1 23

Medical Oncology ISSN 1357-0560 Med OncolDOI 10.1007/s12032-012-0165-4

Comparative analysis of CA 125, ferritin,beta-2 microglobulin, lactic dehydrogenaselevels in serum and peritoneal fluid inpatients with ovarian neoplasia

Umran Kucukgoz Gulec, Semra Paydas,Ahmet Baris Guzel, Selim Buyukkurt,Gulsah Seydaoglu & Mehmet Ali Vardar

1 23

Your article is protected by copyright and

all rights are held exclusively by Springer

Science+Business Media, LLC. This e-offprint

is for personal use only and shall not be self-

archived in electronic repositories. If you

wish to self-archive your work, please use the

accepted author’s version for posting to your

own website or your institution’s repository.

You may further deposit the accepted author’s

version on a funder’s repository at a funder’s

request, provided it is not made publicly

available until 12 months after publication.

ORIGINAL PAPER

Comparative analysis of CA 125, ferritin, beta-2 microglobulin,lactic dehydrogenase levels in serum and peritoneal fluidin patients with ovarian neoplasia

Umran Kucukgoz Gulec • Semra Paydas •

Ahmet Baris Guzel • Selim Buyukkurt •

Gulsah Seydaoglu • Mehmet Ali Vardar

Received: 29 December 2011 / Accepted: 7 January 2012

� Springer Science+Business Media, LLC 2012

Abstract The aim of this study was to investigate the

diagnostic role of the CA 125, ferritin, beta-2 microglobulin

(b2 M), and lactic dehydrogenase (LDH) levels in serum and

peritoneal fluid (PF) in patients with ovarian neoplasms.

Using cross-sectional study design; serum and PF CA 125,

ferritin, b2 M, and LDH levels were analyzed in 40 patients

with benign ovarian neoplasms (Group 1) and 59 patients with

malignant ovarian neoplasms (Group 2) which were evalu-

ated surgically. Serum and PF levels of these markers com-

pared between the groups. Diagnostic role of these markers

were determined with receiver operating curve (ROC) anal-

ysis. Serum and PF CA 125, ferritin, b2 M, and LDH levels

were statistically significant higher in patients with ovarian

cancers as compared with benign neoplasms. Among these

biomarkers, PF b2 M levels had highest sensitivity and

specificity, 76.3 and 85%, respectively with the cut-off value:

2.3 mg/l. This study results indicates that especially PF b2 M

and ferritin levels may be valuable for diagnosis of malignant

ascites in patients with ovarian neoplasms.

Keywords CA 125 � Beta 2 microglobulin � Ferritin �Lactic dehydrogenase � Ovarian neoplasia

Introduction

Among gynecologic cancers, ovarian cancer is the most

common cause of mortality. These cancers are detected in

late stages and 5 year overall survival (OS) rates of these

cases are below 20% [1]. Efforts are ongoing to discover

new biomarkers to diagnose this disease in earlier stages.

For this reason, various circulating markers have been

identified and quantified in blood, peritoneal fluid (PF) or

homogenized tissue samples [2]. These biomarkers could

be useful to distinguish malignant ovarian neoplasms from

benign neoplasms and also to determine the prognosis, to

predict response to chemotherapeutics, to detect the relapse

as early as possible. Among the biomarkers used for

epitelial ovarian cancers (EOCs), CA 125 is the most

common studied marker. CA 125 is a high molecular

weight glycoprotein produced by epitelial ovarian tumors

and by mesothelial cells [3]. For this reason, CA 125 has

several limitations to use as a biomarker. On the other

hand, up to 20% of ovarian cancers fail to express high

levels of this marker. Normal levels of CA 125 were

observed in 50% of patients with minimal persistent dis-

ease. Additionally, CA 125 does not always useful to

predict the disease recurrence [4]. Serum CA 125 levels are

found to be increased in the presence of serosal fluids such

as peritoneal, pleural, or pericardial [5]. Due to these rea-

sons, the specificity of CA 125 is low while it is a sensitive

biomarker in epitelial ovarian cancers (EOCs).

Plasma ferritin is secretory component of intracellular

ferritin and it reflects the iron stores. Plasma ferritin levels

can increase in various conditions such as increased

U. Kucukgoz Gulec � A. B. Guzel � S. Buyukkurt �M. A. Vardar

Department of Obstetrics and Gynecology, Faculty of Medicine,

Cukurova University, Adana, Turkey

U. Kucukgoz Gulec (&)

Cukurova Universitesi Tıp Fakultesi Kadın Hastalıkları ve

Dogum A.D., 01330 Adana, Turkey

e-mail: ukucukgoz@yahoo.com

S. Paydas

Department of Medical Oncology, Faculty of Medicine,

Cukurova University, Adana, Turkey

G. Seydaoglu

Department of Biostatistics, Faculty of Medicine,

Cukurova University, Adana, Turkey

123

Med Oncol

DOI 10.1007/s12032-012-0165-4

Author's personal copy

metabolism, inflammation (as an acute phase reactant),

tissue damage and in some neoplastic diseases [6]. Eval-

uation of ferritin as a tumor marker in ovarian malignancy

is still an open question. Lactic dehydrogenase (LDH) is an

enzyme in the glycolytic pathway and it is released as a

response to cell damage. The critical point is the LDH and

isoenzyme analysis may show malignant etiology in pleu-

ral effusions or ascites. The diagnostic and/or prognostic

value of LDH activity in malignant effusions and serum is

controversial in ovarian tumors [7, 8].

Beta 2 microglobulin (b2 M) is a non-glycosylated

polypeptide composed of 100 aminoacids. MHC class 1

molecules consist of heavy chain which contain a1, a2, and

Ig-like domain a3, and a light chain which call b2 M. Best

characterized function of b2 M is to interact with and to

stabilise the tertiary structure of the a-chain. It binds with

the a-chain non-covalently and it can be exchanged with

the circulating form of b2 M. So it is present at low levels

in serum, urine, and other body fluids under physiological

conditions [9]. Although the levels of expression may be

different among the different cells, b2 M and other MHC

class 1 molecules are found in almost all normal nucleated

cells and in the majority of the tumor cells [10]. Some solid

tumors express b2 M on their surface to escape from host

immun surveillance. Overexpression of b2 M has been

reported especially in hematological malignancies [11].

These molecules are potential targets for the antibody-

based therapy for b2 M/MHC class 1-positive tumors.

Diagnostic evaluation of malignant effusions in

abdominal cavity may represent a difficult clinical problem

because the demonstration of malignant cells in effusions is

not always possible. Studies to define accurate discrimi-

natory biochemical markers for malignant effusions have

been so far unsuccessful. In this study we evaluated the

diagnostic value of serum and PF CA 125, ferritin, b2 M

and LDH in patients with surgically managed benign and

malignant ovarian neoplasms. To the best of our knowl-

edge, the present study is first aimed to evaluate the

diagnostic accuracy of PF ferritin and b2 M levels in

patients with ovarian neoplasms.

Material and methods

This study was performed in 99 patients with diagnosed

ovarian tumor and underwent laparotomic surgery in Uni-

versity of Cukurova, School of Medicine, Department of

Gynecologic Oncology between May 2010–June 2011.

Local ethic commitee approved this study and informed

consent was obtained from each case. The patients with

endometriosis, endometrioma, and previous history of

hematologic disorders, immun deficiency, otoimmune dis-

ease, chronic renal disease, infection history in recent days,

lymphoproliferative disease were excluded. Additionally

the patients with metastatic ovarian cancer, received neo-

adjuvant chemotherapy and had no PF for the biomarker

analysis were also excluded form this study. Serum and PF

CA 125, ferritin, b2 M, LDH levels were analyzed in 99

subjects. Forty of these patients had benign (Group 1) and

59 patients had malignant ovarian neoplasms (Group 2).

Group 2 was divided two subgroups as non-epitheloid

ovarian cancer (NEOCs) and EOCs. Histopathological

characteristics of the patients have been shown in Table 1.

In all cases, serum samples for marker measurement were

taken just before the surgical procedure. Blood samples

were collected in a 10 ml tube without any anticoagulant.

PF samples were obtained during laparotomy by aspirating

10 ml ascitic fluid. Irrigation fluid by saline was not used for

analysis. All ovarian cancer patients were staged according

to the International Fedaration of Gynecology and Obstet-

rics (FIGO) classification. In our series all serous adeno-

carcinomas were high grade except one patient who has low

grade, micropapillary subtype. Clear cell, serous plus clear

cell tumors defined high grade EOCs. Ovarian mass volume

and presence of peritoneal carcinomatosis were determined.

Ovarian mass volume was calculated using the prolate

Ellipsoid Formula (L 9 H 9 W 9 0.523) by using histo-

morphometric evaluation reports.

Table 1 The distribution of cases according to their histologic

subtypes

n Percent (%)

Benign ovarian neoplasms 40 40.4

Dermoid cyst 11 11.1

Fibroma 11 11.1

Fibrothecoma 2 2.0

Simple cyst 4 4.0

Struma ovarii 2 2.0

Mucinous cyst adenoma 6 6.0

Serous cyst adenoma 4 4.0

Nonepitheloid malignant neoplasms 12 12.1

Sertoli leydig 2 2.0

Dysgerminoma 2 2.0

Granulosa cell 5 5.0

Immature teratoma 1 1.0

Mixed tumor 2 2.0

Epitheloid malignant neoplasms 47 47.4

Serous 32 34.0

Clear cell 3 3.3

Serous plus clear cell 4 4.0

Serous borderline 2 2.0

Endometrioid 2 2.0

Mixed carcinoma 2 2.0

Undifferentiated 2 2.0

Med Oncol

123

Author's personal copy

CA 125 and ferritin levels of serum and PF of the study

groups were measured with chemiluminescent immunoas-

say kits (OV monitor ref no: 386357 and Ferritin ref no:

33020) by using Beckmann Coulter Access Immunoassay

Systems (CA, USA). b2 M levels of serum and PF, were

measured with immunoturbidometric assay (Beta2 micro

latex Sentinel, ref no: 11505H) by using Beckmann Coulter

UniCel DxC 800 Synchron systems (CA, USA). LDH

levels of serum and PF, were measured with enzymatic

kinetic assay (ref no: 442655) by using Beckmann Coulter

UniCel DxC 800 Synchron systems (CA, USA).

Data are shown as mean ± SD, median, min–max

value. Kruskal–Wallis and Mann–Whitney U tests for

nonparametric data were used to determine the significance

of single and multiple comparisons. Correlations of serum

and PF biomarker levels were made using the Spearman

and Pearson’s correlation coefficients tests. Receiver

Operating Characteristic (ROC) analysis was performed for

evaluated diagnostic values and Area Under Curve (AUC)

were estimated with a 95% confidence interval. For the

prediction of malignancy sensivity and specificity of these

markers at various cut-offs were estimated. Odds ratio

(OR) and confidence interval (CI) were calculated. A sig-

nificance level of 0.05 (two- sided P values \0.05) was

used in all tests. Statistical analyses were carried out using

the Statistical Package for Social Sciences (SPSS version

16.0; SPSS Inc., Chicago, IL, USA).

Results

Serum and PF samples of 99 patients were evaluated for

four markers. The mean age of Group 1 and Group 2 were

49.9 ± 17.5 and 54.6 ± 14.5 years, respectively and there

was no significant difference between the groups (P =

0.143). The mean ovarian volumes were 160.3 ± 216.9 and

165.9 ± 297.7 cm3 in Group 1 and Group 2, respectively

and there was no significant difference (P = 0.919). Ten

patients had stage 1, 9 patients had stage 2, 37 patients had

stage 3, and 3 patients had stage 4 ovarian cancer. Totally

two-thirds of the ovarian cancer patients had stage 3 and 4

(67.7%).

Serum and PF levels of CA 125, b2 M, ferritin and LDH

have been shown in Table 2. Serum and PF marker levels

were found higher in patients with malignant ovarian

tumors as compared with patients with benign tumors and

there was statistically significant difference between the

groups. Additionally higher levels of these markers

observed in EOCs than in NEOCs. There was no statisti-

cally significant difference between serum and PF CA 125,

ferritin and b2 M levels in benign and NEOCs groups.

All patients had higher levels of CA 125, ferritin, b2 M

and LDH in PF compared with serum. A positive

correlations were determined between serum and PF

markers levels except for CA 125 in benign group. Data of

correlation analysis have been shown in Table 3. ROC

analysis of the markers of serum and PF have been shown

in Fig. 1. Table 4 demostrates the AUC,OR, 95% CI

(upper and lower bound levels), P value for OR, cut-off

levels, sensitivity and specificity of the markers both in

serum and PF. Crosstabs and Chi-Square tests were used

for diagnostic accuracy of studied biomarkers and results

have been shown in Table 5.

Discussion

CA 125 is the most commonly used marker in cases with

ascites. Elevated serum CA 125 levels have been reported

in many patients with benign serosal involvement in

addition to the malignant disorders [12, 13]. It is very well

known that quantitative determination and comparison of

circulating tumor markers in serum and PF of patients with

ovarian neoplasms provide the correlation between the

ability to produce these markers and the release of markers

from their place of origine into the circulation [14]. In our

study, highest levels of serum and PF CA 125 were

observed in EOCs patients because all patients with peri-

toneal carcinomatosis were in this group. These results may

be explained by the fact that these patients have widespread

involvement of the peritoneum with tumor and is correlated

with the antigen transfer from the peritoneum to the blood.

Serum CA 125 levels were correlated with PF levels, thus

this study suggests that there is no advantage of PF CA 125

analysis as shown by Tuzun et al. [15].

The value of LDH activity in malignant effusions and

serum is controversial in ovarian tumors. Shnider et al. [7]

studied PF and serum LDH in cases with ovarian cancer,

other gynecologic neoplasms and benign ovarian tumors

and they found that PF LDH levels had higher diagnostic

sensitivity and diagnostic accuracy. Yuce et al. [8] found a

relationship between LDH and advanced stage disease,

aggressive histologic type, higher grade tumor and positive

abdominal cytology in EOCs. Halperin et al. [16] sug-

gested that PF LDH is reliable marker to discriminate the

ovarian cancer from benign ovarian tumors, particularly in

the presence of negative cytology. In summary the

importance of LDH levels in EOCs is not clear. Although

we did not evaluate the isoenzymes of LDH, total LDH

levels in serum and PF were found to be statistically sig-

nificant different between the patients with benign and

malignant ovarian neoplasms.

Ferritin is normally present in the serum and other body

fluids. Several mechanisms may be responsible for the

increased concentrations of ferritin associated with malig-

nant disease. Possible mechanisms for increased ferritin

Med Oncol

123

Author's personal copy

Table 2 The analysis of age, ovarian volume and serum, peritoneal fluid CA 125, ferritin, B2 M, LDH levels

Group 1

n = 40

Group 2

NEOCs

n = 12

Group 2

EOCs

n = 47

Group 2

Total

n = 59

All groups

n = 99

P value

Age (year) 49.9 ± 17.5

51.5 (18–81)

41.3 ± 12.8

44 (14–63)

58.0 ± 12.9

57 (35–85)

54.6 ± 14.5

51 (14–85)

52.7 ± 15.8

51 (14–85)

0.143*

0.001**

Ovarian volume (cm3) 160.3 ± 216.9

91 (1–988)

110.8 ± 133.0

65 (3–489)

181.3 ± 328.9

23.0 (1–1569)

165.9 ± 297.7

32.0 (1–1569)

163.5 ± 265.4

68 (1–1569)

0.919*

0.719**

Serum CA 125

level (IU/l)

51.9 ± 157.1

19.0 (6–1010)

123.3 ± 237.7

28 (9–844)

1045 ± 1662.8

362 (5–8519)

857.9 ± 1530.9

193.0 (5–8519)

532.2 ± 1246.9

46 (5–8519)

0.000*

0.000**

0.250***

0.000****

0.002*****

Peritoneal fluid CA 125

level (IU/l)

1970 ± 3538.1

717.4 (30–13437)

1393 ± 1120.1

1422 (94–3543)

5750 ± 107907

1761 (28–46475)

4863 ± 9783

1750 (28–46475)

3695.0 ± 7979.1

1508.0 (28–46475)

0.001*

0.002**

0.480***

0.000****

0.103*****

Serum ferritin

level (ng/ml)

66.1 ± 73.0

40.9 (12–348)

86.8 ± 129.4

37.3 (7–369)

421 ± 747.9

121.5 (3–3863)

353.1 ± 682.1

91.4 (3–3863)

237.1 ± 545.4

57.4 (3–3863)

0.002*

0.000**

0.508***

0.000****

0.007*****

Peritoneal fluid

ferritin level (ng/ml)

904.4 ± 4186.3

102.0 (16–26574)

1855.4 ± 3796

416.9 (72–12417)

1272.9 ± 1372.0

760.5 (12–6492)

1391.4 ± 2069.3

560 (72–12417)

1194.6 ± 3092.6

367.0 (12–26574)

0.000*

0.000**

0.011***

0.000****

0.071*****

Serum B2 M

level (mg/l)

1.8 ± 0.7

1.6 (1–5)

2.2 ± 0.8

2 (1.0–3.3)

2.9 ± 1.1

2.7 (1.0–7)

2.7 ± 1.1

2.5 (1–7)

2.3 ± 1.0

2.1 (1–7)

0.000*

0.000**

0.090***

0.000****

0.085*****

Peritoneal fluid

B2 M level (mg/l)

1.6 ± 0.9

1.7 (0–4)

1.8 ± 1.3

1.8 (0–4)

3.5 ± 1.1

3.6 (0–6)

3.1 ± 1.3

3.3 (0–6)

2.5 ± 1.4

2.3 (0–6)

0.000*

0.000**

0.536***

0.000****

0.001*****

Serum LDH level

(IU/ml)

366.9 ± 268.1

324 (144–1649)

335.8 ± 148.5

266.5 (157–600)

480.5 ± 245.1

123 (4–1508)

449.1 ± 236.2

430.0 (123–1508)

415.9 ± 251.5

368.0 (123–1649)

0.011*

0.004**

0.974***

0.002****

0.028*****

Peritoneal fluid

LDH level (IU/ml)

508.6 ± 454.3

394 (8–2122)

780.0 ± 535.4

659.0 (220–2068)

987 ± 1005.8

682.5 (192–6432)

945.1 ± 929.4

682.5 (192–6432)

768.7 ± 799.8

521 (8–6432)

0.001*

0.002**

0.046***

0.001****

0.638*****

* Between the group 1 and group 2, Mann–Whitney U Test; ** Between the all groups, Kruskal–Wallis Test; *** Between the group 1 and

NEOCs groups, Mann–Whitney U Test; **** Between the group 1 and EOCs groups, Mann–Whitney U Test; ***** Between the NEOCs and

EOCs groups, Mann–Whitney U Test

Med Oncol

123

Author's personal copy

levels are increased synthesis associated with inflammation

and increased secretion of ferritin by malignant cells and

hepatocellular necrosis caused by liver metastasis.

Increased ferritin concentration may affect the immune

system by altering T-cell function [6]. Yinnon et al. [17]

reported that the serum ferritin, PF ferritin levels and ratios

between them may be useful in the diagnosis of malignant

pleural and peritoneal effusions. High tissue levels of fer-

ritin have been reported in patients with various malig-

nancies. Tripathi et al. [18] reported elevated expression of

ferritin H-chain m RNA in metastatic ovarian tumor. Pinto

et al. [19] reported higher serum ferritin levels in cases

with ovarian cancer as compared with control group. Our

findings support these results but there is conflict with the

findings of another studies. Paydas et al. [20] reported the

lack of difference between fluid and serum levels of ferritin

in cases with benign and malignant effusions and also

another study showed that elevated ferritin concentrations

in effusions are not good parameter to discriminate the

malignant effusions from the benign disorders [21]. To the

best of our knowledge the present study is the first study

showing the diagnostic accuracy of PF ferritin in malignant

ascites with ovarian cancer.

Any change in the MHC profile of tumor cells (includ-

ing classical and nonclassical MHC molecules) may have a

profound influence on the immune recognition and immune

rejection of cancer cells [11]. In the normal human ovary,

surface epithelial cells, mature granulosa cells and lutein

cells reacted with anti HLA-A, B, C and b2 M antibodies

but reacted with anti-Ia (Ia-like, HLA-DR). Stromal cells

and granulosa cells of the primordial follicles did not react

with any of the antibodies. Kababar et al. [22] investigated

the expression of major histocompability antigens and

inflammatory cellular infiltrate in ovarian neoplasms. They

reported that all benign epithelial tumors, 86% of border-

line and 81% of malignant epithelial tumors reacted with

anti-HLA and/or b2 M antibodies. Roland et al. [23]

reported the prognostic potential of HLA class 1 antigen

expression: HLA class 1 heavy chain and b2 M were

studied in 339 tissue samples taken from ovarian cancer

Table 3 Correlation of biomarkers in peritoneal fluid (PF) and serum

Groups CA 125 Ferritin B2 M LDH

Group 1 –0.26 0.51** 0.41** 0.24

Group 2 0.58** 0.27** 0.46** 0.04

Total 0.38** 0.44** 0.43** 0.23**

N:99

** Correlation is significant at the 0.01 level (2-tailed)

Fig. 1 Receiver operating characteristic (ROC) analysis and area

under the curve (AUC) for the serum and peritoneal fluid levels of the

tumor markers. S: Serum analysis of the CA 125, ferritin, B2 M, LDH;

PF: peritoneal fluid analysis of the CA 125, ferritin, B2 M, LDH

Table 4 Sensitivity and specificity of tumor markers in serum and peritoneal fluid

Test result variable(s) AUC P Odds ratio (OR) 95% Confidence interval

Lower Upper Cutoff Sensitivity Specificity

SCA125 0.817 0.000* 11.0 4.2 28.7 34.5 78.0 78.0

Sferritin 0.688 0.002* 3.6 1.5 8.4 55.2 66.1 65.0

SB2 M 0.786 0.000* 5.7 2.3 13.9 2.0 76.3 70.0

SLDH 0.651 317 67.8 50.0

PFCA125 0.689 0.000* 5.3 2.2 12.8 928 76.3 62.5

PFferritin 0.826 0.000* 11.0 4.2 28.7 310 76.3 77.5

PFB2 M 0.835 0.000* 16.6 5.8 47.3 2.3 76.3 85.0

PFLDH 0.706 414 74.6 50.0

S serum analysis of the CA 125, ferritin, B2 M, LDH; PF peritoneal fluid analysis of the CA 125, ferritin, B2 M, LDH. * P value for odds ratio

(OR); CI confidence interval

Med Oncol

123

Author's personal copy

tissue by immunohistochemistry. They found that HLA

class 1 antigen expression was an independent prognostic

marker in ovarian cancers and it was correlated with poor

prognostic outcome. Although b2 M has been studied

extensively in lymphoproliferative disorders, studies about

b2 M in ovarian tumors are very limited and old. We found

an important difference for serum and PF b2 M levels

between benign and malignant ovarian tumors, this is an

important point. Additionally subgroup analysis showed

that the advantage of b2 M measurements in EOCs. When

we take the b2 M levels as 2 and 2.3 in serum and PF, OR

was found to be 5.7 and 16.6, respectively. This finding

suggests that b2 M may be a useful marker in EOCs as

compared with CA 125 and even more powerfull especially

in PF.

Conclusion

In the light of our results serum and especially PF b2 M

and ferritin measurements were found to be valuable. So

far CA 125 is the most important biomarker for EOCs. We

Table 5 Diagnostic accuracy of biomarkers

Group 1 Group 2 NEOC EOC

Serum

SCA 125

? 9.8 (16.7%) 45 (83.3%) 5 (9.3%) 40 (74.1)

- 31 (68.9%) 14 (31.1%) 7 (15.6) 7 (15.6%)

OR (CI) 11.07 (4.2–28.7)* 8 (1.9–32.4)** 19.6 (6.5–58.7)*** 2.4 (0.6–9.6)****

P value 0.001* 0.002** 0.001*** 0.189****

SB2 M

? 12 (22.2%) 42 (77.8%) 6 (11.1%) 36 (66.7%)

- 28 (62.2%) 17 (37.8%) 6 (13.35) 11 (24.4%)

OR (CI) 5.765 (2.3–13.9)* 3.27 (0.8–12.2)** 5.4 (2.1–13.6)*** 2.33 (0.6–8.7)****

P value 0.001* 0.069** 0.001*** 0.202****

Sferritin

? 14 (26.4%) 39 (73.6%) 4 (7.5%) 35 (66.0%)

- 26 (56.5%) 20 (43.5%) 8 (17.4%) 12 (26.1%)

OR (CI) 3.621 (1.5–8.4)* 5.8 (1.4–22.9)** 7.6 (2.9–19.8)*** 0.929 (0.2–3.6)****

P value 0.002* 0.007** 0.001*** 0.915****

Peritoneal fluid

PFCA 125

? 15 (25%) 45 (75%) 7 (15.6%) 38 (84.4%)

- 25 (64.1%) 14 (35.9%9 5 (35.7%) 9 (64.3%)

OR (CI) 5.357 (2.2–12.8)* 3.06 (0.7–11.7)** 7.03 (2.6–18.5)*** 2.3 (0.6–8.6)****

P value 0.001* 0.102** 0.001*** 0.2000****

PFB2 M

? 6 (12%) 44 (88%) 4 (933.3%) 40 (85.1%)

- 34 (69.4%) 15 (30.6%) 8 (66.7%) 7 (14.9%)

OR (CI) 16.6 (5.8–47.3) 11.4 (2.6–48.4)** 32.2 (9.9–105.6)*** 2.8 (0.6–12.4)****

P value 0.001* 0.001** 0.001*** 0.158****

PFferritin

? 9 (16.7%) 45 (76.3%) 7 (15.6%) 38 (84.4%)

- 31 (68.9%) 14 (23.7%) 14 (23.7%) 9 (64.3%)

OR(CI) 11.07 (4.2–28.7)* 3.06 (0.7–11.7)** 14.5 (5.1–41.0)*** 4.8 (1.2–18.9)****

P value 0.001* 0.102** 0.001*** 0.018****

?: positive results, -: negative results

S serum analysis of the CA 125, ferritin, B2 M; PF peritoneal fluid analysis of the CA 125, ferritin, B2 M)

P value by Chi-Square test. * Between Group 1and Group 2;** Between EOCs and NEOCs; *** Between Group 1 and EOCs; **** Between

Group 1 and NEOCs

Med Oncol

123

Author's personal copy

can suggest that b2 M may be a new candidate marker for

EOCs. Of course we need future studies showing the value

of this biomarker and also in prediction of clinical response

and guidance of treatment.

Conflict of interest There are no conflicts of interest.

References

1. Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;351(24):

2519–29.

2. Rein BJ, Gupta S, Dada R, Safi J, Michener C, Agarwal A.

Potential markers for detection and monitoring of ovarian cancer.

J Oncol. 2011;2011:475983.

3. Zeimet AG, Marth C, Offner FA, Obrist P, Uhl-Steidl M,

Feichtinger H, et al. Human peritoneal mesothelial cells are more

potent than ovarian cancer cells in producing tumor marker

CA-125. Gynecol Oncol. 1996;62:384–9.

4. Rosen DG, Wang L, Atkinson JN, Yu Y, Lu KH, Diamandis EP,

et al. Potential markers that complement expression of CA125 in

epithelial ovarian cancer. Gynecol Oncol. 2005;99(2):267–77.

5. Molina R, Filella X, Jo J, Ballesta AM. CA 125 in biological

fluids. Int J Biol Markers. 1998;13:224–30.

6. Finch CA, Bellotti V, Stray S, Lipschitz DA, Cook JD, Pippard

MJ, Huebers HA. Plasma ferritin determination as a diagnostic

tool. West J Med. 1986;145(5):657.

7. Schneider D, Halperin R, Langer R, et al. Peritoneal fluid lactate

dehydrogenase in ovarian cancer. Gynecol Oncol. 1997;66:

399–404.

8. Yuce K, Baykal C, Genc C, Al A, Ayhan A. Diagnostic and

prognostic value of serum and peritoneal fluid lactate dehydro-

genase in epithelial ovarian cancer. Eur J Gynecol Oncol. 2001;

22(3):228–32.

9. Yewdell JW, Reits E, Neefjes J. Making sense of mass destruc-

tion: quantitating MHC class I antigen presentation. Nat Rev

Immunol. 2003;3:952–61.

10. Algarra I, Collado A, Garrido F. Altered MHC class I antigens in

tumors. Int J Clin Lab Res. 1997;27:95–102.

11. Cabrera T, Lopez-Nevot MA, Gaforio JJ, Ruiz-Cabello F, Garr-

ido F. Analysis of HLA expression in human tumor tissues.

Cancer Immunol Immunother. 2003;52(1):1–9.

12. Sevinc A, Buyukberber S, Sari R, Kiroglu Y, Turk HM, Ates M.

Elevated serum CA-125 levels in hemodialysis patients with

peritoneal, pleural, or pericardial fluids. Gynecol Oncol. 2000;77:

254–7.

13. Buamah P. Benign conditions associated with raised serum CA-

125 concentration. J Surg Oncol. 2000;75:264–5.

14. Sedlaczek P, Frydecka I, Gabrys M, Van Dalen A, Einarsson R,

Harłozinska A. Comparative analysis of CA125, tissue polypep-

tide specific antigen, and soluble interleukin-2 receptor alpha

levels in sera, cyst, and ascitic fluids from patients with ovarian

carcinoma. Cancer. 2002;95(9):1886–93.

15. Tuzun Y, Celik Y, Bayan K, Yilmaz S, Dursun M, Canoruc F.

Correlation of tumour markers in ascitic fluid and serum: are

measurements of ascitic tumour markers a futile attempt? J Int

Med Res. 2009;37(1):79–86.

16. Halperin R, Hadas E, Bukovsky I, Schneider D. Peritoneal fluid

analysis in the differentiation of ovarian cancer and benign

ovarian tumor. Eur J Gynaecol Oncol. 1999;20(1):40–4.

17. Yinnon A, Konijn AM, Link G, Moreb J, Hershko C. Diagnostic

value of ferritin in malignant pleural and peritoneal effusions.

Cancer. 1988;62(12):2564–8.

18. Tripathi PK, Chatterjee SK. Elevated expression of ferritin

H-chain mRNA in metastatic ovarian tumor. Cancer Invest.

1996;14(6):518–26.

19. Pinto V, Marinaccio M, Garofalo S, Vittoria Larocca AM, Geusa

S, Lanzilotti G, et al. Preoperative evaluation of ferritinemia in

primary epithelial ovarian cancer. Tumori. 1997;83(6):927–9.

20. Paydas S, Sargin O, Ozbek S, Gurbuz E. Ferritin levels in

malignant effusions: a useful marker?. Eur J Cancer. 1990;26(8):

919.

21. Demirkazik A, Dincol D, Hasturk S, Arican A, Karaoguz H, Cay

F, Icli F. Diagnostic value of ferritin in the differential diagnosis

of malignant effusions. Cancer Biochem Biophys. 1998;16(3):

243–51.

22. Kabawat SE, Bast RC Jr, Welch WR, Knapp RC, Bhan AK.

Expression of major histocompatibility antigens and nature of

inflammatory cellular infiltrate in ovarian neoplasms. Int J Can-

cer. 1983;32(5):547–54.

23. Rolland P, Deen S, Scott I, Durrant L, Spendlove I. Human

leukocyte antigen class I antigen expression is an independent

prognostic factor in ovarian cancer. Clin Cancer Res. 2007;

13(12):3591–6.

Med Oncol

123

Author's personal copy