Tumor Spreading to the Contralateral

Ovary
in Bilateral Ovarian Carcinoma Is a
Late Event
in Clonal Evolution
Tumor Menyebarkan ke
kontralateral Ovarium? Di Bilateral
ovarium Carcinoma Apakah Event
Akhir? Di Evolution klonal

Introduction
Cancer of the ovary represents 30%
of all malignancies of the female
genital organs.
Bilateral carcinomas of the ovary
vary in frequency depending on
which tumor type is involved but can
be found in roughly 25% of all
ovarian cancer cases.

Pendahuluan
Kanker ovarium merupakan 30% dari
seluruh keganasan dari organ genital
perempuan.
Karsinoma
bilateral
ovarium
bervariasi
dalam
frekuensi
tergantung pada jenis tumor yang
terlibat tetapi dapat ditemukan di
sekitar 25% dari semua kasus kanker
ovarium.

Introduction
The question of whether bilateral
ovarian carcinomas are the result of
metastatic spreading from one ovary
harboring the primary tumor to the
contralateral ovary, as opposed to the
alternative, simultaneous occurrence
of two independent primary tumors,
was addressed nearly two decades
ago by Pejovic et al.

Pendahuluan
Pertanyaan
apakah
karsinoma
ovarium bilateral adalah hasil dari
metastasis menyebar dari satu
ovarium menyembunyikan tumor
primer ke ovarium kontralateral,
sebagai lawan alternatif, terjadinya
simultan dari dua tumor primer
independen, ditujukan hampir dua
dekade lalu oleh Pejovic et al.

Material and Methods

The 70 tumors came from altogether
32 patients with bilateral ovarian
cancer. From all patients we had
tumor material from both ovaries,
and fromsix patients we also had
samples from a metastasis to the
omentum
(three
patients)
or
peritoneal cavity (three patients).

Bahan dan Metode

70 tumor berasal dari sama sekali 32
pasien dengan kanker ovarium
bilateral. Dari semua pasien kami
memiliki bahan tumor dari kedua
ovarium, dan pasien fromsix kami
juga memiliki sampel dari metastasis
ke omentum (tiga pasien) atau
rongga peritoneum (tiga pasien).

The tumors were classified:

1. as serous papillary adenocarcinoma (22 cases),
2. endometrioid carcinoma (3 cases),
3. adenocarcinoma NOS (one case),
4. carcinosarcoma (one case),
5. mucinous adenocarcinoma (one case),
6. endometrioid and serous papillary (3 cases),
and
7. clear cell and serous papillary carcinoma (one
case).

Tumor diklasifikasikan:
adenokarsinoma papiler sebagai serosa (22
kasus),
Karsinoma endometrioid (3 kasus),
adenokarsinoma NOS (satu kasus),
carcinosarcoma (satu kasus),
adenokarsinoma mucinous (satu kasus),
endometrioid dan papiler serosa (3 kasus), dan
sel jernih dan karsinoma papiler serosa (satu
kasus).

 As ovarian cancer can be part of the

hereditary nonpolyposis colon cancer
(HNPCC) spectrum, characterized by
microsatellite instability (MSI);

 Seperti
kanker
ovarium
dapat
menjadi bagian dari kanker usus
besar
nonpolyposis
herediter
(HNPCC) spektrum, ditandai dengan
ketidakstabilan mikrosatelit (MSI);

 A tumor was considered to be MSI-high if two or more

of the five markers exhibited novel alleles compared to
normal DNA, MSI-low if only one marker deviated from
the normal pattern, and microsatellite stable (MSS) if
none of the tumor genotypes showed an aberrant
pattern. Control DNA corresponding to the individual
tumors was not available from the patients and
therefore single allele changes, that is, the presence of
two different alleles, can reflect a heterozygous
constitutional genotype or a homozygous genotype
with a novel tumor-specific allele. Thus, dinucleotide
markers were anot scored when such a pattern
appeared in the tumors.

 Tumor dianggap MSI tinggi jika dua atau lebih dari lima
penanda dipamerkan alel baru dibandingkan dengan
DNA normal, MSI-rendah jika hanya satu penanda
menyimpang dari pola normal, dan mikrosatelit stabil
(MSS) jika tidak ada genotipe tumor menunjukkan pola
yang menyimpang. Kontrol DNA sesuai dengan tumor
individu tidak tersedia dari pasien dan perubahan alel
karena tunggal, yang, kehadiran dua alel yang
berbeda, dapat mencerminkan genotipe heterozigot
konstitusional atau genotipe homozigot dengan aleltumor tertentu baru. Dengan demikian, penanda
dinukleotida tidak mencetak gol ketika pola seperti
muncul di tumor.

Discussion (Kariotype)
Cytogenetic studies of bilateral ovarian cancer are
limited to the one by Pejovic et al. [3] who
karyotyped tumors from both ovaries in 15
patients. Because the baselin karyotypes in each
tumor pair were identical in the 11 patients from
whom informative results were obtained, the
conclusion was that the second tumor always
arose by spreading of a monoclonal process from
the first one. However, since the clonal evolution
of the neoplastic cells in the two locations was
similar, one could not determine which tumor was
primary and which was metastatic.

Diskusi (kariotipe)
Studi sitogenetika kanker ovarium bilateral
terbatas pada satu per Pejovic et al. [3] yang
kariotipe tumor dari kedua ovarium pada 15
pasien. Karena kariotipe dasar di masing-masing
pasangan tumor identik dalam 11 pasien dari
siapa hasil informatif diperoleh, kesimpulannya
adalah bahwa tumor kedua selalu timbul oleh
penyebaran proses monoklonal dari yang
pertama. Namun, karena evolusi klonal sel-sel
neoplastik di dua lokasi serupa, salah satu tidak
bisa menentukan tumor primer dan yang
metastasis.

Discussion (HR-CGH)
Regardless of what it might mean,
the direct pathogenetic significance
of
this
specific
gain
remains
unknown;
possibly
oncogene(s)
located in 5p14 may be active in
ovarian carcinogenesis and/or tumor
progression and spreading.

Diskusi (HR-CGH)
Terlepas dari apa yang mungkin
berarti, signifikansi patogen langsung
keuntungan tertentu masih belum
diketahui; mungkin onkogen (s)
terletak di 5p14 mungkin aktif di
karsinogenesis ovarium dan / atau
perkembangan tumor dan menyebar.

Discussion (MSI)
DNA microsatellite instability reflects an altered
pattern
of
short
tandem
repeat
sequences
(microsatellites) in dividing cells and has been
described in HNPCC as well as other tumor types.
Ovarian cancer, although most often sporadic, can
occur together with HNPCC as part of the Lynch cancer
family syndrome [47]. Several studies have suggested
an association between MSI and certain histological
types of ovarian carcinoma. However, in most of these
studies, different kinds of microsatellite markers were
used, and the presence of MSI was declared based on
the demonstration of instability at only one locus.

Diskusi (MSI)
Ketidakstabilan mikrosatelit DNA mencerminkan pola
yang berubah urutan tandem repeat singkat
(mikrosatelit) dalam sel membagi dan telah dijelaskan
dalam HNPCC serta jenis tumor lainnya. Kanker
ovarium, meskipun paling sering sporadis, dapat terjadi
bersama-sama dengan HNPCC sebagai bagian dari
sindrom Lynch keluarga kanker [47]. Beberapa studi
telah menunjukkan hubungan antara MSI dan jenis
histologis tertentu karsinoma ovarium. Namun, di
sebagian besar penelitian ini, berbagai jenis penanda
mikrosatelit yang digunakan, dan kehadiran MSI
dinyatakan berdasarkan demonstrasi ketidakstabilan
hanya pada satu lokus.

Conclusion
Based on baseline kariotype, bilateral ovarian
cancer occurs via a metastatic mechanism,
but the addition of CGH data allowed us to
expand
on
this
assessment
of
the
pathogenetic
connection
between
macroscopically discrete tumor lesions: the
fact that so many aberrations are common to
the tumors in both sides indicates that
spreading to the contralateral ovary is a late
event in the clonal evolution of the neoplastic
parenchyma cells.

Kesimpulan
Berdasarkan kariotipe dasar, kanker ovarium
bilateral
terjadi
melalui
mekanisme
metastasis, tapi penambahan data CGH
memungkinkan kami untuk memperluas
penilaian ini koneksi patogen antara lesi
tumor mikroskopis diskrit: fakta bahwa begitu
banyak penyimpangan yang umum untuk
tumor di kedua sisi menunjukkan bahwa
menyebar ke ovarium kontralateral adalah
acara akhir dalam evolusi klonal sel parenkim
neoplastik.