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Gynecologic Oncology 109 (2008) 370 376

www.elsevier.com/locate/ygyno

Do clear cell ovarian carcinomas have poorer prognosis compared to other

epithelial cell types? A study of 1411 clear cell ovarian cancers
John K. Chan a,, Deanna Teoh a , Jessica M. Hu a , Jacob Y. Shin a ,
Kathryn Osann c , Daniel S. Kapp b
a

Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco School of Medicine,
UCSF Helen Diller Family Comprehensive Cancer Center, 1600 Divisadero Street Box 1702, San Francisco, CA 94143-1702, USA
b
Department of Radiation Oncology, Stanford University School of Medicine, Stanford Cancer Center, 300 Pasteur Drive, HH333, Stanford, CA 94305, USA
c
Division of Hematology/Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine Medical Center,
101 The City Drive, Orange, California 92868, USA
Received 12 December 2007
Available online 18 April 2008

Abstract
Objective. To compare the clinico-pathologic characteristics and survival of women with clear cell versus other epithelial ovarian cancers.
Methods. Data were obtained from the Surveillance, Epidemiology and End Results Program between 1988 and 2001 and analyzed using
KaplanMeier and Cox proportional hazards models.
Results. Of 28,082 women with epithelial ovarian cancer, 1411 (5%) had clear cell, 13,835 (49.3%) papillary serous, 3655 (13%) endometrioid,
2711 (9.7%) mucinous, and 6470 (23%) had unspecified histologies. The median age of overall patients was 64 years; with clear cell patients
presenting at younger age (55 years). The proportion of clear cell histology was significantly higher in Asians versus Whites, Blacks, and others
(11.1% versus 4.8%, 3.1%, and 5.5%; p b 0.001). Clear cell carcinoma is more likely to be diagnosed at early-stage (67.3%) compared to 19.2% in
serous, 61.6% endometrioid, and 61.3% in mucinous carcinomas ( p b 0.005). Retroperitoneal lymph node metastases were found in 13.6% of
serous carcinomas, 7.9% clear cell, 7.3% endometrioid, and 3.8% of mucinous ( p b 0.001). Adjusted for stage, the 5-year disease-specific survival
of patients with clear cell carcinoma is worse compared to serous: 85.3% vs. 86.4% for stage I, 60.3% vs. 66.4% stage II, 31.5% vs. 35.0% stage
III, and 17.5% vs. 22.2% for stage IV, respectively ( p b 0.001). On multivariate analysis, age, stage, grade, histology, and surgical treatment were
independent predictors of disease-specific survival.
Conclusions. Our data suggest that women with clear cell ovarian cancer present at a younger age, are more likely to be Asian, and have a
poorer prognosis compared to serous cancers.
2008 Elsevier Inc. All rights reserved.
Keywords: Ovarian cancer; Clear cell; Epithelial carcinomas; Prognosis

Introduction
Ovarian cancer is the fourth most common gynecologic
cancer in the United States, but accounts for the leading cause
of gynecologic cancer deaths. It is estimated that 22,430 new
cases will be diagnosed in 2007, with 15,280 deaths [1]. The
majority of epithelial ovarian cancers will be of serous

Corresponding author. Fax: +1 415 885 3586.

E-mail address: chanjohn@obgyn.ucsf.edu (J.K. Chan).
0090-8258/$ - see front matter 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.ygyno.2008.02.006

histology and diagnosed in advanced stages. Histologic cell

type has been recognized as an important prognostic factor in
ovarian cancer.
Prior reports have shown that clear cell cancers comprise
approximately 5% of all epithelial ovarian cancers. In contrast
to serous cancers, the majority of clear cell adenocarcinomas are
diagnosed at an early stage; however, the prognostic advantage
of this remains unclear. Although a number of reports have
shown similar survival rates for serous compared to clear cell
ovarian carcinomas [25], others have found that clear cell
carcinomas are a more aggressive histologic subtype [68].

J.K. Chan et al. / Gynecologic Oncology 109 (2008) 370376

These reports have revealed that clear cell cancers have a

distinct, aggressive biologic behavior with poor response to
platinum-based therapy compared to their other epithelial
counterparts. However, most of these studies originate from
single-institutions and are limited by a small sample size. In this
current population-based study of 1411 clear cell cancer patients,
we propose to evaluate whether clear cell ovarian carcinomas
have a poorer prognosis compared to other epithelial ovarian
carcinomas.
Materials and methods
Women diagnosed with clear cell ovarian carcinoma between 1988 and 2001
were identified from the Surveillance, Epidemiology and End Results (SEER)
database. During this time period, 26,671 patients with serous, endometrioid,

371

mucinous or other type of epithelial ovarian carcinoma were used for

comparison. Data are reported from twelve population-based registries that
represent approximately 26% of the U.S. population: San FranciscoOakland,
Connecticut, metropolitan Detroit, Hawaii, Iowa, New Mexico, Seattle (Puget
Sound), Utah, metropolitan Atlanta, Alaska, San JoseMonterey, and Los
Angeles. To better characterize our patient population, the race classifications of
the SEER program were categorized into four groups: Whites, Blacks, Asians
and Others. Asians were arbitrarily defined as Chinese, Japanese, Korean,
Vietnamese, and Filipina. All other race and ethnicity classifications were
defined as Others. The ICD-O-3 histology codes used were serous (84418442,
84608462), clear cell (83108313), endometrioid (83808383), and mucinous
(84708482). Ovarian clear cell cancers were compared to serous, endometrioid, and mucinous tumors. Uterus-sparing surgeries were defined as minimal
surgeries that did not include a hysterectomy. Standard surgeries were classified
as those including a hysterectomy and/or debulking. The Institutional Review
Board by Stanford University approved this study. Data including age at
diagnosis, race, extent of surgery, stage of disease, histology, and survival were

Table 1
Characteristics of epithelial ovarian cancer by cell type
Characteristics
Age at diagnosis
Median
Range
Median year of diagnosis
Race a
White
Black
Asian
Other
Stage at diagnosis a
Stage I
Stage IA
Stage IB
Stage IC
Stage II a
Stage IIA
Stage IIB
Stage IIC
Stage III a
Stage IIIA
Stage IIIB
Stage IIIC
Stage IV
Grade
Grade 1
Grade 2
Grade 3
Unknown grade
Surgery a
No surgery
Uterus-sparing b
Standard c
Lymphadenectomy
Yes
No
Unknown
Median no. nodes resected
Presence of positive nodes
Yes
No
Unknown
a
b
c

Total (n = 28,082)
No. (%)

Serous (n = 13,835)
No. (%)

Endometrioid (n = 3655)
No. (%)

Mucinous (n = 2711)
No. (%)

Clear cell (n = 1411)

No. (%)

64
(12101)
1995

64.0
(12101)
1995

56.0
(1894)
1995

58.0
(1497)
1994

55.0
(1294)
1996

24,357 (86.7%)
1631 (5.8%)
1488 (5.3%)
546 (1.9%)

12,219 (88.3%)
730 (5.3%)
605 (4.4%)
250 (1.8%)

3162 (86.5%)
158 (4.3%)
244 (6.7%)
82 (2.2%)

2268 (83.7%)
193 (7.1%)
177 (6.5%)
68 (2.5%)

1164 (82.5%)
50 (3.5%)
165 (11.7%)
30 (2.1%)

p b 0.001

6257 (22.3%)
3710 (13.2%)
396 (1.4%)
1831 (6.5%)
2296 (8.2%)
605 (2.2%)
735 (2.6%)
868 (3.1%)
10,082 (35.9%)
534 (1.9%)
761 (2.7%)
5434 (19.4%)
9447 (33.6%)

1659 (12.0%)
812 (5.9%)
179 (1.3%)
587 (4.2%)
990 (7.2%)
250 (1.8%)
273 (2.0%)
425 (3.1%)
6320 (45.7%)
294 (2.1%)
461 (3.3%)
3627 (26.2%)
4866 (35.2%)

1718 (47.0%)
1042 (28.5%)
123 (3.4%)
474 (13.0%)
532 (14.6%)
183 (5.0%)
205 (5.6%)
130 (3.6%)
869 (23.8%)
83 (2.3%)
103 (2.8%)
476 (13.0%)
536 (14.7%)

1483 (54.7%)
1090 (40.2%)
53 (2.0%)
274 (10.1%)
179 (6.6%)
52 (1.9%)
66 (2.4%)
54 (2.0%)
574 (21.2%)
48 (1.8%)
65 (2.4%)
246 (9.1%)
475 (17.5%)

795 (56.3%)
484 (34.3%)
21 (1.5%)
262 (18.6%)
155 (11.0%)
47 (3.3%)
49 (3.5%)
56 (4.0%)
295 (20.9%)
21 (1.5%)
23 (1.6%)
184 (13.0%)
166 (11.8%)

p b 0.001
p b 0.001

2395 (8.5%)
5114 (18.2%)
12,344 (44.0%)
8229 (29.3%)

747 (5.4%)
2625 (19.0%)
7250 (52.4%)
3213 (23.2%)

710 (19.4%)
1217 (33.3%)
1277 (34.9%)
451 (12.3%)

803 (29.6%)
715 (26.4%)
426 (15.7%)
767 (28.3%)

31 (2.2%)
183 (13.0%)
455 (32.2%)
742 (52.6%)

p b 0.001

5145 (18.3%)
4272 (15.2%)
18,649 (66.4%)

1384 (10.0%)
2111 (15.3%)
10,336 (74.7%)

53 (1.5%)
569 (15.6%)
3033 (83.0%)

255 (9.4%)
654 (24.1%)
1802 (66.5%)

34 (2.4%)
165 (11.7%)
1212 (85.9%)

p b 0.001

7718 (27.5%)
18,541 (66.0%)
1823 (6.5%)
7

3771 (27.3%)
9161 (66.2%)
903 (6.5%)
6

1638 (44.8%)
1742 (47.7%)
275 (7.5%)
9

856 (31.6%)
1689 (62.3%)
166 (6.1%)
7

659 (46.7%)
611 (43.3%)
141 (10.0%)
8

p b 0.001

2754 (9.8%)
6048 (21.5%)
19,280 (68.7%)

1886 (13.6%)
2379 (17.2%)
9570 (69.2%)

267 (7.3%)
1608 (44.0%)
1780 (48.7%)

104 (3.8%)
886 (32.7%)
1721 (63.5%)

112 (7.9%)
669 (47.4%)
630 (44.6%)

p b 0.001

Numbers do not add up to 100% due to small numbers of patients with unknown status.
Uterus-sparing surgeries, including minimal surgery or surgeries that did not include a hysterectomy.
Standard surgeries, including surgeries including a hysterectomy and/or debulking.

p-value

372

J.K. Chan et al. / Gynecologic Oncology 109 (2008) 370376

recorded for analysis. Disease-specific survival probability was calculated using

the KaplanMeier method. Differences between groups were calculated using
the log-rank test. The Cox proportional hazards model was used to assess the
significance of multiple variables simultaneously. P-values b 0.05 were
considered statistically significant.

Results
From 1988 to 2001, 28,082 women were diagnosed with
epithelial ovarian cancer. The largest subgroup, 13,835 (49.3%)
of patients had serous histology. 1411 (5%) were of clear cell
histology; of the remainder, 3655 (13%) were endometrioid,
2711 (9.7%) mucinous, and for 6470 (23%) histology was
not specified. Demographics of the study population are as
summarized in Table 1. Compared to serous cancer patients, the
median age at diagnosis was significantly younger for those
with clear cell carcinoma: 55 years vs. 64 years ( p b 0.001).
Patients with clear cell carcinoma were more likely to be Asian;
in fact, the proportion of Asians, Whites, and Blacks with
clear cell histology was 11.1%, 4.8%, and 3.1%, respectively
( p b 0.001).
Women with clear cell carcinoma were significantly more
likely to be diagnosed with stage III disease compared to serous
cancers (67.3% for clear cell and 19.2% for serous; p b 0.001).
More specifically, over half (56.3%) of clear cell cancers were
found with stage I disease (Table 1). Patients with clear cell
carcinoma were more likely to undergo primary surgery, 85.9%
compared to 66.5%, 74.7%, and 83% of mucinous, serous, and
endometrioid cancer patients ( p b 0.001). Of the entire study
group, 27.5% underwent lymph node dissection, and the median
number of resected nodes was 7 (range: 190). Of those patients,
9.8% (n = 2,754) had nodal involvement. Retroperitoneal lymph
node involvement was present in 7.9% of clear cell carcinomas,
13.6% serous carcinomas, 7.3% endometrioid carcinomas, and
3.8% mucinous carcinomas ( p b 0.001). Of all patients who
underwent a lymphadenectomy, 35.7% had positive lymph
nodes. In women with serous, endometrioid, mucinous, and
clear cell histologies, 50.0%, 16.3%, 12.1%, and 17.0% had
nodal involvement, respectively.
In the overall study group, the 5-year disease-specific
survival of women 64 years versus N 64 years was 56.7%
versus 31.8% ( p b 0.001). Whites, Blacks, and Asians had
corresponding disease-specific survivals of 44.6%, 40.7%, and
54.6%, respectively ( p b 0.001). Women with stage I, II, III, and
IV disease had 5-year disease-specific survivals of 88.3%,
65.0%, 34.1%, and 19.7% ( p b 0.001). Those with grade 1 had
disease-specific survivals of 83.5% compared to 56.4% and
36.5% in grade 2 and 3 disease ( p b 0.001). The number of
lymph node metastases (1, 25, N 5 nodes) was associated with
a worsened disease-specific survival of 41.4%, 37.1%, and
36.0%, though not statistically significant ( p = 0.062).
Across all stages, the overall 5-year disease-specific survival
of clear cell cancer patients was higher at 64.5% compared to
39.4% for serous, 72.5% for endometrioid, and 68.1% for
mucinous cancers ( p b 0.001); however, after adjusting for stage
of disease, clear cell carcinomas had a poorer overall prognosis
( p b 0.001 for stages IIV) (Table 2; Figs. 1AD). Adjusted for
stage, the 5-year disease-specific survival of patients with clear

Table 2
Five-year disease-specific survival by cell type
Characteristics

Total

Overall
45.1%
Age at diagnosis
Age 64
56.7%
Age N 64
31.8%
Race
White
44.6%
Black
40.7%
Asian
54.6%
Other
49.5%
Stage at diagnosis
Stage I
88.3%
Stage IA 93.2%
Stage IB 90.0%
Stage IC 78.4%
Stage II
65.0%
Stage IIA 76.5%
Stage IIB 66.9%
Stage IIC 55.6%
Stage III
34.1%
Stage IIIA 44.7%
Stage IIIB 41.9%
Stage IIIC 35.9%
Stage IV
19.7%
Grade
Grade 1
83.5%
Grade 2
56.4%
Grade 3
36.5%
Surgery
No surgery
9.2%
Uterus50.5%
sparing a
Standard b
51.6%

Serous Endometrioid Mucinous Clear

cell

Logrank

39.4% 72.5%

68.1%

64.5% p b 0.001

48.1% 78.2%
29.8% 59.3%

77.4%
52.8%

66.5% p b 0.001
59.4% p b 0.001

39.0%
41.1%
43.0%
33.9%

72.8%
58.9%
74.0%
82.1%

68.5%
58.0%
78.1%
66.8%

64.8%
41.7%
60.2%
41.2%

p b 0.001
p b 0.001
p b 0.001
p b 0.001

86.4%
91.0%
93.7%
77.7%
66.4%
77.0%
66.0%
61.1%
35.0%
48.7%
41.6%
35.5%
22.2%

92.7%
94.8%
91.2%
89.2%
81.9%
80.7%
82.1%
82.9%
50.6%
60.0%
57.8%
49.7%
34.6%

93.1%
94.9%
91.3%
86.7%
61.3%
76.6%
57.9%
54.3%
34.5%
47.0%
38.8%
34.8%
21.6%

85.3%
91.6%
56.3%
77.3%
60.3%
66.9%
69.5%
45.6%
31.5%
43.9%
20.4%
31.4%
17.5%

p b 0.001
p = 0.001
p b 0.001
p b 0.001
p b 0.001
p = 0.104
p = 0.003
p b 0.001
p b 0.001
p = 0.093
p = 0.004
p b 0.001
p b 0.001

75.7% 93.4%
43.6% 79.2%
34.6% 55.5%

85.6%
70.7%
37.0%

75.4% p b 0.001
75.6% p b 0.001
51.0% p b 0.001

11.8% 40.6%
38.4% 79.1%

8.1%
76.6%

27.8% p = 0.007
66.2% p b 0.001

42.7% 71.7%

71.3%

65.2% p b 0.001

Uterus-sparing surgeries, including minimal surgery or surgeries that did not

include a hysterectomy.
b
Standard surgeries, including surgeries including a hysterectomy and/or
debulking.

cell carcinoma is worse compared to serous: 85.3% vs. 86.4%

for stage I, 60.3% vs. 66.4% for stage II, 31.5% vs. 35.0% stage
III, and 17.5% vs. 22.2% stage IV, respectively ( p b 0.001).
On multivariate analysis, older age at diagnosis ( p b 0.001),
advanced stage ( p b 0.001), higher grade of disease ( p b 0.001),
lack of surgery ( p b 0.001), and clear cell histology ( p b 0.001)
were all independent predictors for poorer survival (Table 3).
Discussion
Since 1973, clear cell ovarian carcinoma has been recognized by the World Health Organization as a distinct histologic
subtype of ovarian cancer. Unlike other epithelial ovarian
cancers, clear cell carcinomas have a greater tendency to present
with a large, unilateral pelvic mass in early stage, be associated
with thromboembolic complications and paraneoplastic syndromes [28]. Given that clear cell cancers are more likely to
present at early stage but display aggressive behavior, it is
unclear if these tumors portend for a poorer prognosis.
A prior study of 44 women with clear cell cancers showed
that these patients have a poorer survival compared to serous

J.K. Chan et al. / Gynecologic Oncology 109 (2008) 370376

cancers, despite the fact that clear cell tumors are more likely to
present at early stage (51% vs. 31%) [6]. This report also found
that clear cell tumor recurrences were more likely to involve
lymph nodes and parenchymal organs. However, this study
included only 44 women and extended from 1944 to 1981.
Moreover, others have also shown that advanced clear cell

373

tumors are more platinum-resistant. These investigators found

that only 45% of patients with clear cell cancers respond to
platinum-based chemotherapy versus 81% in other epithelial
cell types [9]. Similarly, another study showed that of
24 women with stage III clear cell ovarian cancer treated with
platinum-based chemotherapy, 70% had progression of disease

Fig. 1. A. KaplanMeier analysis of stage I patients based on histology. B. KaplanMeier analysis of stage II patients based on histology. C. KaplanMeier analysis of
stage III patients based on histology. D. KaplanMeier analysis of stage IV patients based on histology.

374

J.K. Chan et al. / Gynecologic Oncology 109 (2008) 370376

Fig. 1 (continued ).

while receiving chemotherapy, compared to only 29% of

patients with papillary serous tumors [10]. Furthermore,
nonplatinum-based chemotherapy did not provide any additional benefit in these clear cell ovarian cancer patients. In
a retrospective study from Roswell Park Cancer Institute,
40 patients with clear cell cancers who received platinum-based
chemotherapy were compared with 71 clear cell cancer patients

who received nonplatinum-based chemotherapy. The 5-year

survival rates for the two groups were not different; 36% vs.
32%, respectively ( p = 0.23)[11]. The cause of this relative
chemoresistance is unknown, however a study by Itamochi et al.
showed that clear cell cancers had significantly lower proliferation rates compared to serous adenocarcinomas, which
may partially explain the clear cell tumors' lack of response to

J.K. Chan et al. / Gynecologic Oncology 109 (2008) 370376

Table 3
Multivariate analysis for disease-specific survival

Age at diagnosis a
Stage of disease
Grade
Histology
Surgical treatment b
a
b

Hazard ratio

Confidence interval

p-value

1.02
1.89
1.02
1.05
0.49

(1.021.03)
(1.851.92)
(1.011.03)
(1.041.06)
(0.470.51)

p b 0.001
p b 0.001
p b 0.001
p b 0.001
p b 0.001

Continuous.
No vs. yes (uterine-sparing, hysterectomy, debulking).

chemotherapy [12]. Sugiyama et al. also found that clear cell

cancers are a more aggressive histologic subtype and further
studies are required to define the optimal post-operative
treatment [8]. Furthermore, two recent studies examining
patients with all histologies treated in similar manner, also
showed a worse survival for clear cell compared with serous and
endometrioid histologies [13,14].
Other studies have not found clear cell carcinoma to have a
poorer prognosis compared to other epithelial cell types.
Kennedy et al. compared 29 cases of clear cell adenocarcinoma
with 305 cases of non-clear cell carcinomas and found no
survival difference for overall stage I and II disease [15].
Another study by Crozier et al. reviewed 59 patients with
ovarian clear cell adenocarcinoma and showed that clear cell
cancers were not different from other epithelial ovarian cancers
[2]. Interestingly, they also showed that clear cell cancer
patients with fewer than 10 mitoses per 10 high-power field and
less than 50% solid areas had significantly longer disease-free
intervals. Likewise, Kennedy et al. reviewed 64 patients and
concluded that the survival of clear cell carcinoma patients,
controlled for grade and stage of disease, was not different than
women with other cell types [4]. Similarly, Leitao et al.
performed a clinico-pathologic study of early-stage ovarian
cancer of 25 cases of clear cell carcinomas [5]. These authors
found no significant differences in prognosis when comparing
clear cell carcinoma to the non-clear cell epithelial ovarian
cancers. However, these authors acknowledged that the lack of
difference may be due to the relatively small number of cases.
Since clear cell carcinomas are an uncommon histologic
subtype, accounting for only 5% of all epithelial ovarian
cancers, a large sample size is required to detect significant
differences in outcomes. This current large population-based
study compared 1,411 cases of clear cell carcinoma to over
20,000 control cases of other epithelial cell types. On initial
analysis, the overall 5-year survival rate for clear cell carcinoma
was significantly higher compared to serous carcinomas, due to
the earlier stage at diagnosis of clear cell cancers. However,
after adjusting for stage, those with stage I, II, III, and IV clear
cell cancers have a worse 5-year disease-specific survival at
85.3%, 60.3%, 31.5%, and 17.5% compared to 86.4% 66.4%,
35.0%, and 22.2% in serous cancer patients (Stage I, p b 0.985;
Stage II, 0.314; Stage III, p b 0.001; Stage IV, p b 0.001). In
addition, there was a significantly poorer 5-year disease-specific
survival rate associated with clear cell versus other cell types
across all stages (Table 2; Figs. 1AD).

375

This current study is one of the largest series to date of

unselected patients encompassing 12 regions in the United
States. As such, this cohort of patients is not limited by the
selection and surveillance biases often associated with clinical
trial and studies from single academic institutions. In addition,
the demographic and clinico-pathologic data obtained from this
report are a close reflection of the trends and outcomes of U.S.
women who receive medical care from community hospitals
based on diagnoses from contributing pathologists rather than
academic gynecologic pathologists. The SEER program's
quality control maintains a high level quality and complete
data certification reported by the Northern American Association of Central Cancer Registries. More specifically, the quality
assurance program includes an annual review the medical
records of sample cases for accuracy. Virnig et al. reported a
98% completeness in each sample case with a N 90% rate in the
accuracy of reporting adjuvant radiation therapy [16].
This large population-based series, like others, was restricted
by a lack of central pathology review. To see if there existed any
significant disagreements between registry and referral pathologists, Piver et al., reviewed a large cancer registry's slides and
discovered a 95.3% agreement between pathologists on the
disease site of origin [17]. Furthermore, there was a 61.7%
agreement on histopathology, with only 1% of cases characterized by major differences. Likewise, Tyler et al. reviewed the
slides of 477 women diagnosed with ovarian, breast or endometrial cancer [18]. After comparing the diagnoses of SEERaffiliated pathologists to an expert panel of three gynecologic
pathologists, they determined overall agreement for all cancers
to be 97%, and for major cellular subtypes of ovarian cancer
such as endometrioid and clear cell carcinoma, 73% and 100%,
respectively [18]. Our conclusions can potentially be misleading if there is an over-reliance on interpreting the p-values for
each subgroup. Our analytic approach requires that smaller
subgroups exhibit a much greater benefit than that experienced
by their larger cohorts in order to attain statistical significance.
For example, even though we showed a statistically insignificant +4.8% survival improvement in the small subgroup of
patients with stage IIIA ovarian patients with serous vs. clear
cell, this finding may still suggest a clinically meaningful
improvement because the overall survival of advanced
epithelial ovarian cancer patients is so poor. On the other
hand, we showed a + 3.5% statistical benefit in stage III patients
with serous vs. clear cell. Other major limitations of our study
include the lack of data on treating surgeon's specialty, amount
of residual disease after surgical debulking and information on
chemotherapy.
In conclusion, our data suggest that women with clear cell
ovarian carcinoma are likely to be younger, of Asian descent,
and present at an earlier stage than other epithelial ovarian
cancers. Clear cell tumors portend for a poorer survival after
adjusting for stage of disease and other prognostic factors such
as age and grade of disease. To our knowledge there are no
randomized clinical trials that have definitively shown that
different treatment regimens for clear cell cancers of the ovary
versus other epithelial cell types can improve survival outcomes. However, there are many retrospective series that have

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J.K. Chan et al. / Gynecologic Oncology 109 (2008) 370376

reported on the potential benefit of various chemotherapeutic

combinations[1921]. Recently, our group has proposed a
clinical trial using novel targeted agents against VEGF (vascular
endothelial growth factor) and PDGF (platelet-derived growth
factor) in the treatment of recurrent and persistent ovarian clear
cell cancers. Translational studies are clearly warranted to
identify the molecular pathways unique to this cell type in order
to design novel biologic agents to overcome the drug resistance
of this aggressive cancer[22,23].
Conflict of interest statement

[11]

[12]

[13]

[14]

The authors declare that there are no conflicts of interest.

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