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. 2008 Feb 26;98(4):845-51.
doi: 10.1038/sj.bjc.6604216. Epub 2008 Jan 29.

Coexpression of EphB4 and ephrinB2 in tumour advancement of ovarian cancers

S M Alam  1 , J Fujimoto, I Jahan, E Sato, T Tamaya
Affiliations

Coexpression of EphB4 and ephrinB2 in tumour advancement of ovarian cancers

S M Alam et al. Br J Cancer. .

Abstract

EphB4 and ephrinB2 expressions in ovarian cancers were studied to analyse EphB4/ephrinB2 functions against clinical backgrounds. EphB4 and ephrinB2 were dominantly localised in ovarian cancer cells of all cases studied. Both the histoscores and mRNA levels of EphB4 and ephrinB2 significantly increased with clinical stages (I<II<III<IV, P<0.001) in ovarian cancers, although there was no significant difference in EphB4 and ephrinB2 histoscores or in mRNA levels according to histopathological types. EphB4 as well as ephrinB2 histoscores in cancer cells correlated with the corresponding mRNA levels in each case (EphB4, P<0.001; ephrinB2, P<0.001). The 24-month survival rates of the 36 patients with high EphB4 and ephrinB2 expression were poor (25 and 27%, respectively), while for the other 36 patients with low EphB4 and ephrinB2 expression, they were significantly higher (68 and 64%, respectively). Therefore, EphB4/ephrinB2 may function in tumour advancement and coexpression of the Eph/ephrin system may potentiate tumour progression leading to poor survival. Thus, EphB4/ephrinB2 can be recognised as a novel prognostic indicator in the primary tumours of ovarian cancers.

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Figures

Figure 1
Figure 1
Immunohistochemical staining for EphB4 and ephrinB2 in ovarian cancers (original magnification × 200). A representative case of clear cell carcinoma of the right ovary is shown. Rabbit EphB4 and ephrinB2 antibodies (Santa Cruz) were used at dilutions of 1 : 100 and 1 : 75, respectively, as primary antibodies. Dark brown staining represents positive for EphB4 and ephrinB2 antigen. Bars=100 μm.
Figure 2
Figure 2
Correlation of EphB4 and ephrinB2 histoscores with mRNA levels in ovarian cancers. Correlation between EphB4 histoscores in cancer cells with mRNA levels and ephrinB2 histoscores in cancer cells with mRNA levels in ovarian cancers is shown. Both EphB4 and ephrinB2 histoscores and mRNA levels were determined by immunohistochemistry and real-time RT–PCR, respectively. Each level is the mean±s.d. of nine determinations.
Figure 3
Figure 3
EphB4 and ephrinB2 histoscores and mRNA levels in ovarian cancers classified according to clinical stages. The histoscores and mRNA levels of EphB4 and ephrinB2 were determined by immunohistochemistry and real-time RT–PCR, respectively. Clinical stages of ovarian cancer were assessed according to the FIGO classification. Each level is the mean±s.d. of nine determinations. Alive and dead cases are numbered in open circles and closed circles, respectively; *P<0.05; **P<0.001.
Figure 4
Figure 4
EphB4 and ephrinB2 histoscores and mRNA levels in ovarian cancers classified according to histopathological types. SPCY, serous papillary cystadenocarcinoma; SCY, serous cystadenocarcinoma; MCY, mucinous cystadenocarcinoma; C, clear cell carcinoma; E, endometrioid adenocarcinoma. Alive and dead cases are numbered in open circles and closed circles, respectively. Each level is the mean±s.d. of nine determinations.
Figure 5
Figure 5
Survival rates after curative resection for ovarian cancers. Patient prognosis was analysed with a 24-month survival rate. High EphB4, histoscores >170 and mRNA levels >4.0 × 105 DNA copy per μg total RNA, n=36, solid line; low EphB4, histoscores <170 and mRNA levels <4.0 × 105 DNA copy per μg total RNA, n=36, dotted line in the upper panel. High ephrinB2, histoscores >192 and mRNA levels >3.9 × 106 DNA copy per μg total RNA, n=36, solid line; low ephrinB2, histoscores <192 and mRNA levels <3.9 × 106 DNA copy per μg total RNA, n=36, dotted line in the lower panel.
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References

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