Mucinous ovarian cancer is distinct from extra-ovarian ...
Transcript of Mucinous ovarian cancer is distinct from extra-ovarian ...
Mucinous ovarian cancer is distinct from extra-ovarian metastases and evolves from benign and borderline precursors.
Kylie L Gorringe
Group Leader (Junior Faculty)
Peter MacCallum Cancer Centre
Faculty Disclosure
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March 30 - April 2, 2014
Sheraton Sonoma County
Petaluma, California
Off-Label Product Use
Will you be presenting or referencing off-label or investigational use of a therapeutic product?
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Where does MOC come from?Benign
Borderline
Extra-ovarian metastases
Low grade MOC
High grade MOC
Comparison with other tumour typesEvent
COAD ColonAdenocarcinoma 129
DSTAD DiffuseTypeStomachAdenocarcinoma 70
ECAD EndocervicalAdenocarcinoma 26
IHCH IntrahepaticCholangiocarcinoma 29
IPMN IntraductalPapillaryMucinousNeoplasm 8
MACR MucinousAdenocarcinomaColon/Rectum 23
MCN MucinousCysticNeoplasm 8
MSTAD MucinousStomachAdenocarcinoma 20
PAAD PancreaticAdenocarcinoma 258
PANET PancreaticNeuroendocrineTumor 98
PSC SerousCystadenomaofthePancreas 8
PSTAD PapillaryStomachAdenocarcinoma 6
READ RectalAdenocarcinoma 68
SOC SerousOvarianCancer 311
SPN PancreaticSolidPseudopapillaryNeoplasm 8
SSRCC StomachSignetRingCellCarcinoma 9
STAD StomachAdenocarcinoma 227
TSTAD TubularStomachAdenocarcinoma 61
UEC UterineEndometrioidCarcinoma 195
USC UterineSerousCarcinoma 43
APP Appendicealneoplasms 10-38*
BEN Benignmucinouscystadenoma 4-22*
BDL Borderlinemucinoustumour 30-44*
MOC Mucinousovariancarcinoma 195
Where does MOC come from?
BenignBorderline
Extra-ovarian metastases
Low grade MOC
High grade MOC
xWith expert pathology
Copy number burden crucial for progressionF
raction g
enom
e a
ltere
d b
y C
N
A
B C
Benign
Borderline
G1 MOC
G2 MOC
G3 MOC
Gain Loss
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 202122 X
BE
N
BD
L
G1
G2
G3
EO
M
EOM
G3
G2
G1
BDL
BEN
●●●
●
●
●
●
●
0.0
0.2
0.4
0.6
BEN BDL 1 2 3 EOM
Grade
FG
A
0 0.05 0.1 0.15 0.2
ValueP-value
Figure 2. CN analysis. A. Comparison of CN frequency across the genome, compar-
ing benign (BEN), borderline (BDL), MOC grade 1 (G1), grade 2 (G2) and grade 3
(G3) . B. Fraction of the genome altered (FGA) by group including extra-ovarian
(EOM) mucinous tumours (p<0.001). Tukey post-test comparison p-values shown at
right.C. Disease-specific survival by FGA. Score (logrank) test = 11.98 on 1 df,
p=0.002.
Dis
ease-s
pecific
surv
ival
BEN BDL G1 G2 G3
10%
Multivariate cox regression: p=0.011,
HR = 4.4, 95% CI 1.4-14(with stage, grade, ERBB2 amplification and 9p CN
loss; selected by AIC)
logrank P=4x10-5
Where does MOC come from?
BenignBorderline
Extra-ovarian metastases
Low grade MOC
High grade MOC
xWith expert pathology
Cell of origin??
AcknowledgementsCampbell/Gorringe Labs Pathology GAMuT - Australia
Ian Campbell Stephen Fox Westmead (NSW)
Dane Cheasley Prue Allan Anna deFazio
Simone Rowley Catherine Kennedy
Mei-Sim Lung GAMuT - Victoria Garvan (NSW)
Na Li WEHI Goli Samimi
Tanjina Kader Clare Scott Maret Boehm
Sakshi Mahale Matt Wakefield QIMR (QLD)
Hugo Saunders RMH/RWH Georgia Chenevix-Trench
Lisa Devereux Sumi Ananda
Georgina Bing Jan Pyman GAMuT - International
Abhimanyu Nigam Michael Christie Edinburgh (UK)
Carolina Salazar Alison Hadley Charlie Gourley
Former Orla McNally Michael Churchman
Sally Hunter Hudson Institute/Southern BCCA (Canada)
Georgie Ryland Andrew Stephens David Huntsman
David Choong Yoland Antill Jessica McAlpine
Michelle Torres Tom Jobling Blake Gilks
AOCS/CASCADE University of Calgary (Canada)
Bioinformatics David Bowtell Martin Koebel
Jason Li Nadia Traficante Mayo Clinic (US) Scott Kaufmann
Richard Lupat Sian Fereday Scott Kaufmann
Kaushalya Amarasinghe Joy Hendley COEUR tissue bank (Canada)
Niko Thio Kathryn Alsop
Magnus Zethoven Leanne Bowes
Genomics Core
Gisela Mir-Arnau
Gain
Loss
Chromosome
BEN (22)
BDL (39)
G1 (87)
G2 (81)
G3 (24)
A
B C
Benign
Borderline
G1 MOC
G2 MOC
G3 MOC
Gain Loss
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 202122 X
BE
N
BD
L
G1
G2
G3
EO
M
EOM
G3
G2
G1
BDL
BEN
●●●
●
●
●
●
●
0.0
0.2
0.4
0.6
BEN BDL 1 2 3 EOM
Grade
FG
A
0 0.05 0.1 0.15 0.2
ValueP-value
Figure 2. CN analysis. A. Comparison of CN frequency across the genome, compar-
ing benign (BEN), borderline (BDL), MOC grade 1 (G1), grade 2 (G2) and grade 3
(G3) . B. Fraction of the genome altered (FGA) by group including extra-ovarian
(EOM) mucinous tumours (p<0.001). Tukey post-test comparison p-values shown at
right.C. Disease-specific survival by FGA. Score (logrank) test = 11.98 on 1 df,
p=0.002.
Progression from borderline to grade 3 metastatic
P=2x10-9 P=8x10-7