1170P - Prognostic and predictive significance of pharmacogenetic analysis in patients with carcinomas of unknown primary (CAUP)

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Carcinoma of Unknown Primary Site
Translational Research
Presenter Chara Papadaki
Authors C. Papadaki1, G. Pentheroudakis2, A. Cervantes Ruiperez3, E. Lagoudaki4, D. Petrakis5, J. Souglakos6, E.R. Braun7, V. Georgoulias8, D. Mavroudis6, N. Pavlidis9
  • 1Laboratory Of Tumor Cell Biology, School of Medicine, University of Crete, 71110 - Heraklion/GR
  • 2Oncology Secretariat B Building Ground Floor, University General Hospital of Ioannina, 45500 - Ioannina/GR
  • 3Serv. Hematologia Y Oncologia Medica, Hospital Clinico Universitario de Valencia, ES-46010 - Valencia/ES
  • 4Laboratory Of Pathology, School of Medicine, University of Crete, 71110 - Heraklion/GR
  • 5Medical Oncology, University General Hospital of Ioannina, 45500 - Ioannina/GR
  • 6Medical Oncology, University General Hospital of Heraklion, 71110 - Crete/GR
  • 7Hematology And Medical Oncology, INCLIVA University of Valencia, 46010 - Valencia/ES
  • 8Medical Oncology, University Hospital of Heraklion, 71110 - Heraklion/GR
  • 9University of Ioannina, GR-455 00 - Ioannina/GR

Abstract

Purpose

To investigate the prognostic/predictive significance of the expression of BRCA1, ERCC1, RRM1, TOPO-I, TOPO-IIa, TOPO-IIb, TXR1 TYMS and HIF1a mRNA in patients with Carcinomas of Unknown Primary (CaUP).

Material and methods

Ninety-three patients with CaUP and available tumoral samples diagnosed in three institutions were included in the study. The mRNA levels of the target genes were determined by quantitative real-time PCR from microdissected cells derived from patients' tumoral specimens. �-actin and PGK1 were used as reference genes.

Results

Successful amplification of at least one gene was achieved in all samples. BRCA1, ERCC1, HIF1a and TXR1 were amplified in all samples, while RRM1, TOPO-I, TOPO-IIa, TOPO-IIb were amplified in 88 samples and TYMS in 86 of them. Patients' characteristics were: median age 68 (28-84) years; 53 (57%) males; ECOG-PS 0 in 23 (25%), 1 in 33 (35%) and ≥ 2 in 37 (40%) patients. The histological type was: 47 (50%) adenocarcinomas, 18 (19%) squamous cell carcinomas, 14 (15%) undifferentiated carcinomas, 8 (9%) carcinomas with neuroendocrine features and 6 (6%) clear cell carcinomas. Forty-one (47%) patients received a platinum analog as 1st line treatment, while 21 (24%) were treated with taxane-based chemotherapy. Patients with high ERCC1 mRNA levels presented increased median overall survival compared with those with low ERCC1 expression (mOS: 16.5 versus 8.3 months; p = 0.034). Also, high compared to low expression of TXR1 or TOPO-I was significantly correlated with decreased survival (4.5 months vs. 22.6 months; p = 0.015 and 5.9 months vs. 16.5 months; p = 0.042, respectively). A statistical trend for increased survival was also observed in patients with low HIF1a expression (p = 0.07), while the expression of the other genes did not show significant prognostic correlation. No predictive significance of any gene was observed in patients treated with a platinum analog.

Conclusions

The ERCC1, TXR1, TOPO-IA and HIF1a expression may be used as prognostic markers in patients with CaUP. The predictive significance of these genes was not confirmed in the small subgroup of patients treated with platinum analogs.

Disclosure

All authors have declared no conflicts of interest.