830P - The predictive and prognostic role of o6-methylguanine-DNA methyltransferase (MGMT) and tissue transglutaminase-2 (TGASE-2) in metastatic renal cell...

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Renal Cell Cancer
Translational Research
Presenter Didem Tunali
Authors D. Tunali1, B. Sarsık2, R. Durusoy3, S. Şen2, E. Gökmen4
  • 1Medical Oncology, Ege University Medical School, 35100 - Izmir/TR
  • 2Department Of Pathology, Ege University Medical School, IZMIR/TR
  • 3Department Of Public Health, Ege University Medical School, IZMIR/TR
  • 4Department Of Medical Oncology, Ege University Medical School, IZMIR/TR

Abstract

Background

Altough anti-angiogenic drugs are widely used in mRCC, the predictive markers for these agents cannot be well defined yet. MGMT is recently shown to be anti-angiogenic and responsible for the anti-proliferative effect of sunitinib in glioblastome cell lines. In preclinical studies, MGMT positive cells demonstrate high sVEGFR-1/VEGFA ratio, increased VEGFR-1 and decreased VEGFR-2.

TGase-2 is known to be responsible for drug resistance, cell proliferation, migration and angiogenesis. In vitro studies showed that TGase-2 inhibits VHL and this leads to increase of HIF-1α and IGF-1R.

Objective

To investigate the predictive and prognostic role of MGMT and TGase-2 in mRCC patients who were treated with sunitinib.

Methods

We analyzed 82 RCC patients retrospectively. 43 of 82 survive without recurrence (non-metastatic group), 39 of 82 were already metastatic at the diagnosis or had metastasis during follow up (metastatic group). Expression of MGMT and TGase-2 proteins were assessed by immunohistochemical (IHC) staining in tissue samples.

In the metastatic group, all patients received sunitinib as anti-angiogenic therapy and the overall survival (OS) analysis of these patients were performed according to time of sunitinib initiation. OS analysis of the entire group (metastatic and non-metastatic) were performed according to the time of diagnosis.

Results

In the metastatic group (n = 39), the ones with low MGMT had median OS of 30 months while ones with high MGMT had median OS of 47 months (p = 0.498). The ones with low TGase-2 had mean OS of 35.2 months while ones with high TGase-2 had mean OS of 27.9 months (p = 0.366).

In the entire group, the ones with low MGMT had mean OS of 115 months while ones with high MGMT had median OS of 189 months (p = 0.498). The ones with low TGase-2 had mean OS of 212 months while ones with high TGase-2 had mean OS of 133 months (p = 0.281).

Conclusions

Higher MGMT and lower TGase-2 may be predictors of good response to sunitinib. Independent of the treatment, in the entire group the ones with higher MGMT and lower TGase-2 have better survival. All these results are not statistically significant.

Disclosure

All authors have declared no conflicts of interest.