Annual Meeting Proceedings Part 1 - American Society of Clinical ...

666s Tumor Biology
10540 General Poster Session (Board #42E), Mon, 1:15 PM-5:15 PM
HER2 expression on circulating tumor cells (CTC) in patients with early
HER2-positive breast cancer: Results of the German SUCCESS B trial.
Presenting Author: Bernadette Anna Sophia Jaeger, Department of Gynecology
and Obstetrics, Ludwig-Maximilians-University, Munich, Germany
Background: Recent reports showed a discrepancy in the Her2-status of
metastases or minimal residual disease in blood and bone marrow compared
to the primary tumor in patients with breast cancer. The Her2-status
of CTC was prospectively evaluated in the German multicenter SUCCESS B
study. Methods: The SUCCESS B trial is a randomized Phase III study
comparing FEC-Docetaxel (Doc) vs. FEC-Docetaxel-Gemcitabine (Doc-G)
as well as Her2 targeted therapy with Trastuzumab as adjuvant treatment in
patients with early, Her2 positive, node positive or high risk node negative
primary breast cancer. As part of the translational research program, 23ml
of peripheral blood were drawn before adjuvant chemotherapy. In 638
samples CTC and Her2-status were assessed using the CellSearch System
(Veridex, USA). After immunomagnetic enrichment with an anti-Epcamantibody,
cells were labeled with anti-CK8/18/19, anti-CD45 antibodies as
well as a fluorescein conjugate antibody for Her2 phenotyping. Cutoff for
CTC-positivity was �1 CTC and for Her2 �1 CTC with strong Her2-staining
(���). Results: 40.2% of pts (n�257) were positive for CTC (mean 4.52;
range 0-1689). The number of detected CTC was distributed as follows: 1
CTC (n�112; 43.6%), 2 CTC (n�65; 25.3%), 3 CTC (n�36; 14.0%), 4
CTC (n�12; 4.7%) and �5 CTC (n�31; 12.1%). Her2 status on CTC was
negative or weak in 12.5% (n�32) and 8.9% (n�23) of CTC positive
patients respectively and therefore categorized as Her2 negative. In 21.4%
(n�55) we detected moderate and in 57.2% (n�147) strong Her2staining
of �1 CTC per sample. Therefore 57.2% of CTC-positive samples
were diagnosed as Her2 positive and 21.4% as questionable. No association
was found between the detection of CTC or the Her2-status on CTC
with tumor size, histopathological grading, hormone receptor status or
axillary lymph node involvement. Conclusions: The data of this trial
confirms the frequent discordance of Her2 expression on CTC compared to
the primary tumor. Survival data within the Success B trial will give further
insight into the tumor biology of Her2 positive disease and the role of the
Her2-status on CTC to predict treatment efficacy.
10542 General Poster Session (Board #42G), Mon, 1:15 PM-5:15 PM
Serum hepatocyte growth factor and interleukin-6 as prognostic markers
for stage III non-small cell lung cancer. Presenting Author: Hideki Ujiie,
Department of Thoracic Surgery, Saitama Cancer Center, Saitama, Japan
Background: We surveyed prognostic biomarkers for resectable non-small
cell lung cancer (NSCLC). Methods: We obtained preoperative serum from
109 patients admitted to our facility, and measured the levels of hepatocyte
growth factor (HGF), interleukin-6 (IL-6), and nicotinamide
N–methytransferase (NNMT) in the sera by the ELISA method. We also
examined the clinical backgrounds of the patients. Results: The median
HGF and IL-6 contents in sera from 109 patients were 860 pg/ml and 2.7
pg/ml, respectively. Analysis of survival curves indicated that HGF or IL-6
levels higher than the median were associated with poor overall survival
(HGF, P � 0.019; IL-6, P � 0.002). On the other hand, carcinoembryonic
antigen (CEA), a known tumor marker, and NNMT, which we found to be a
candidate tumor marker, exhibited no correlation with the prognosis. The
tumor status (pT factor) and stage were strong prognostic indicators (P �
0.001). In addition, we analyzed stage III lung cancer alone. Higher HGF or
IL-6 levels were associated with poor overall survival (HGF, P � 0.016;
IL-6, P � 0.013). Disease-free survival was also affected by these cytokine
contents, but not statistically significantly. The prognosis of patients with
adenocarcinomas (ADC) was better than that of patients with other
histological types. However, the pT factor and nodal status (pN factor) were
not associated with the survival of stage III patients. Conclusions: The levels
of HGF and IL-6 in serum could be useful prognostic indicator of the
survival of stage III NSCLC patients undergoing surgery and chemotherapy.
10541 General Poster Session (Board #42F), Mon, 1:15 PM-5:15 PM
Detection and HER2 expression of circulating tumor cells in advanced
gastric cancer patients. Presenting Author: Satoshi Matsusaka, Department
of Gastroenterology, Gastroenterology Center, Cancer Institute Hospital;
Clinical Chemotherapy, Cancer Chemotherapy Center, Japanese
Foundation for Cancer Research, Tokyo, Japan
Background: This study was aimed at detecting and HER2-expressiong
circulating tumor cells (CTC) in peripheral blood of chemo-naïve or
chemo-resistant patients with advanced gastric cancer. Methods: All
patients were enrolled using institutional review board-approved protocols
at the Cancer Institute Hospital in the Japanese Foundation for Cancer
Research and provided informed consent. The study population consisted
of patients of age 18 years or older with histologically proven advanced
gastric cancer. A total of 140 patients with advanced gastric cancer were
enrolled into a prospective study. We used CellSearch system for detection
and HER2 expression for CTC. Results: We detected �1 CTC/7.5ml in 80 of
140 patients (57.1%). HER2-positive CTC were observed in 19 of 80
CTC-positive patients (23.8%), including 6 patients with HSR2-negative
primary tumors. 21 patients with HER2-positive primary tumors administered
trastuzumab in combination with chemotherapy (Xeloda�cisplatin;
15, weekly Paclitaxel; 5). We detected �1 CTC/7.5ml at the baseline in 11
of 20 patients with trastuzumab treatment. HER2-positive CTCs were
observed in 6 of 11 CTC-positive patients (54.5%). Patients with HER2positive
CTC at the baseline were shorter PFS than those with HER2negative
CTC at the baseline. Conclusions: HER2 expression on CTC was
associated with chemo-resistance. Information on the HER2 status of CTC
might be helpful for stratification of HER2-directed therapies.
10543 General Poster Session (Board #42H), Mon, 1:15 PM-5:15 PM
Promoter methylation of MGMT in paired primary and recurrent glioblastomas.
Presenting Author: Li Bie, The First Hospital of Jilin Universtiy,
Changchun, China
Background: Epigenetic sliencing of MGMT gene promoter in primary
glioblastomas (GBM) of pts subsequently treated with temozolomide (TMZ)
is associated with prolonged survival. Further, several studies have observed
a change in MGMT silencing in paired primary and recurrent GBM.
However, the relationship between this “MGMT switch” and patients
outcome is largely unknown. Methods: The study involved primary and
recurrent tumor tissue samples from 53 GBM pts diagnosed and treated
within the First Hospital of Jilin University from Jan 2003 to Nov 2010.
After surgical treatment, all pts were subjected to radiotherapy with
concomitant administration of TMZ (75 mg/m2 /d), followed by 5 cycles of
adjuvant TMZ given at 4-weeks intervals. Pts that experienced recurrent
tumors received TMZ at a dose of 200 mg/m2 /5 days for 4 weeks. 53 pts
underwent 58 further operations after recurrence (5 pts received a third
surgery). MGMT promoter methylation levels were determined using qMSP.
The relationship between “MGMT switch” and clinical outcome was
investigated. Results: Fifty three (M/F�33/20; median age: 49.2�3.6,
range: 19.5-72.3 ys) underwent a first operation for GBM. qMSP analysis
revealed MGMT promoter methylation in 19 pts (35.8%, group A, OS 31.5
ms); no methylation in 34 pts (64.2%, group B, OS 7.9 ms). In the
recurrent tumors, MGMT promoter methylation was detected in 25 pts
(47.2%); and no methylation in 28 pts (52.8%). Comparison of individual
pairs of primary and recurrent GBMs revealed a changed methylation status
in 10 (18.9%), including eight changed from unmethylated to methylated
tumors (15.1%, group C, OS 29.4 ms), two changed from methylated to
unmethylated tumors (3.8%, group D, OS 10.5 ms). Median overall
survival was 12.1 ms. MGMT promoter methylation was significantly
associated with a favorable clinical outcome (group A vs group B,
p�0.0027). The outcome of pts were not significant different between A
and C (p�0.01). Conclusions: The methylation status of the MGMT
promoter was altered in 10 (18.9%) of 53 recurrent GBM after chemoradiotherapy.
Eight pts changed from unmethylated to methylated who have a
median overall survival similar to methylated pts. The pts changed from
methylated to unmethylated who have poor outcome.
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