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

676s Tumor Biology
10582 General Poster Session (Board #47G), Mon, 1:15 PM-5:15 PM
Antigens diagnoses in paraneoplastic neurological syndromes. Presenting
Author: Halina Rudnicka, Maria Sklodowska-Curie Memorial Cancer Center
and Institute of Oncology, Warsaw, Poland
Background: At present, paraneoplasmatic neurological syndroms (PNS)
are thought to be autoimmunological disorders. Neurological symptoms in
PNS result from the disturbance of the nervous system, with a participation
of the immune response triggered by the aberrant expression of the
so-called onconeuronal antigens of a tumour. Very important for PNS
diagnostics is the investigation of antineuronal antibodies (ANA) in the
serum. Different types of ANA are frequently associated with specific
tumors and with specific neurological syndromes.Investigations of serum
ANA in patients with breast cancer with the symptoms of PNS. Methods:
Investigations of ANA in serum were performed with the indirect immunofluorescence
test but the type of ANA was analyzed by the Western Blot
(WB) method . The presence of these antibodies which are included to the
group of “the so called well characterized” is believed to be a definite (95 –
100%) determinant of the PNS diagnosis. Results: We examined 147
patients with breast cancer suspected to have PNS, hospitalized at Breast
Cancer Clinic of the Institute of Oncology in Warsaw. The immunofluorescence
test was positive in 92 patients, however in 24 patients the WB
occurrence of “the well characterized” antibodies was found. In this group
we observed: in 4 patients the cerebellar degeneration (anti-Yo, anti-Ma2);
in 6 patients brainstem encephalitis and encephalomyelitis combined with
sensory neuropathy (anti-Ma2, anti-CV2, anti-Yo, anti-Hu, anti-Ri); 4
myastenic syndrome (anti-Hu,anti-Ri,anti-Ma2/Ta); 5 sensory neuropathy
(anti-Hu, anti-Yo, anti-Ma2, anti-Ri); and in single cases we also observed
polyneuropathy: Guillain-Barre (Ma2): Miller-Fisher syndrom (anti-Ma2/
Ta); cancer-associated retinopathy (anti-Yo); dermatomyositis (anti-Ri) and
scleroderma (anti-Yo). Conclusions: Our analysis indicates that the investigation
of the presence of ANA in the serum is the important in the diagnosis
of PNS in patients with breast cancer. The types of ANA correspond to the
individual paraneoplastic neurological syndromes which opens the proper
methods of treatment in PNS.
10584 General Poster Session (Board #48A), Mon, 1:15 PM-5:15 PM
Estimation of expected survival time using gene expression profiling for
tumor site origin. Presenting Author: William David Henner, Pathwork
Diagnostics, Redwood City, CA
Background: Expected survival is an important factor in treatment selection
and patient decision making. Gene expression profiling for tissue of origin
(GEP TOO) can be used to classify metastatic and poorly-differentiated
tumors according to the most likely primary site for difficult-to-diagnose
tumors. The Pathwork Tissue of Origin Test, (Redwood City, CA) generates
Similarity Scores (SS), one for each of the 15 tissues on the Tissue of Origin
Test Panel and sum to 100. The highest SS has been validated as the most
likely tissue of origin in a large validation study (Pillai et al. 2010). This
abstract reports the relationship between the highest SS for a sample and
patient survival. Methods: Two cohorts were analyzed in IRB-approved
studies. Cohort 1 consisted of 45 patients with carcinoma of unknown
primary treated empirically with therapy for carcinoma of unknown primary
with known outcome data including survival. Cohort 2 consisted of 107
patients receiving the TOO test in routine clinical practice and included in a
decision impact registry study. The relationship between the highest SS
generated by the TOO test was examined using parametric (Gamma) and
non-parametric (Cox Proportional Hazards) regression models with covariates
of age, gender and median survival of the cancer type indicated.
Logrank tests were performed to compare survival in patients with SS above
or below 50 in each cohort. Results: The highest SS generated by the TOO
Test was strongly and positively correlated with patient survival in both
Cohort 1 (p � 0.0093, Cox PH) and in Cohort 2 (p�0.0045, Gamma). In
Cohort 1, survival for patients with a SS � 50 was 5.9 mos and for patients
with a SS � 50 was 9.7 mos (p�0.03, logrank). In Cohort 2, survival for
patients with a SS � 50 was 10.6 mos and 22.6 mos for patients with a SS
� 50 (p�0.0073, logrank). Conclusions: The Similarity Scores generated
by GEP TOO Test have been validated as an aid to diagnosis for
difficult-to-diagnose malignancies. Two independent studies of this GEP
TOO Test demonstrated a strong positive relationship between the highest
SS and survival. This has the potential to expand the clinical utility of this
test beyond diagnosis to include prognosis. Further studies to examine this
question are underway.
10583 General Poster Session (Board #47H), Mon, 1:15 PM-5:15 PM
Antagonistic activity of acolbifene, fulvestrant, tamoxifen, and raloxifene
on cancer-associated genes in the mouse mammary gland. Presenting
Author: Ezequiel Calvo, Molecular Endocrinology, Oncology and Human
Genomics Research Center, Laval University and Laval University Hospital
Research Center, Quebec City, QC, Canada
Background: The efficacy and exceptionally good tolerance of estrogen
blockade in the treatment of breast cancer is well recognized. Acolbifene
(ACOL) is a novel and unique SERM completely free of estrogen-like
activity in both the mammary gland and uterus. To better understand the
specificity of ACOL, we have investigated its effect on the expression of a
set of genes modulated by estradiol (E2) in the mouse mammary gland.
Methods: ACOL, tamoxifen (TAM), raloxifene (RALOX) and fulvestrant
(FULV) were administered (0.01 mg/mouse; sc) to ovariectomized (OVX)
mice or to OVX mice simultaneously treated with E2 (0.05 �g/mouse; single
sc injection). Microarray screening followed by Q_RTPCR was used to
identify a reproducible set of E2 responsive genes. Results: From 128 genes
significantly modulated by E2, 108 genes were up-regulated and 20 were
down-regulated. Forty-nine of these genes were associated with tumorigenesis
while 22 are known to be associated with breast cancer. This set of 49
genes were used to determine the specificity of ACOL compared to another
pure antiestrogen in the mammary gland and uterus, namely FULV, as well
as to the mixed estrogen antagonists/agonists TAM and RALOX, in their
ability to block the effect of E2. Efficacy of reversal of the effect of E2 was
94%, 63%, 45% and 90% for ACOL, FULV, TAM and RALOX, respectively.
The overlap between all treatments was 30.6% (15/49). ACOL reversed the
effect of E2 on 42 of the 49 (85.7%) cancer-related genes. Between the
genes up-regulated by E2 and reversed by ACOL, seven are considered as
prognostic markers in breast cancer, namely Fgfr3, Fos12, Junb, Jdp2,
Gdf15, Greb1 and Tgm2. On the other hand, two genes down-regulated by
E2, namely Foxa1 and Fgfr2, were restored by ACOL. Conclusions: Taken
together, these data offer new information for a better understanding of the
previously demonstrated potent tumoricidal action of ACOL in human
breast cancer xenografts. The data also suggest, under the tested conditions,
superiority of ACOL over TAM and the other compounds to reverse the
effect of E2 on specific gene expression, thus supporting the interest of this
new 3rd generation SERM for the hormonal therapy and prevention of breast
cancer.
10585 General Poster Session (Board #48B), Mon, 1:15 PM-5:15 PM
Novel malignant-mesothelioma-associated antigens (Gene-X and THBS-2)
in the diagnosis of malignant pleural mesothelioma (MPM). Presenting
Author: Fumihiro Tanaka, University of Occupational and Environmental
Health, Kitakyusyu, Japan
Background: Malignant pleural mesothelioma (MPM) is a highly aggressive
malignant tumor of the pleura associated with asbestos exposure, and its
diagnosis is usually difficult at early stage. We identified novel mesothelioma-related
antigens, Gene-X and thrombospondin-2 (THBS-2), recognized
by tumor-infiltrating B cells (Cancer Sci 2009), but the clinical
significance in the diagnosis of MPM remains unclear. Methods: A total of
120 patients, who presented with a suspicion of MPM and received pleural
biopsy, were reviewed; 97 patients were finally diagnosed with MPM and
27 were with non-malignant diseases (NM). The antibody-titers against
Gene-X and THBS-2 in the sera were measured by ELISA method. Results:
The serum antibody-titer against THBS-2 was significantly higher in MPM
patients than in NM (P�0.01), but there was no difference in the serum
antibody-titer against Gene-X (Table). The receiver operating characteristic
(ROC) curve analysis showed a significant diagnostic value of serum
antibody-titer against THBS-2 with the area-under curve of 0.886 (95% CI,
0.797 - 0.975; P�0.001) in discrimination of MPM from NM diseases; the
sensitivity and specificity, when the cut-off value was 0.08, were 72.2%
and 95.5%, respectively. Conclusions: The serum antibody-titer against
THBS-2 can be a useful non-invasive marker in the diagnosis of MPM.
Antigens
MPM
(n�97)
Non-malignant
(n�23)
p value
(Mann-Whitney)
Gene-X
(mean) 0.49 0.48 p�0.997
(median) 0.39 0.36
THBS-2
(mean) 0.11 0.02 p�0.001
(median) 0.10 0.00
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