Tumor Spreading to the Contralateral Ovary in Bilateral Ovarian Carcinoma Is a Late Event in Clonal Evolution

Tumor Spreading to the Contralateral Ovary in Bilateral Ovarian Carcinoma Is a Late Event in Clonal EvolutionTumor Menyebarkan ke kontralateral Ovarium? Di Bilateral ovarium Carcinoma Apakah Event Akhir? Di Evolution klonalIntroductionCancer 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.PendahuluanKanker 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.IntroductionThe 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.PendahuluanPertanyaan 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 MethodsThe 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 Metode70 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:as serous papillary adenocarcinoma (22 cases),endometrioid carcinoma (3 cases), adenocarcinoma NOS (one case), carcinosarcoma (one case),mucinous adenocarcinoma (one case),endometrioid and serous papillary (3 cases), andclear 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), dansel 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 alel-tumor 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.ConclusionBased 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.KesimpulanBerdasarkan 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.