TUMOR MARKER

CA 19-9

PENGGOLONGAN PENANDA TUMOR

Hormon
Enzim

Protein
Musin

onkofetal

FUNGSI MUSIN
Proteksi

tubuh dari patogen

Renewal dan diferensiasi sel
Adhesi sel dan signalling

CA 19-9

 Tahun

1978 (Koprowski) sel kanker

kolorektal manusia struktur antigen
sialyl Lewisa
Ligan untuk E-selektin kemampuan
adhesi sel kanker terhadap endotel
Antibodi monoklonal 1116-NS 19-9

 Derivat

golongan darah Lewis

Produksi Ca 19-9 memerlukan enzim
fukosiltransferase (enzim yg akan mentransfer
L-fukosa)
Sama seperti antigen Lewis yg membutuhkan
enzim fukosiltransferase untuk dapat
mengekspresikan antigen Lewis (-) 10%
orang Kaukasia
Lewis (+) kadar akan sedikit meningkat

 <<

sel epitel normal pankreas, duktus

biliaris, gaster, hepar, endometrium,
paru-paru
>>> sel epitel karsinoma pankreas,
kolon, gaster
Kadar normal : 0-37 U/L
Waktu paruh : 1-3 hari

PENINGKATAN CA 19-9
Ca pankreas (70-79%)
sensitivitas dan spesifisitas : 80-90%
+ CEA : 94%
Ca gaster (42-63%)
Ca kolorektal (18-37%)
Ca hepatoseluler (22%)
Kolestasis ekstrahepatik
Pankreatitis
Kolesistitis

JADWAL PNEGUKURAN CA 19-9

Sebelum terapi
Setelah tindakan operasi;
10 hari setelah terapi dengan interval 1-3
bulan selama 1-2 tahun pertama dan
interval 6 bulan pada tahun ke 3,4 dan 5
Diduga terjadi kekambuhan atau
metastasis

CA 19-9 As a Marker for Pancreatic Cancer

2006 recommendation for use of CA 19-9 as a screening test.
CA 19-9 is not recommended for use as a screening test for
pancreatic cancer.
2006 recommendation for use of CA 19-9 to determine operability.
The use of CA 19-9 testing alone is not recommended
for use in determining operability
or the results of operability in pancreatic cancer.
2006 recommendation for use of CA 19-9 to provide evidence of
recurrence.
CA 19-9 determinations by themselves
cannot provide definitive evidence of disease recurrence without
seeking
confirmation with imaging studies for clinical findings and/or
biopsy.

CA 19-9 As a Marker for Pancreatic Cancer

2006 recommendation for use of CA 19-9 for monitoring response to

therapy.
Present data are insufficient to recommend the routine use of
serum CA 19-9 rules alone for monitoring response to treatment.
However, CA 19-9 can be measured at the start of treatment for
locally advanced metastatic disease and every 1 to 3 months
during active treatment.
If there is an elevation in serial CA 19-9 determinations, this may be
an indication of progressive disease, and confirmation with other
studies should be sought.

14

METODE PEMERIKSAAN

RADIOIMMUNOASSAY (RIA)
Yallow dan Berson (1959)
Radioisotop sebagai penanda

16

17

ENZYME

LINKED
IMMUNOASSAY (ELISA)
Avraemas, Van Weeman dan Engvall (1971)
Aktivitas enzim
Metode Sandwich

18

ELECTROCHEMILUMINESCENT
(ECLIA)

Komponen elektrokimia pancaran cahaya

Mikropartikel berlabel streptavidin
Antibodi monoklonal berlabel biotin
Antibodi berlabel Ruthenium

19

ECL Technology
An universal principle

Streptavidin

Biotin
Antigen

Antibody
Nucleic
acid
20

21

CA 19-9

22

Terima Kasih

SENSITIVITY

The sensitivity of a test in the ability of the test to identify

correctly affected individuals
Proportion of persons testing positive among affected individuals

A ffe c te d p e rs o n s
( P o s itiv e b y g o ld s ta n d a r d )
P e r s o n s te s tin g p o s itiv e
( T r u e p o s itiv e s )

P e r s o n s te s tin g n e g a tiv e
( F a ls e n e g a tiv e s )

Sensitivity = True positives / Affected persons

Estimate the 95% confidence interval

SPECIFICITY

The specificity of a test in the ability of the test to identify

correctly non-affected individuals

Proportion of person testing negative among non affected individuals

N o n -a ffe c te d p e rs o n s
( N e g a tiv e b y g o ld s ta n d a r d )
P e r s o n s te s t in g n e g a tiv e
( T r u e n e g a tiv e s )

P e r s o n s te s tin g p o s itiv e
( F a ls e p o s itiv e s )

Specificity = True negatives / Non-affected persons

Estimate the 95% confidence interval

MUC tinggi prognosis jelek dan imunosupresi?

MUC diinkubasi dengan sel T menyebabkan anergi dari sel T
(mgkn krn MUC berinteraksi dengan reseptor sel T
Hal ini bisa dibuktikan dengan penambahan molekul MUC sintesis
MUC sintetik berkompetisi dengan MUC cancer menyebabkan
aktivasi kembali sel T
T-cell anergy induced by MUC1 is a state of unresponsiveness (not
apoptosis or death), because it can be reversed by interleukin 2 (IL2) or monoclonal antibodies against CD28.
The addition of exogenous IL-2 presumably provides the growth
factor necessary to re-activate anergic T cells, which cannot produce
sufficient endogenous IL-2 to stimulate growth. Antibodies against
CD28 provide a co-stimulatory signal that is thought to activate
transcription of endogenous IL-2
26

Peningkatan CA 19-9 pada keganasan disebabkan oleh

adanya proses nekrosis tumor, obstruksi duktus
pankreatikus sel-sel kehilangan polaritas musin
tersekresi ke dalam aliran darah

Staging

CA 19-9 value (U/ml)

IA

40.05

IIA

469.64

IIB

747.79

III

709

IV

3239

28

MUC normalnya terdapat pada apikal sel. Namun

adanya kanker menyebabkan distribusi MUC
terganggu sehingga terjadi over ekspresi MUC
dan MUC menjadi terlokalisasi di seluruh bagian
sel.
MUC juga berinteraksi dengan reseptor tirosin
kinase (RTK) signalling sel
MUC juga terakumulasi di sitoplasma sel
menyebabkan peningkatan regulasi gen yang
penting dalam pembentukan tumor, angiogenesis.
MUC pada bagian inti akan berikatan dengan
faktor transkripsi sehingga menyebabkan promosi
ekspresi gen proliferasi, survival, dan
angiogenesis
29

CA 15-3

CA 15-3

31

APLIKASI KLINIS
Monitoring progresivitas penyakit dan respon
terapi
Tidak untuk skrinning hanya meningkat pada
3% pasien dengan tumor in situ
Kadar normal tidak menyingkirkan keganasan
tergantung pada massa tumor dan akses
penanda tumor ke aliran darah

Stage I-5%, Stage II-10.6%, Stage III-29.6%, and Stage

IV-100.0%

33

CA 125

CA 125

35

CA 125

Highest CA 125 concentrations were found

during the menstruation
During the follicular and peri-ovulatory phase
CA 125 serum concentrations were lowest
Ca125 dihasilkan oleh endometrium normal
sehingga kadarnya akan meningkat dalam darah
selama menstruasi

36

premenstrual elevation of serum CA 125 : related to

premature endometrial vascular changes which are the
result of the low serum progesterone concentration
leading to insufficient endometrial control.
Sampling should not be done immediately before or
during menstruation because the physiological elevation
of the CA 125 levels may give false positive results

37

Umur kehamilan

CA 125 (U/ml)

Trimester I

51.5

Trimester II

30.8

Trimester III

56.3

38

39

Terima kasih