Loss of IFNγ Receptor Is an Independent Prognostic Factor in Ovarian Cancer

• Published in: Clinical cancer research Vol. 13; no. 14; pp. 4139 - 4145
• Main Authors: DUNCAN, Timothy J, ROLLAND, Phil, DEEN, Suha, SCOTT, Ian V, LIU, David T. Y, SPENDLOVE, Ian, DURRANT, Lindy G
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.07.2007
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Female; Female genital diseases; Gynecologic cancers: ovarian; Gynecology. Andrology. Obstetrics; Humans; IFNγ; IFNγ receptor; Immunoediting; Interferon gamma Receptor; Medical sciences; Middle Aged; Neoplasm Staging; Oligonucleotide Array Sequence Analysis; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Pharmacology. Drug treatments; Prognosis; Receptors, Interferon - deficiency; Receptors, Interferon - genetics; Survival Analysis; Tumors; Ovarian diseases; Prognosis; Ovary cancer; Malignant tumor; Female genital diseases; Gamma interferon; Biological receptor
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-06-2833

Purpose: There is evidence that IFNγ plays an important role in ovarian cancer development. IFNγ produces numerous antitumor effects and it may be evasion of these effects which allows tumor progression. We postulate that genetic instability in tumor cells may lead to modulation of expression of the IFNγ receptor, thus leading to altered tumor biology and patient prognosis. This hypothesis would support the theory of immunoediting in ovarian cancer. Experimental Design: Using tissue microarray technology of 339 primary ovarian cancers, the expression of IFNγ receptor was assessed immunohistochemically. Coupled to a comprehensive database of clinicopathologic variables, its effect on these factors was studied. Results: Tumors expressing high levels of IFNγ receptor had significantly improved survival ( P = 0.017) compared with tumors expressing low levels of the receptor; this was also seen with complete receptor loss ( P = 0.014). Factors shown to predict prognosis independently of each other were the following: age, International Federation of Gynecologists and Obstetricians stage, and the absence of macroscopic disease after surgery. The level of IFNγ receptor expression and complete receptor loss were independently predictive of prognosis on multivariate analysis. There was no correlation between receptor status and any of the standard clinicopathologic variables. Conclusions: Loss of IFNγ receptor independently predicts poor prognosis in ovarian cancer. Loss of receptor expression may be responsible for the limited success in the therapeutic use of IFNγ in ovarian cancer trials and highlights a subgroup of high expressing IFNγ receptor tumors which are more likely to be susceptible to such treatments.