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patients harboring a T/T genotype than for patients with the C/C or C/T genotypes
(p= 0.01). In the case of the c3158A > C polymorphism, patients harboring a C/C
genotype had a lower OS than patients with an A/A or A/C genotypes (p = 0.047).
Conclusions: In this study, we identified common germline variants in LRIG1 gene
predicting clinical outcome in patients with mCRC receiving first-line
oxaliplatin-based chemotherapy.
Disclosure: All authors have declared no conflicts of interest.
545P MMP-9 AND VEGFR EXPRESSION HAS PROGNOSTIC
SIGNIFICANCE AFTER RESECTION FOR PRIMARY TUMOR
AND METASTATIC SITE IN COLORECTAL CANCER
M.A. Lee 1 , S.T. Oh 2 , W.K. Kang 2 , S.W. Kim 3
1 Medical Oncology, Seoul St. Mary’s Hospital, of the Catholic University, Seoul,
KOREA, 2 Surgery, Seoul St. Mary’s Hospital, Seoul, KOREA, 3 Gastroenterology,
Seoul St. Mary’s Hospital, Seoul, KOREA
Background: Resection for metastatic lesion has been commonly done in stage
colorectal cancer, showing better survival outcome than other GI malignancy.
Although R0 resection in primary and metastatic lesion is done in stage IV cancer,
recurrence should be developed and cure is rare. In the present study, we reviewed
and analyzed the protein expression and the recurrence to determine the prognostic
factor in stage IV colorectal cancer.
Method: Tissue specimens from 130 patients with metastatic colorectal cancer were
analyzed. All patients were diagnosed as metastatic colorectal cancer between Jan,
2000 and Aug, 2008 at Seoul St. Mary’s hospital, the Catholic University. We
performed immunohistochemical staining using tissue microarray for Wnt 3a, Wnt
5a, VEGFR, and MMP-9. We analyzed the clinicopathological characteristics through
the medical record and the association with protein expressions.
Result: Of the 130 patients, Male was 78 (60%), and female was 52 (40%).
Median age was 59.5 years old (range: 27-81). Colon cancer was 76 (58.5%) and
rectal cancer was 54 (41.5%). 94 patients were initially diagnosed as stage IV,
but took curative resection for primary lesion and metastasectomy. The other 36
patients had recurrent disease as distant metastasis after curative surgery, and
then took metastasectomy. The Wnt 5 expression showed the tendency of
positive perineural invasion (p = 0.065), but there was no correlation between
protein expression and other pathological factors. As a prognostic factor for
recurrence, Negative MMP expression showed significantly longer time t o
recurrence (TTR) than positive group (13mon vs, 10 months, p = 0.010) and
VEGFR expression showed a correlation with TTR (15.7 mon for negative vs.
11.1 mon for positive, p = 0.060). There was no correlation between recurrence
and pathological findings such as lymphatic, vascular or perineural invasion, and
other protein expressions.
Conclusion: VEGFR and MMP-9 expression showed prognostic significance for
recurrence in stage IV or recurrent colorectal cancer after metastasectomy. Unlikely
the stage III colorectal cancer, pathological findings such as lymphovascular or
perineural invasion did not have association with recurrence.
Disclosure: All authors have declared no conflicts of interest.
546P NEUROPILIN-1 (NRP1) EXPESSION IN TUMOR METASTASIS
OF PRIMARY AND COLORECTAL CANCER: IMPLICATIONS
FOR ANTIANGIOGENIC THERAPY
M.J. Ortiz-Morales1 , C. Morales2 , A. Gómez3 , G. Pulido4 , M.T. Cano Osuna5 ,
J. Jiménez6 , P. Sánchez6 , M. Medina7 , J. De La Haba Rodriguez8 ,E.
Aranda Aguilar8 1
Medical Oncology, Hospital Universitario Reina Sofía, Córdoba, SPAIN,
2
Medicine University, Department of Cell Biology, Physiology and Immunology,
Córdoba, SPAIN, 3 Medical Oncology, Hospital Reina Sofía, Córdoba, SPAIN,
4
Medical Oncology, Universitary Hospital Reina Sofía, Córdoba, SPAIN,
5
Oncologia Medica, Hospital Universitario Reina Sofia, Cordoba, SPAIN,
6
Medical Oncology, Universitay Hospital Reina Sofia, Córdoba, SPAIN,
7
Pathological Anatomy, Universitary Hospital Reina Sofía, Córdoba, SPAIN,
8
Medical Oncology, Reina Sofía Hospital. Biomedical Research Institute (IMIBIC),
Cordoba, SPAIN
Introduction and objective: Vascular development is critical in tumor biology and
targeted therapies against angiogenesis process have proven their therapeutic efficacy.
Neuropilin-1 (NPR1), a membrane glycoprotein that works as a receptor for
semaphorins, is also a co-receptor for VEGF-A165 and it is expressed in endothelial
cells and in many other tumors. Very few studies about this protein in primary and
secondary tumors have been reported with contradictory conclusions 1,2 . The aim of
this study is to analyze the relationship between the expression of NRP1 in colorectal
cancer patients in primary tumor and metastases and clinical and pathologic features,
treatment response, progression-free interval and overall survival.
Patients and methods: From 1995 to 2010, 70 patients with available biological
material in paraffin of primary tumor and metastases (liver and/or lung) have been
selected. NRP1 expression was performed using immunohistochemistry with
Annals of Oncology
neuropilin-1 Rabbit Monoclonal Antibody Catalog # 2621-1 (ATOM) at 1:75
dilution. Vascular endothelium was used as positive control and tumor sample
without antibody as negative control. Clinical and pathological data of patients,
treatments administered, toxicity, response, progression-free interval and overall
survival were registered.
Results: The mean age of patients was 63 years. 51 patients (85%) were
adenocarcinoma and 46 patients (76%) were moderately differentiated. 34 patients
(56.7%) presented metastatic disease at the moment of primary tumor diagnosis.
NRP1 expression exists in 100% (120) of samples analyzed.
Conclusions: In our study, in contrast to latest published data 2 , no differences about
intensity and frequency of expression of NRP1 were found between primary and
metastatic samples. It is not possible to establish any relationship between tumor
response to treatment and evolution. References: 1. Parikh AA, Fan F, Liu WB, et al.
Neuropilin-1 in human colon cancer: expression, regulation, and role in induction of
angiogenesis. Am J Pathol 2004;164:2139-51. 2. Jubb AM, Strickland LA, Liu SD,
Mak J, Schmidt M, Koeppen H. Neuropilin-1 expression in cancer and development.
J Pathol 2012;226:50-60.
Disclosure: All authors have declared no conflicts of interest.
547P PROGNOSTIC SIGNIFICANCE OF COMBINED POSITIVITY OF
LYMPHATIC, VASCULAR, AND PERINEURAL INVASION
(TRIPLE POSITIVE) IN STAGE II/III COLORECTAL CANCER; A
NEW PARADIGM WORTH TO INVESTIGATE?
F. Dane 1 , M.A. Ozturk 1 , M. Koçar 1 , B.M. Atasoy 2 , B. Aktas 1 , F. Telli 1 ,
M. Kanıtez 1 , M. Bes¸irog˘ lu 1 , P.F. Yumuk 1 , S.N. Turhal 1
1 Internal Medicine Dpt., Medical Oncology Div., Marmara University Faculty of
Medicine, Istanbul, TURKEY, 2 Radiation Oncology Dpt., Marmara University
Faculty of Medicine, Istanbul, TURKEY
Background: Despite the studies showing the impact of each lymphatic, vascular or
perineural invasion on prognosis separately, the exact effect of these parameters in
together (triple positive) on prognosis is not known. In this study, we assessed the
pathological features and the survival outcomes of triple positive colorectal cancer
patients.
Methods: The files of stage II/III colorectal cancer (CRC) patients (n = 532) who
received adjuvant systemic treatment following curative resection in our center were
analyzed, retrospectively. Tumors with vascular, lymphatic, and perineural invasions
were called triple positive (TP), all others were called non-triple positive (NTP)
tumors. Patients with unknown vascular, lymphatic or perineural invasion status (n
= 93) were excluded from the analysis. Adjuvant therapy was consisted of either
fluorouracil or oxaliplatin-based chemotherapy (CT) regimens. Rectal cancer patients
were given adjuvant radiation therapy also. Survival was determined using the
Kaplan-Meier method, with differences determined by multivariate analysis using the
Cox multiple hazards model. Results were compared using the log-rank test.
Results: A total of 439 patients (243 male: 196 female) with stage II/III colorecral
cancer who received adjuvant therapy were evaluated retrospectively. The median age
was 60 (range: 23–84 years). Median follow-up was 36 months. Fifteen percent of the
patients were TP. The rate of TP tumors were 4%, 13,6%, and 29% in T2, T3, and T4
tumors, respectively (p:0.001). The rate of TP tumors were 5,6%, 13,9%, and 40,5%
in N0, N1, and N2 tumors, respectively (p:0.0001). There were no relation between
TP tumors rates and age, gender or tumor localization (p > 0.05). Five years DFS and
OS rates were 37,7% vs 64,7% (p:0.0001) and 53,4% vs 78,1% (p:0.0001) for TP and
NTP tumors, respectively.
Conclusion: Our findings revealed that patients with TP tumors have inferior
survival outcomes when compared to NTP tumors. However results of multivariate
analyses for DFS and cancer specific OS did not support the preanalysis hypothesis
of TP being a poor prognostic sign in early stage CRC patients. Nevertheless, we
believe that accurate answer to this question can be given via retrospective analysis of
prospectively collected data from multi-center clinical trials.
Disclosure: All authors have declared no conflicts of interest.
548P MUTATION OF EITHER RAS OR BRAF CORRELATES WITH
MGMT METHYLATION AND MUTATION OF PIK WITH PTEN
METHYLATION, BUT NONE OF THESE IS ASSOCIATED WITH
STAGE IN COLORECTAL CANCER
B. Metzger1 , M.A. Dicato2 , G. Mahon3 , S. Obertin3 , J. Kayser3 1
Laboratory, Foundation for Research on Cancer, Luxembourg, LUXEMBOURG,
2
Hematology-Oncology, Hospital Centre of Luxembourg, LUXEMBOURG,
3
Foundation for Research On Cancer, Hospital Centre of Luxembourg,
LUXEMBOURG
Background: In a previous study of 222 patients we showed how epigenetic and
genetic changes during oncogenic progression could possibly explain the adenomacarcinoma
sequence: first, methylation of promoters of H-cadherin gene followed by
MGMT methylation, K-ras oncogene G to A point mutations, activation of B-raf
gene by a V600E mutation finally methylation of E-cadherin. (ASCO 2011,
ix186 | Abstracts Volume 23 | Supplement 9 | September 2012