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. 2011 Apr 26;104(9):1418-25.
doi: 10.1038/bjc.2011.109. Epub 2011 Apr 5.

Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients

E Bignotti  1 , M Ragnoli, L Zanotti, S Calza, M Falchetti, S Lonardi, S Bergamelli, E Bandiera, R A Tassi, C Romani, P Todeschini, F E Odicino, F Facchetti, S Pecorelli, A Ravaggi
Affiliations

Diagnostic and prognostic impact of serum HE4 detection in endometrial carcinoma patients

E Bignotti et al. Br J Cancer. .

Abstract

Background: To date, no good marker for screening or disease monitoring of endometrial cancer (EC) is available. The aims of this study were to investigate HE4 gene, protein expression and serum HE4 (sHE4) levels in a panel of ECs and normal endometria (NEs) and to correlate sHE4 with patient clinicopathological characteristics and prognosis.

Methods: Using quantitative real-time PCR we tested 46 ECs and 20 NEs for HE4 gene expression. Protein expression was analysed by immunohistochemistry on tissue microarrays in 153 ECs and 33 NEs. Pre-operative serum samples from 138 EC and 76 NE patients were analysed with HE4-EIA assay. Association between sHE4 and patient clinicopathological characteristics or outcome was evaluated.

Results: Protein and HE4 gene were significantly upregulated in EC tissues and sera, compared with controls. High sHE4 levels were significantly associated with worse EC clinical characteristics. By univariate survival analysis, high sHE4 levels significantly correlated with decreased overall survival, progression-free survival and disease-free survival, retaining their independent prognostic value on the poorly differentiated EC cohort.

Conclusion: We demonstrate, for the first time, that high sHE4 levels correlates with an aggressive EC phenotype and may constitute an independent prognostic factor for poorly differentiated-ECs. Determination of sHE4 could be clinically useful in identifying high-risk EC patients for a more aggressive adjuvant therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
HE4 mRNA expression in endometrial carcinoma (EC) compared with normal endometrial tissues (NE). The figure shows the box plot of the relative quantification values in Log scale. As shown, HE4 mRNA expression was significantly higher in EC compared with NE patients (P<0.0001).
Figure 2
Figure 2
Representative immunohistochemical staining for HE4 in tissue microarrays of normal endometria (normal) and endometrial carcinomas (G1, G2 and G3). Normal tissues show predominantly a weak immunoreactivity for HE4 (mostly 1+), whereas G1, G2 and G3 endometrial carcinomas are mainly scored 3+, 2+ and 0/1+, respectively. Magnification: × 100; scale bar length: 200 micron.
Figure 3
Figure 3
Box plots showing serum HE4 (sHE4) levels in controls with normal endometrium (NE) and in endometrial cancer patients, represented according to differentiation grade (A) and to FIGO stage (B).
Figure 4
Figure 4
Kaplan–Meier survival curves for EC patients according to sHE4 levels on the entire patient cohort (A, overall survival; B, progression-free survival; C, disease-free survival) and on poorly differentiated subgroup of EC patients (D, overall survival; E, progression-free survival; F, disease-free survival). P-values refer to the comparison between high vs low tertile, except for C, in which medium vs low tertile shows to be significant.
See this image and copyright information in PMC

References

    1. Amant F, Moerman P, Neven P, Timmerman D, Van Limbergen E, Vergote I (2005) Endometrial cancer. Lancet 366(9484): 491–505 - PubMed
    1. Anastasi E, Marchei GG, Viggiani V, Gennarini G, Frati L, Reale MG (2010) HE4: a new potential early biomarker for the recurrence of ovarian cancer. Tumour Biol 31(2): 113–119 - PubMed
    1. Bignotti E, Tassi RA, Calza S, Ravaggi A, Romani C, Rossi E, Falchetti M, Odicino FE, Pecorelli S, Santin AD (2006) Differential gene expression profiles between tumor biopsies and short-term primary cultures of ovarian serous carcinomas: identification of novel molecular biomarkers for early diagnosis and therapy. Gynecol Oncol 103(2): 405–416 - PubMed
    1. Bingle L, Singleton V, Bingle CD (2002) The putative ovarian tumour marker gene HE4 (WFDC2), is expressed in normal tissues and undergoes complex alternative splicing to yield multiple protein isoforms. Oncogene 21(17): 2768–2773 - PubMed
    1. Bokhman JV (1983) Two pathogenetic types of endometrial carcinoma. Gynecol Oncol 15: 10–17 - PubMed

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