 2015

https://doi.org/10.1111/eci.12518

Citations: 4

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Abstract

Background

Cancer of unknown primary (CUP) possesses distinct biology and peculiar natural history, in which the roles of the winged and hedgehog signalling pathways are unclear.

Materials and methods

We constructed tissue microarrays and studied the immunohistochemical (IHC) expression of β-catenin, smoothened (SMO) and the transcription factors TCF, LEF, GLI1 in 87 CUP cases for prognostic significance.

Results

A low rate of IHC expression of proteins was seen, the cut-off used being any expression in ≥ 1% of tumour cells. At univariate analysis, only nuclear IHC SMO expression displayed a statistically significant association with favourable outcome [median Overall survival (OS) of 19 months in SMO-positive vs. 12 months in SMO-negative cases, P = 0·01]. An activated Wnt pathway, defined as IHC expression of any of nuclear β-catenin, TCF and LEF, was significantly associated with favourable progression free survival (median 9 vs. 5 months, P = 0·037) and OS (median 19 vs. 13 months, P = 0·04). This prognostic impact on OS was mainly driven by nuclear expression of TCF and/or LEF (P = 0·03). No prognostic significance of the hedgehog pathway activation status, defined as IHC expression of SMO or nuclear GLI1, could be established. A favourable prognostic impact of the concurrent activation of both pathways was observed. A trend for association of activated Wnt with response to chemotherapy (responders 67% among activated Wnt cases vs. 35% among nonactivated Wnt cases, P = 0·07) was observed in CUP adenocarcinomas.

Conclusions

Activation of the Wnt pathway was a positive prognostic factor in a small CUP series, possibly via enhanced chemosensitivity. Independent validation is warranted.

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Citing Literature

Volume45, Issue11

November 2015

Pages 1145-1152

Prognostic significance of WNT and hedgehog pathway activation markers in cancer of unknown primary

Abstract

Background

Materials and methods

Results

Conclusions

References

Citing Literature

References

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Prognostic significance of WNT and hedgehog pathway activation markers in cancer of unknown primary

Abstract

Background

Materials and methods

Results

Conclusions

References

Citing Literature

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