The Clinical significance of DNA ploidy as a prognostic factor in

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The Clinical significance of DNA ploidy
as a prognostic factor in patients with
Borderline Ovarian Tumor
Retrospective study
Ji Young Lee, MD, PhD, David Marchetti, MD, M Steven Piver, MD
Department of Obstetrics and Gynecology
Sisters of Charity Hospital, Buffalo, NY
INTRODUCTION
Howard Taylor
Described Borderline Ovarian Tumor as
“semi-malignant”
….propensity to metastasize but maintained
a rather indolent course…
Surg Gynecol Obstet 1929; 48: 204-230
10-20% of epithelial ovarian tumor
Mean age 45.7 yr
75% of tumors are Stage I
5 YSR for early stage tumors ≥ 95%
Recurrence rate 8~32%
Risk factors for recurrence
FIGO stage, Age, Residual disease, Histology,
DNA ploidy etc.
DNA Ploidy
The most important prognostic factor
in 370 patients with the borderline ovarian tumor
Int J Gynecol Oncol 1993 3: 349
A Review of the Literature
OBJECTIVES
1. Report the results regarding DNA ploidy and other
Clinicopathologic variables
2. Evaluate the clinical significance of DNA Ploidy
in 30 consecutive patients with Borderline Ovarian
Tumor
MATERIALS & METHODS
Retrospective Study
Review of Cancer Registry of Sisters Hospital
A total of 30 consecutive patients with
Borderline Ovarian Tumor
Histologic evaluation of Paraffin Tissue Blocks
DNA Flow Cytometry for DNA ploidy Analysis
-Primary Tumor
Histology
Definition Malignant characteristics of epithelial hyperplasia
or stratification, mitotic activity, and cellular/nuclear atypia
No Stromal Invasion
MUCINOUS TYPE
DNA Flow Cytometry
by USLABS (Irvine, CA)
Diploid ( DI=1.0, single peak)
Aneuploid (DI;1.1-1.9), Multi-peak
RESULTS
….and DISCUSSION
Patients (No.)
Age Distribution
of Borderline Ovarian Tumor
8
MEAN AGE 54.5 yo
7
6
5
4
3
2
1
0
20-29
30-39
40-49
50-59
60-69
70-79
80-89
Age
Age distribution of Borderline Ovarian Tumor
Sep 1993 – Sep 2004 in Sweden
Int J Gynecol Cancer 2008;18:453–459.
Patients (No.)
Histology and Age Distribution
of Borderline Ovarian Tumor
5
4
Serous
3
Mucinous
2
Mixed
1
0
20-29
30-39
40-49
50-59
60-69
70-79
80-89
Age
Patients (No.)
DNA Ploidy and Age at Diagnosis
6
Diploid
5
4
Aneuploid
3
2
1
0
20-29
30-39
40-49
50-59
60-69
70-79
80-89
Age
The relationship of Histopathology
and FIGO stage of disease
Serous
Mucinous
Mixed
Total
IA
8(50%)
4(50%)
2
14
IB
1(8%)
1
1
3
Stage (%)
IC
4(21%)
0
0
4
Total
II
0
1
1
2
III
3(21%)
1
0
4
NA
0
1
2
3
16
8
6
30
The relationship of DNA ploidy and
Histology of disease
DNA ploid
Aneuploidy
Diploidy
Histology
Serous Mucinous Mixed
4 (45%) 2 (22%) 3 (33%)
12 (58%) 6 (28%) 3 (14%)
Total
9 (100%)
21 (100%)
Patients (No.)
DNA ploidy and Histologic type
14
12
58%
10
8
28%
6
14%
4
2
0
Serous-Diploid
Serous-Aneuploid Mucinous-Diploid
MucinousAneuploid
Mixed-Diploid
Mixed-Aneuploid
Histology-DNA Ploidy
The relationship of DNA ploidy and
FIGO stage of disease
DNA ploid
Aneuploidy
Diploidy
FIGO Stage
IA
IB
IC
II
III
Unstaged
Total
2
1
2
1
2
1
9 (30%)
12
2
2
1
2
2
21 (70%)
pl
oi
d
lo
id
-D
ip
-A
ne
up
lo
Un
id
sta
ge
dDi
Un
pl
sta
oi
d
ge
dAn
eu
pl
oi
d
III
III
lo
id
IIAn
eu
p
IIDi
IC
-A
ne
up
lo
id
lo
id
-D
ip
IC
IB
-A
ne
up
lo
id
lo
id
IB
-D
ip
lo
id
IA
-A
ne
up
IA
-D
ip
lo
id
Patients (No.)
DNA Ploidy and Disease Stage
14
12
Diploid
10
8
Aneuploid
6
4
2
0
Stage-DNA Ploidy
Characteristics of 30 patients
Characteristics
Age
< 50
≥ 50
Ethnicity
Caucasian
African-American
FIGO Stage
IA
IB
IC
II-III
Unstaged
Pelvic Cytology
positive
Negative
Histology
Serous
Mucinous
Mixed
Chemotherapy
Yes
No
TOTAL
(n=30)
Diploid
(n=21)
Aneuploid
(n=9)
p value
11
19
5
16
6
3
0.09
29
1
21
8
1
0.002
14
3
4
6
3
12
2
2
3
2
2
1
2
3
1
0.007
6
24
4
17
2
7
0.1
16
8
6
12
6
3
4
2
3
0.4
4
26
3
18
1
8
Histology
Borderline Ovarian Tumor
Tropé CG. Seminars in surgical oncology 2000 9(1)69 –75
The relation of histopathology
to ploidy status
Histopathology
Serous
Mucinous
Endometrioid
Clear cell
Mixed
Total
Number
of cases (%)
219 (54.9)
171 (42.9)
5 (1.2)
1 (0.2)
3 (0.8)
399
Diploid Aneuploid
No FCM
167
127
3
—
2
27
32
2
1
1
25
12
—
—
—
299
63
37
Int J Gynecol Cancer 2008;18:453–459.
Overall Recurrence and survival
in Borderline ovarian tumor
Stage I
Stage II & III
Total
N
686
219
905
Recurred
29
40
69(7.6%)
Died
9
22
31(3.4%)
Rubin SC, Sutton GP
(2001,Ovarian cancer 2nd edition)
DNA Ploidy and Prognosis
in Borderline Ovarian Tumor (I)
Cancer 1992 69(10): 2510
DNA Ploidy and Prognosis
in Borderline Ovarian Tumor (II)
Seidman JD et al. Cancer 1993;71:12
…DNA ploidy may be of little prognostic
importance
Harlow BL et al. Gynecol Oncol 1993;50:305
…No correlation between DNA ploidy
and Survival or Recurrence
Mean Follow-up 36 months ( range 6-72 months )
No recurrence in 30 patients
No death from disease
Chemotherapy was given to 4 of 30 patients
(1 stage IIC-Aneuploidy and 3 IIIC stage-Diploidy)
CONCLUSION
DNA was not recognized as an important
prognostic factor in this study
 More prolonged follow-up will be needed to
evaluate the clinical correlation between
DNA ploidy and recurrence / survival
 Reassess the quality and quantity of tissue blocks
for DNA Ploidy analysis

REFERENCES
1. Ta ylor HC. Mali gnant and semim ali gnant tu mors of the ovary. Surg Gynecol Obstet
1929;48:204 -30.
2. Zanetta G, Rota S, Chiari S, Bonazzi C, Bratina G, and Mangioni C. Behavior of
borderli ne tumors with particular interest to persisitence, recurre nce, and progression to
invasive carcinoma: Prospective study. J Cli n Oncol 2001;19:2658 -64.
3. McKenney J, Balzer BL, Longacre TA. Patte rnsof stromal invasion in ovarian serous
tumors of low mali gnant potential (borderli ne tumors): A reevaluation of the concept of
stromal mi croinvasion. Am J Surg Pathol 2006;30:1209-21.
4. Kurman RI, Trim ble CL. The behavior of serous tumors of low mali gnant potential;
Are they ever mali gnant? Int J Gynecol Pathol 1993;12:120 -7.
5. Creasman WT, Park R, Norris H, et al. Stage I : B orderli ne oarian tumors. Obstet
Gynecol 1982;59:93 -6.
6. Sil va EG, Gershenson DM, Malpica A, Deavers M. The recurrence and the overall
survival rates of ovarian serous borderline neoplasms with n oninvasive im plants is time
dependent. Am J Surg Pathol 2006;30:136 7-71.
7. Dresc her CW, Fli nt A, Hpkins MP, Roberts JA. Prognostic signifi cance of DNA
content and nuclear morphology in borderline ovarian tumors. Gynecol Oncol
1993;48:242 -6.
8. Chambers JT, Merino MJ, Kohorn EL, Schwartz PE. Borderli ne ovarian tumors. Am J
Obstet Gynecol 1988;159:1088 -94.
9. Bostwick DG, Taze laar HD, Ball on SC, Hendrickson MR, Kempson RL. Ovarian
epitheli al tumors of b orderli ne mali gnancy. A cli nical and pathologic study of 109 cases.
Cancer 1986;58:2052 -65.
10. Lai CH, Hsue h S, Chang CJ, Tse ng CJ, Hua ng KG, Chou HH, et al. The role of DNA
fl ow cytomery in borderli ne mali gnant ovarian tumors. Cancer 1996;78:79 4-802.
11. Friedlander ML, Russe ll P, Taylor IW, Hedley DW, Tattersall MHN. Flow
cytometric analy sis of cell ular DNA content as an adjunct to the diagnosis of ovarian
tumors of borderli ne mali gnancy. Pathology 1984;16:301 -6.
12. Fu YS, Ro J, Reaga n JW, Hall TL, Berek J. Nuclear deoxyribonucleic acid
heterogeneity of ovarian borderli ne mali gnant serous tumors. Obstet Gynecol 1986;67:
478-82.
13. Dietel M, Arps H, Rohlff A, Bodecker R, Niendorf A. Nuclear DNA content o f
borderli ne tumors of the ovary: correlation with hi stology and signifi cance for prognosis.
Virchows Arch A Pathol An at Histopathol 1986;409: 829 -36.
14. Kaern J, Trope CG, Kristensen GB, Abeler VM, Pettersen EO. DNA ploidy the most
im portant prognostic factor in patients with borderli ne tumors of the ovary. Int J Gynecol
Cancer 1993;3:349 -58.
15. Padberg BC, Arps H, Franke U, Thiedemann C, Rephenning W, Stegner HE, et al.
DNA cytophoto metry and prognosis in ovarian tumors of borderli ne mali gnancy. Cancer
1992;69:2510 -4.
16. Seidman JD, Norris HJ, Griffi n JL, Hitchcock CL. DNA fl ow cytometric analy sis of
serous ovarian tumors of low mali gnant potential. Cancer 1993;71:3947 -51.
17. Demi rel D, Laucirica R, Fishman A, Owens RG, Grey MM, Kaplan AL, et al.
Ovarian tumors of low mali gnant potential. Correlation of DNA index and S-phase
fraction with histopathologic grade and cli nical outcome. Cancer 1996;77:1494 -500.
18. de Nictoli s M, Montironi R, Tomm asoni S, Carinelli S, Ojeda B, Matias-Guiu X, et
al. Serous borderli ne tumors of the ovary. A cli nicopathologic, imm unohistochemi cal,
and quantitative study of 44 cases. Cancer 1992;70:152 -60.
19. Harlow BL, Fuhr JE, McDonald TW, Schwartz SM, Beuer lein FJ, Weiss NS. Flow
cytometry as a prognostic indicator in women with borderli ne epitheli al ovarian tumors.
Gynecol Oncol 1993;50:305 -9.
20. Ingelm an-Sundberg A. Classifi cation and stagin g of mali gnant tumors in the female
pelvis. Acta Obstet Gynecol Scand 1971;50:1-7.
21. Hedley DW, Freidlander ML, Taylor IW, et al. Method for analy sis of cell ular DNA
content o f paraffi n-embedded pathological material using fl ow cytometry. J Histochem
Cytochem 1983;31:1333.
22. Heintz AP, Odicino F, Maisonneuve P, Bell er U, Benedet JL, Creasman WT, et al.
Carcinoma of the ovary. Int G Gynecol Obstet 2003;83:135 -66.
23. Sherman ME, Mink PJ, Curtis R, Cote TR, Brooks S, Hartge P, et al. Survival among
women with b orderli ne ovarian tumors and ovarian carcinoma: a population-based
analy sis. Cancer 2004;100:1045 -54.
24. Trim ble CL, Kosary C, Tr im ble EL. Long-term survival and patte rns of care in
women with ovarian tumors of l ow mali gnant pote ntial. Gynecol Oncol 2002;86:34 -7.
25. Kaern J, Trope C, Kjorstad KE, beler V, Pettersen EO. Cell ular DNA content as a
new prognostic too l in patients with borderli ne tumors of the ovary. Gynecol Oncol 1990;
ACKNOWLEDGEMENT
M Steven Piver, MD
David Marchetti, MD
Judine Davis, MD
Anthony Pivarunas, DO
Pathology Department
USLABS, CA
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