Overexpression of Cripto and its prognostic significance in breast cancer: A study with long-term survival

Gong, Y.P.; Yarrow, P.M.; Carmalt, H.L.; Kwun, S.Y.; Kennedy, C.W.; Lin, B.P.C.; Xing, P.X.; Gillett, D.J.

doi:10.1016/j.ejso.2006.10.014

« Previous Next »European Journal of Surgical Oncology
Volume 33, Issue 4 , Pages 438-443, May 2007

Overexpression of Cripto and its prognostic significance in breast cancer: A study with long-term survival

Y.P. Gong
- Department of Breast Endocrine Surgery, Concord Repatriation General Hospital, Hospital Road, Concord NSW 2137, Australia
- Permanent address: Department of Breast Surgery, Hubei Cancer Hospital, South Zhuodaoquan Road, Wuhan, Hubei 430079, People's Republic of China.
P.M. Yarrow
- Department of Anatomical Pathology, Concord Repatriation General Hospital, Australia
H.L. Carmalt
- Department of Breast Endocrine Surgery, Concord Repatriation General Hospital, Hospital Road, Concord NSW 2137, Australia
- The Strathfield Breast Centre, 3 Everton Road, Strathfield NSW 2135, Australia
- Corresponding author. The Strathfield Breast Centre, 3 Everton Road, Strathfield NSW 2135, Australia. Tel.: +61 2 97473789; fax: +61 2 97453714.
S.Y. Kwun
- Department of Anatomical Pathology, Concord Repatriation General Hospital, Australia
C.W. Kennedy
- The Strathfield Breast Centre, 3 Everton Road, Strathfield NSW 2135, Australia
B.P.C. Lin
- Department of Anatomical Pathology, Concord Repatriation General Hospital, Australia
P.X. Xing
- The Cancer Immunotherapy Laboratory, Burnet Institute, Studley Road, Heidelberg VIC 3084, Australia
D.J. Gillett
- Department of Breast Endocrine Surgery, Concord Repatriation General Hospital, Hospital Road, Concord NSW 2137, Australia
- The Strathfield Breast Centre, 3 Everton Road, Strathfield NSW 2135, Australia

Accepted 9 October 2006.

Abstract

Introduction

Cripto is a founding member of the EGF-CFC family, and plays an important role in tumourigenesis, tumour cell proliferation and migration. We aimed to determine the significance of Cripto expression on the survival of patients with breast cancer.

Methods

Immunohistochemical detection of Cripto was performed by using mAb C13 on 120 formalin-fixed paraffin-embedded breast tumour specimens in tissue microarrays. This cohort comprises a series of 120 patients with primary operable breast cancer diagnosed between 1989 and 1995, retrieved from the Concord Repatriation General Hospital breast carcinoma database.

Results

Using a cutoff value of 80%, Cripto overexpressed in 57 of the 120 (47.5%) patients. We found significant associations between overexpression of Cripto and the Nottingham Prognostic Index (NPI, p<0.01), histological grade (p<0.01), pathological tumour type (p=0.04), PR (p=0.02) as well as Ki-67 (p=0.02). Univariate analysis reveals that there is a significant correlation between overexpression of Cripto and survival (p=0.0003). Cox regression analysis indicates that the overexpression of Cripto is an independent prognostic factor in breast cancer (HR 2.79, 95%CI 1.20–6.50).

Conclusion

The unique epitope recognized by mAb C13 is overexpressed on breast tumour tissues. In this series of invasive breast cancers, overexpression of Cripto was more often found in high grade and poor prognosis tumours compared to low grade and good prognosis breast cancers. Moreover, overexpression of Cripto was significantly associated with decreased patient survival.

Keywords: Breast cancer, Cripto, Prognosis