Ji Young Lee, MD, PhD, David Marchetti, MD, M Steven Piver, MD

Department of Obstetrics and GynecologySisters of Charity Hospital, Buffalo, NY

The Clinical significance of DNA ploidy

as a prognostic factor in patients with

Borderline Ovarian TumorRetrospective study

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 tumorMean age 45.7 yr

75% of tumors are Stage I5 YSR for early stage tumors ≥

95%Recurrence rate 8~32%Risk factors for recurrence

FIGO stage, Age, Residual disease, Histology,

DNA ploidy etc.

DNA PloidyDNA 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

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

OBJECTIVES

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 Cytometryby USLABS (Irvine, CA)

Diploid ( DI=1.0, single peak)

Aneuploid (DI;1.1-1.9), Multi-peak

RESULTS ….and DISCUSSION

0

1

2

3

4

5

6

7

8

20-29 30-39 40-49 50-59 60-69 70-79 80-89

Age Distribution of Borderline Ovarian Tumor

Age

MEAN AGE 54.5 yo

Pati

ents

(N

o.)

Age distribution of Borderline Ovarian Age distribution of Borderline Ovarian TumorTumor

Sep 1993 – Sep 2004 in SwedenSep 1993 – Sep 2004 in Sweden

Int J Gynecol Cancer 2008;18:453–459.

0

1

2

3

4

5

20-29 30-39 40-49 50-59 60-69 70-79 80-89

Pati

ents

(N

o.)

Age

Histology and Age Distribution of Borderline Ovarian Tumor

Serous

Mixed

Mucinous

0

1

2

3

4

5

6

20-29 30-39 40-49 50-59 60-69 70-79 80-89

Diploid

Aneuploid

Age

Pati

ents

(N

o.)

DNA Ploidy and Age at DNA Ploidy and Age at Diagnosis Diagnosis

The relationship of Histopathology

and FIGO stage of disease Stage (%) Total IA IB IC II III NA Serous 8(50%) 1(8%) 4(21%) 0 3(21%) 0 16 Mucinous 4(50%) 1 0 1 1 1 8 Mixed 2 1 0 1 0 2 6 Total 14 3 4 2 4 3 30

The relationship of DNA ploidy and

Histology of disease

Histology Total DNA ploid Serous Mucinous Mixed Aneuploidy 4 (45%) 2 (22%) 3 (33%) 9 (100%) Diploidy 12 (58%) 6 (28%) 3 (14%) 21 (100%)

0

2

4

6

8

10

12

14

Serous-Diploid Serous-Aneuploid Mucinous-Diploid Mucinous-Aneuploid

Mixed-Diploid Mixed-Aneuploid

58%

28%

14%

DNA ploidy and Histologic type

Histology-DNA Ploidy

Pati

ents

(N

o.)

The relationship of DNA ploidy and

FIGO stage of disease DNA ploid Aneuploidy Diploidy FIGO Stage IA 2 12 IB 1 2 IC 2 2 II 1 1 III 2 2 Unstaged 1 2

Total 9 (30%) 21 (70%)

DNA Ploidy and Disease Stage

Diploid

AneuploidPati

ents

(N

o.)

Stage-DNA Ploidy

0

2

4

6

8

10

12

14

Characteristics of 30 patients

Characteristics TOTAL Diploid Aneuploid p value (n=30) (n=21) (n=9) Age < 50 11 5 6 0.09 ≥ 50 19 16 3 Ethnicity Caucasian 29 21 8 0.002 African-American 1 1 FIGO Stage IA 14 12 2 0.007 IB 3 2 1 IC 4 2 2 II-III 6 3 3 Unstaged 3 2 1 Pelvic Cytology positive 6 4 2 0.1 Negative 24 17 7 Histology Serous 16 12 4 0.4 Mucinous 8 6 2 Mixed 6 3 3 Chemotherapy Yes 4 3 1 No 26 18 8

HistologyBorderline Ovarian Tumor

Tropé CG. Seminars in surgical oncology 2000 9(1)69 –75

The relation of histopathology to ploidy status

Histopathology Number Diploid Aneuploid No FCM of cases (%)

Serous 219 (54.9) 167 27 25Mucinous 171 (42.9) 127 32 12Endometrioid 5 (1.2) 3 2 —Clear cell 1 (0.2) — 1 —Mixed 3 (0.8) 2 1 —

Total 399 299 63 37

Int J Gynecol Cancer 2008;18:453–459.

N Recurred DiedStage I 686 29 9Stage II & III 219 40 22Total 905 69(7.6%)

31(3.4%) Rubin SC, Sutton GP (2001,Ovarian cancer 2nd edition)

Overall Recurrence and survival

in Borderline ovarian tumor

DNA Ploidy and Prognosis in Borderline Ovarian Tumor

(I)

Cancer 1992 69(10): 2510

Seidman JD et al. Cancer 1993;71:12

…DNA ploidy may be of little prognostic

importanceHarlow BL et al. Gynecol Oncol 1993;50:305

…No correlation between DNA ploidy and Survival or Recurrence

DNA Ploidy and Prognosis in Borderline Ovarian Tumor

(II)

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

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ACKNOWLEDGEMENT

M Steven Piver, MDDavid Marchetti, MD

Judine Davis, MDAnthony Pivarunas, DOPathology Department

USLABS, CA