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However, additional analysis suggested that three proteins (C3, C4A/C4B and
APOA1) have a stronger association with ILD than the other proteins tested.
Conclusions: We were unable to conclude from the results of this study that any
promising serum protein markers for predicting ILD had been identified. However,
C3, C4A/C4B and APOA1 were suggested to be worth further investigation.
Disclosure: N. Katakami: corporate-sponsored research (Chugai Pharmaceutical
Company). S. Atagi: corporate-sponsored research (Chugai Pharmaceutical Company).
H. Yoshioka: corporate-sponsored research (Chugai Pharmaceutical Company). M.
Fukuoka: other substantive relationships (Chugai, Astra Zeneca). A. Ogiwara:
corporate-sponsored research (Chugai, Astra Zeneka). M. Imai: M Imai is employee of
Chugai Pharmaceutical Co., Ltd. M. Ueda: M Ueda is employee of Chugai
Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.
233 PSF3 IS A NOVEL PROGNOSTIC BIOMARKER IN LUNG
ADENOCARCINOMA
D. Hokka, Y. Maniwa, S. Tane, S. Tauchi, W. Nishio, M. Yoshimura
Divisions of Thoracic Surgery, Department of Surgery, Kobe University Graduate
School of Medicine, Kobe, JAPAN
Background: PSF3 is a member of the highly evolutionarily conserved tetrameric
complex termed GINS, composed of SLD5, PSF1, PSF2, and PSF3. Previous studies
suggested that some GINS complex members are upregulated in cancer, but PSF3
expression in lung adenocarcinoma has not been investigated. The objective of the
current study was to elucidate the role of PSF3 in lung adenocarcinoma by
investigating clinical samples.
Methods: We investigated the expression of PSF3 in cancer epithelial cells
immunohistochemically in 125 consecutive resected cases of lung adenocarcinoma.
Results: Increased PSF3 expression was observed in 27 (21.6%) of the 125 cases.
PSF3 expression was found to be correlated significantly with some
clinicopathological factors. A univariate analysis and log–rank test indicated a
significant association between PSF3 expression and lower overall survival rate (P =
0.0001 and P < 0.0001, respectively). A multivariate analysis also indicated a
statistically significant association between increased PSF3 expression and lower
overall survival rate (hazard ratio, 5.2; P = 0.0027). In a subgroup analysis of only
stage I patients, increased PSF3 expression was also significantly associated with a
lower overall survival rate (P = 0.0008, log–rank test). Moreover, the Ki67 index level
was higher in the PSF3- positive group than in the negative group (P < 0.0001,
Mann–Whitney U-test).
Conclusion: The current results indicated that PSF3 is a novel prognostic biomarker
in lung adenocarcinoma.
Disclosure: All authors have declared no conflicts of interest.
234 MUTATIONS IN THE EPIDERMAL GROWTH FACTOR
RECEPTOR GENE IN NON-SMALL-CELL LUNG CANCER
PATIENTS AND EGFR SERUM LEVELS
E.Y. Romero-Ventosa 1 , M. Rodríguez Rodríguez 1 , S. Gonzalez Costas 1 ,
A. GonzÁlez-PiÑeiro 2 , S. Blanco-Prieto 3 , M. Páez de La Cadena 3 ,I.
Arias Santos 1 , B. Leboreiro Enriquez 1 , B. Bernardez Ferran 4 , E. Brozos 5
1 Farmacia Hospitalaria, Complejo Hospitalario Universitario de Vigo
(CHUVI)-Hospital Xeral-Cíes, Vigo, SPAIN, 2 Pathological Anatomy, Complejo
Hospitalario Universitario de Vigo (CHUVI)-Hospital Xeral-Cíes, Vigo, SPAIN,
3 Bioquímica, Genética E Inmunología, Universidad de Vigo, Vigo, SPAIN,
4 Farmacia Hospitalaria, Complejo Hospitalario Universitario de Santiago (CHUS),
Santiago, SPAIN, 5 Dept. of Medical Oncology, Complejo Hospitalario
Universitario de Santiagode Compostela Sergas, Santiago de Compostela,
SPAIN
Background: Determine the existing mutations in the epidermal growth factor
receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients and correlate
with survival. Also pretreatment EGFR serum levels were quantified and analyzed if
there were differences between patients with or without mutations.
Methods: From July 09 and July 11 serum samples were collected before starting
erlotinib. Serum levels of EGFR were quantified using an ELISA. Patients were
examined for mutations in tissue by EGFR Mutation Test Kit cobas. SPSS was used
to calculate overall survival (OS) and progression-free survival (PFS). Mann-Whitney
U test was used for comparison of EGFR serum level.
Results: 58 patients were studied but we obtained information of mutations in 34
patients. All variants were found in exons 18, 19 and 21 of EGFR. No mutation
was found in exon 20, only two polymorphisms. Of 32 patients analyzed, we
detected a total of 11 mutations (34.4%). In exon 19 we found 8 mutations
(del19) and affected 8 patients (72.7% mutations). In exon 21 we found two
mutations (L858R and L861Q), each in 1 patient (18.2% mutations). In exon 18,
G719X mutation was found in 1 patient (9.1% mutations). The remaining patients
(65.6%) were wild type. Patients wild type have a median OS of 5.4 months (95%
CI, 4.2 - 6.6) and mutated patients 12.6 months (95% CI, 4.7- 21.1); p = 0.033. In
terms of PFS, wild type patients have a median PFS of 2.8 months (95% CI: 2.0 -
3.6) and mutated 8.6 months (95% CI 2.0 - 15.1); p = 0.012. We determined
Annals of Oncology
serum levels of EGFR in 44 patients with a mean of 57.5 ng/mL. Of these
patients, 21 were wild type, 7 were mutated and 16 showed an unknown
mutational status. In wild type patients, the mean serum levels of EGFR was 57.8
ng/mL and in the mutant was 62.3 ng/mL.
Conclusion: Patients with EGFR gene mutation have a higher OS and PFS. No
differences were found in EGFR serum levels prior to erlotinib treatment between
wild type and mutated patients.
Disclosure: All authors have declared no conflicts of interest.
235 CORRELATION OF C609T POLYMORPHISM OF NADPH
QUINONE OXIDOREDUCTASE 1 AND HEMATOLOGICAL
TOXICITIES IN LUNG CANCER PATIENTS TREATED WITH
AMRUBICIN
M. Nagata 1 , T. Kimura 1 , T. Suzumura 1 , S. Kudoh 1 , K. Umekawa 1 , Y. Kira 2 ,
K. Matsuura 1 , T. Nakai 1 , S. Mitsuoka 1 , K. Hirata 1
1 Respiratory Medicine, Osaka City University, Osaka, JAPAN, 2 Department of
Central Laboratory, Osaka City University, Osaka, JAPAN
Background: Amrubicin hydrochloride (AMR) is a novel synthetic
aminoanthracycline derivative, that is metabolically activated to amrubicinol
(AMR-OH) by carbonyl reductase. The cytotoxic activity of AMR-OH is promising
for small cell lung cancer and considered as a key agent. NADPH Quinone
Oxidoreductase 1 (NQO1) is a cytosolic flavoprotein that metabolizes the quinone
structures contained in both AMR and AMR-OH. NQO1 expression genotyped
homozygous for minor alleles (T/T) was low compared with homozygous for major
alleles (C/C) or heterozygous (C/T). We hypothesized that NQO1 C609T
polymorphisms may relate to the AMR pharmacokinetics and clinical outcomes.
Methods: The patients with lung cancer received AMR at a dose of 30 or 40mg/m 2 /
day on day 1-3 at Osaka City University Hospital were enrolled. Plasma sampling
was performed at the time points of 24h after the third AMR injection. The
concentrations of AMR and AMR-OH were determined by HPLC method. NQO1
C609T polymorphism was assayed using real-time polymerase chain reaction
methods.
Results: A total of 35 patients were enrolled. The C/C, C/T, and T/T were observed
in 12 (34.3%), 16 (45.7%), and 7 (20%) patients, respectively. A dose of 30 mg/m 2
was administered to 19 patients, and 40mg/m 2 was administered to 16 patients. The
mean plasma concentrations of AMR-OH on day4 at a dose of 30mg/m 2 and 40mg/
m 2 were 11.02 ± 3.83 and 16.18 ± 6.17 ng/ml, respectively (p = 0.005). In patients
with AMR at a dose of 40mg/m 2 , the plasma concentrations of AMR-OH on day4
exhibited a tendency toward a relationship with NQO1 genotypes with values of C/C
20.5 ± 5.89, C/T 15.9 ± 5.43, and T/T 11.2 ± 4.47ng/ml (p = 0.066). The C/C was
related to decrease changes in WBC, hemoglobin, and platelet counts (p = 0.01, p =
0.03, and p = 0.0005, respectively). No significant correlations were observed between
NQO1 genotypes and clinical outcomes at a dose of 30mg/m 2 .
Conclusions: NQO1 C609T polymorphism had a tendency of correlation with the
plasma concentrations of AMR-OH, and thereby had significant correlations with
hematologic toxicities. NQO1 genotype appears to be the candidate biomarker of
hematological toxicities of AMR treatment at a dose of 40mg/m 2 .
Disclosure: All authors have declared no conflicts of interest.
236 POLYCYSTINS 1 AND 2 AS NOVEL PROGNOSTIC MARKERS
IN COLORECTAL CANCER
A.N. Gargalionis 1 , G. Dalagiorgou 1 , P. Korkolopoulou 2 , C. Piperi 1 , G. Levidou 2 ,
C. Adamopoulos 1 , A. Zizi-Sermpetzoglou 3 , N. Tsavaris 4 , E.K. Basdra 1 ,A.
G. Papavassiliou 1
1 Department of Biological Chemistry, University of Athens, School of Medicine,
Athens, GREECE, 2 First Department of Pathology, Laikon General Hospital,
University of Athens, School of Medicine, Athens, GREECE, 3 Department of
Pathology, Tzaneio General Hospital, Piraeus, GREECE, 4 Oncology Unit,
Department of Pathophysiology, Laikon General Hospital, University of Athens,
School of Medicine, Athens, GREECE
Background/purpose: Polycystins 1 and 2 (PC-1 and PC-2) constitute a family of
cellular proteins detected in a variety of epithelial cells throughout human tissues.
They function as mechanosensors and contribute to cellular homeostasis through
proliferation, differentiation and apoptotic processes. Nevertheless, their fundamental
role in cell-to-cell mechanical interactions, cell–matrix communication, tissue
morphogenesis and planar cell polarity connote their engagement in processes of
oncogenesis, including invasion and metastasis. The aim of the study was to
investigate the expression of PC-1 and PC-2 in colorectal cancer (CRC), identify
possible correlations with histopathological characteristics and explore the
underpinning signal transduction mechanisms.
Methods: The immunohistochemical expression of PC-1 and PC-2 was evaluated in
paraffin sections of 144 CRC patients and the results were statistically correlated with
clinical and pathologic parameters. Molecular mechanisms were explored by Western
blot, immunofluorescence and flow cytometry in SW480 CRC cell line expressing
PC-1 and PC-2.
ix92 | Abstracts Volume 23 | Supplement 9 | September 2012