CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 3, April 2012
AFRICA
145
CEA.The only significant relationshipwas observedwithCA15-3
(0.027). ROC analyses were applied to detect the threshold levels
of tumour markers for detecting effusions of malignant origin.
In the ROC curve analyses, a CA 15-3 level above 25 U/ml
had a sensitivity of 71% and specificity of 78% for predicting
pericardial effusions caused by malignancies (AUC
=
0.83, SE
=
0.05,
p
=
0.002). Elevated levels of the three markers (cut-off for
CA 125
=
66 U/ml; CA 15-3
=
25 U/ml; CEA
=
4.2 U/ml) had
a sensitivity of 69% and specificity of 88% for the prediction of
pericardial effusions caused by malignancies.
In the follow-up period, levels of CA 125 and CA 15-3
decreased significantly in the patients in the idiopathic/viral
group. Levels of CA 125 also decreased significantly in the
patients in the malignancy and tuberculosis groups. However
CA 15-3 levels remained constant in the group of patients with
malignancies. Levels of CEA did not change significantly in
any group. Levels of CA 125 were significantly higher at the
beginning, but this significance decreased in the follow-up
period.
During the follow-up period, malignancy was detected in six
patients in the idiopathic group (three lymphoma, one thymoma,
one lung cancer, one gastrointestinal malignancy). CA 125 and
CA 15-3 levels were high in five and three patients, respectively.
Discussion
In this study, we examined the diagnostic value of the CA 19-9,
CA 125, CEA, CA 15-3, AFP and PSA for the diagnosis of
tumour aetiology in patients with PE. The levels of CA 15-3,
CEA and CA 125 were significantly higher in PE patients with
malignancies. In the follow-up period, the levels of CA 15-3 and
CA 125 decreased in patients in the idiopathic/viral group and
remained constant in those with malignancies. The levels of CA
15-3 were more significant in detecting malignancies than those
of CA 125.
CEA levels are known to increase in heart failure and this
marker has also been used to diagnose pleural effusions with
malignant aetiologies.
10
In many studies, a relationship has been
found between high levels of CEA and pericardial effusions
with malignant aetiologies.
5,20,21
Szturmowicz
et al
. found CEA
levels above 5 U/ml had a 90% specificity for the detection of
malignancy.
5
Similarly, in our study, the levels of CEA were
significantly higher in patients with cancer. In the follow-up
period, this significance did not change.
Lindgren
et al
. showed a relationship between CA 125 levels
and ovarian cancer.
22
More recently it was realised that CA 125
levels can also increase in benign serous effusions.
8,16,17
Unlike
CEA and CA 15-3, CA 125 is secreted from mesothelial cells in
patients with PE of benign aetiology.
7
For this reason, it can be
used to determine the existence of fluid but it does not inform
on the aetiology.
10,16,17
Two other studies revealed that CA 125
23
and CEA
24
levels
increased in heart failure, and that these levels could be related to
the amount of pericardial fluid present.
25
In our study, the levels
of these markers were significantly higher in the PE patients with
malignancies and remained high during the follow-up period.
High levels of CA 15-3 were first detected in breast cancer
patients and this was used to evaluate recurrence in the follow-
up period.
11,12
In later studies, high levels of CA 15-3 were
also found in effusion patients with malignancies.
13
Romero
et
al
. reported that CA 15-3 markers could be used to detect the
underlying aetiology of the effusion.
14
In our study, in patients with no malignancies, CA 15-3 and
CA 125 levels decreased significantly in the follow-up period.
The levels of CA 15-3 were significantly higher in patients
with malignancies and this increase remained significant in the
follow-up period. CA 15-3 was found to be a valuable marker
in the multi-analysis. In ROC curve analysis, CA 15-3 levels
above 25 U/ml had a 71% sensitivity and 55% specificity for the
prediction of malignancies underlying the pericardial effusions.
Malignancy was developed during the follow-up period in
six of our patients whose initial diagnosis was idiopathic. At
least one marker was high in five of these patients and CA 15-3
levels were high in three patients. These results indicate that if
the underlying aetiology of the PE is unknown but there are high
levels of CEA, CA 125 and CA 15-3, one should investigate for
malignancy. Use of all three markers had a low sensitivity (29%)
but a high specificity (97%) for detecting malignancy. Therefore
determination of levels of these markers is very useful in the
early diagnosis of malignancies.
Pericardiocentesis and pericardial biopsy are the best
diagnostic tests for detecting malignant aetiologies of PE.
However, where pericardiocentesis is not indicated, there are
a limited number of other tests available. This study indicates
that CA 125, CA 15-3, CEA are useful markers for detecting
malignant aetiologies of PE. High levels of all three markers
or increased levels of only CA 15-3 appeared to be predictive
of effusions caused by malignancy. High levels of CA 15-3
in the follow-up period supported our hypothesis. Effusions
categorised as idiopathic with high levels of these markers must
be followed up closely or re-examined for possible malignancies.
There were some limitations to our study. The patient
numbers in the groups according to the aetiology of PE were
not equal. The number of patients was limited and they were
heterogenous in aetiology.
Conclusion
CA 125, CA 15-3 and CEA markers can be used in the
differential diagnosis of benign and malignant aetiologies in
patients with chronic pericardial effusions. Combined use of
these three markers improves their prognostic value. Importantly,
we must suspect malignancy in patients with PE whose aetiology
cannot be determined.
References
1.
Goland S, Caspi A, Malnick SD. Idiopathic chronic pericardial effusion.
N Engl J Med
2000;
342
(19): 1449–1450.
TABLE 3. TUMOUR MARKER LEVELS OF THE
PATIENTSWITHANDWITHOUT CANCER
Malignant PE
(
n
=
27)
Non-malignant
PE
(
n
=
42)
p
CA 125 (U/ml)
90.3
±
88.6
55.2
±
67.8
0.03
CA 15-3 (U/ml)
32.3
±
14.6
17.0
±
8.9
0.002
CA 19-9 (U/ml)
18.9
±
20.2
18.7
±
19.4
NS
CEA (ng/ml)
4.5
±
5.2
2.0
±
1.2
0.04
AFP (U/ml)
1.9
±
1.7
1.7
±
0.8
NS
PSA (mg/ml)
2.1
±
2.5
3.1
±
4.1
NS
NS; not significant.
