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The Clinical Value Of Ki-67/Mib-1 Proliferation Index In Hydatidiform Mole

Yıl 2015, Cilt: 12 Sayı: 3, 114 - 118, 01.05.2015

Öz

Aim: The significance of Ki-67 index in gestational trophoblastic diseases remains a controversial issue. This study was designed to determine whether proliferation marker, Ki-67, in trophoblastic tissue would have any clinical discriminatory value.Material and Methods: The pathology reports of patients with diagnosis of complete hydatidiform mole CHM n=32 or partial hydatidiform mole PHM n=6 were included. All the patients in this study were followed up with clinical records for one year. Paraffin blocks were stained immune histochemically and computer-assisted image analysis system was used to detect Ki-67 antigen.Results: None of the continuous variables including maternal age, gravidity, size of the uterus, hemoglobin, preevacuation serum β-hCG levels were significantly correlated with Ki-67 index p>0.05 . Ki-67 index was not discriminative for symptoms and signs including vaginal bleeding, hyperemesis, asymptomatic presentation, consistency with gestational age, theca lutein cysts, hyperthyroidism, development of GTN or remission p>0.05 . On the other hand, PHMs were found to have lower Ki-67 index [median=8 IQR=11.00 ] than CHMs [median=21 IQR=43.00 ] Z=1.944; p=0.050 .Conclusion: It is our opinion that in the light of current data, it seems Ki-67 index has promising value in discriminating complete and partial HMs. Further prospective studies will help to determine the prognostic value for adverse clinical outcome.

Kaynakça

  • Saper JT. Gestational trophoblastic disease. Obstet Gynecol 2006;108:176-87.
  • Berkowitz RS, Goldstein DP. Current management of gestational trophoblastic diseases. Gynecol Oncol 2009;112:654-62.
  • Berkowitz RS, Goldstein DP. Molar pregnancy. N Engl J Med 2009; 360:1639-45.
  • Xue WC, Khoo US, Ngan HYS, et al. Minichromosome maintainance protein 7 expression in gestational trophoblastic disease: correlation with Ki67, PCNA and clinicopathological parameters. Histopathology 2003; 43:485-90.
  • Gerdes J, Schwab U, Lemke H, et al: Production of a Mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 1983; 31:13-20.
  • Miller TP, Grogan TM, Dahlberg S, et al. Prognostic significance of the Ki-67 associated proliferative antigen in agressive non-Hodgkins lymphomas: a prospective Southwest Oncology Group trial. Blood 1994; 83:1460-6.
  • Viale G, Giobbie-Hurder A, Regan MM, et al. Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol 2008; 26:5569-75.
  • Klatte T, Seligson DB, LaRochelle J, et al. Molecular signatures of localized clear cell renal cell carcinoma to predict disease-free survival after nephrectomy. Cancer Epidemiol Biomarkers Prev 2009; 18:894- 900.
  • Pence JC, Kerns BJ, Dodge RK, et al. Prognostic significance of the proliferation index in surgically resected non-small cell lung cancer. Arch Surg 1993; 128:1382-90.
  • Johannessen AL, Torp SH. The clinical value of Ki-67/MIB-1 labeling index in human astrocytomas. Pathol Oncol Res 2006; 12:143-7.
  • Lurain JR, Brewer JI, Torok EE, et al. Natural history of hydatidiform mole after primary evacuation. Am J Obstet Gyncol 1983; 145:591-5.
  • Nucci MR, Castrillon DH, Bai H, et al. Biomarkers in diagnostic obstetric and gynecologic pathology: a review. Adv Anat Pathol 2003; 10:55-68.
  • Key G, Becker MHG, Baron B, et al: New Ki-67-equivalent murine monoclonal antibodies (MIB 1-3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetitive elements encoding for the Ki-67 epitope. Lab Invest 1993; 68: 629-636.
  • Fisher RA, Newlands ES. Gestational trophoblastic disease: molecular and genetic study. J Reprod Med 1998; 43:87-97.
  • Cheung ANY, Ngan HYS, Collins RJ, et al. Assessment of cell proliferation in hydatidiform mole using monoclonal antibody MIB1 to Ki-67 antigen. J Clin Pathol 1994; 47:601-4.
  • Jeffers MD, Richmond JA, Smith R. Trophoblast proliferation rate does not predict progression to persistent gestational trophoblastic disease in complete hydatidiform mole. Int J Gynecol Pathol 1996; 15:34-8.
  • Ostrzega N, Phillipson J, Liu P. Proliferative activity in placentas with hydropic change and hydatidiform mole as detected by Ki-67 and proliferating cell nuclear antigen immunostaining. Am J Clin Pathol 1998; 110:776-81.
  • Cheville JC, Robinson R, Benda JA. Evaluation of Ki-67 (MIB-1) in placentas with hydropic change and partial and complete hydatidiform mole. Pediatr Pathol Lab Med 1996; 16:41-50.
  • Kale A, Söylemez F, Ensari A. Expressions of proliferation markers (Ki-67, proliferating cell nuclear antigen, and silver-staining nucleolar organizer regions) and of p53 tumor protein in gestational trophoblastic disease. Am J Obstet Gynecol 2001; 184:567-74.
  • Schammel DP, Bocklage T. p53, PCNA and Ki-67 in hydropic molar and nonmolar placentas: an immunohistochemical study. Int J Gynecol Pathol 1996; 15:158-66.

Ki-67/Mib-1 Proliferasyon İndeksinin Hidatiform Mol Tanısındaki Klinik Değeri

Yıl 2015, Cilt: 12 Sayı: 3, 114 - 118, 01.05.2015

Öz

Amaç: Gestasyonel trofoblastik hastalıklarda Ki-67 indeksinin önemi hala tartışılan bir konudur. Bu çalışmanın amacı proliferasyon markerlarından olan Ki-67’nin trofoblastik hastalıklarda ayırıcı tanıda herhangi bir değerinin olup olmadığını belirlemektir.Gereç ve Yöntemler: Çalışmaya, komplet hidatidiform mol tanısı almış n = 32 veya parsiyel mol tanısı almış n = 6 hastaların patoloji raporları dahil edildi. Çalışmaya dahil edilen tüm hastaların kliniği 1 yıl boyunca izlendi. Parafin bloklar immünhistokimyasal olarak boyandı ve bilgisayarla asiste görüntü analiz sistemi ile Ki-67 antijeni açısından incelendi.Bulgular: Maternal yaş, gravida, uterus büyüklüğü, hemoglobin, serum β-hCG seviyesi gibi devamlı değişkenlerin hiçbiri Ki-67 indeksi ile anlamlı korele değildi p>0.05 . Ki-67 indeksi, vajinal kanama, hiperemezis, asemptomatik prezentasyon, gebelik yaşı ile tutarlılık, teka lutein kisti, hipertiroidizm, GTN gelişimi ya da remisyonu gibi semptom ve şikayetlerle korele değildi. Fakat parsiyel molde Ki-67 indeksi [median=8 IQR=11.00 ] , komplet mole göre [median=21 IQR=43.00 ] daha düşük bulundu Z=1.944; p=0.050 .Sonuç: Bizim çalışmamızdaki datalar, Ki-67 indeksinin komplet mol ile parsiyel mol ayırımında umut verici bir marker olduğunu göstermektedir. Bizim bulgularımızın prospektif çalışmalarla desteklenmesi gerekmektedir.

Kaynakça

  • Saper JT. Gestational trophoblastic disease. Obstet Gynecol 2006;108:176-87.
  • Berkowitz RS, Goldstein DP. Current management of gestational trophoblastic diseases. Gynecol Oncol 2009;112:654-62.
  • Berkowitz RS, Goldstein DP. Molar pregnancy. N Engl J Med 2009; 360:1639-45.
  • Xue WC, Khoo US, Ngan HYS, et al. Minichromosome maintainance protein 7 expression in gestational trophoblastic disease: correlation with Ki67, PCNA and clinicopathological parameters. Histopathology 2003; 43:485-90.
  • Gerdes J, Schwab U, Lemke H, et al: Production of a Mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 1983; 31:13-20.
  • Miller TP, Grogan TM, Dahlberg S, et al. Prognostic significance of the Ki-67 associated proliferative antigen in agressive non-Hodgkins lymphomas: a prospective Southwest Oncology Group trial. Blood 1994; 83:1460-6.
  • Viale G, Giobbie-Hurder A, Regan MM, et al. Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole. J Clin Oncol 2008; 26:5569-75.
  • Klatte T, Seligson DB, LaRochelle J, et al. Molecular signatures of localized clear cell renal cell carcinoma to predict disease-free survival after nephrectomy. Cancer Epidemiol Biomarkers Prev 2009; 18:894- 900.
  • Pence JC, Kerns BJ, Dodge RK, et al. Prognostic significance of the proliferation index in surgically resected non-small cell lung cancer. Arch Surg 1993; 128:1382-90.
  • Johannessen AL, Torp SH. The clinical value of Ki-67/MIB-1 labeling index in human astrocytomas. Pathol Oncol Res 2006; 12:143-7.
  • Lurain JR, Brewer JI, Torok EE, et al. Natural history of hydatidiform mole after primary evacuation. Am J Obstet Gyncol 1983; 145:591-5.
  • Nucci MR, Castrillon DH, Bai H, et al. Biomarkers in diagnostic obstetric and gynecologic pathology: a review. Adv Anat Pathol 2003; 10:55-68.
  • Key G, Becker MHG, Baron B, et al: New Ki-67-equivalent murine monoclonal antibodies (MIB 1-3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetitive elements encoding for the Ki-67 epitope. Lab Invest 1993; 68: 629-636.
  • Fisher RA, Newlands ES. Gestational trophoblastic disease: molecular and genetic study. J Reprod Med 1998; 43:87-97.
  • Cheung ANY, Ngan HYS, Collins RJ, et al. Assessment of cell proliferation in hydatidiform mole using monoclonal antibody MIB1 to Ki-67 antigen. J Clin Pathol 1994; 47:601-4.
  • Jeffers MD, Richmond JA, Smith R. Trophoblast proliferation rate does not predict progression to persistent gestational trophoblastic disease in complete hydatidiform mole. Int J Gynecol Pathol 1996; 15:34-8.
  • Ostrzega N, Phillipson J, Liu P. Proliferative activity in placentas with hydropic change and hydatidiform mole as detected by Ki-67 and proliferating cell nuclear antigen immunostaining. Am J Clin Pathol 1998; 110:776-81.
  • Cheville JC, Robinson R, Benda JA. Evaluation of Ki-67 (MIB-1) in placentas with hydropic change and partial and complete hydatidiform mole. Pediatr Pathol Lab Med 1996; 16:41-50.
  • Kale A, Söylemez F, Ensari A. Expressions of proliferation markers (Ki-67, proliferating cell nuclear antigen, and silver-staining nucleolar organizer regions) and of p53 tumor protein in gestational trophoblastic disease. Am J Obstet Gynecol 2001; 184:567-74.
  • Schammel DP, Bocklage T. p53, PCNA and Ki-67 in hydropic molar and nonmolar placentas: an immunohistochemical study. Int J Gynecol Pathol 1996; 15:158-66.
Toplam 20 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Research Article
Yazarlar

Özlem Evliyaoğlu Bu kişi benim

Fulya Kayıkçıoğlu Bu kişi benim

Yıldırım Karslıoğlu Bu kişi benim

Yusuf Aytaç Tohma Bu kişi benim

Ali Haberal Bu kişi benim

Ahmet Özfuttu Bu kişi benim

Ömer Günhan Bu kişi benim

Yayımlanma Tarihi 1 Mayıs 2015
Yayımlandığı Sayı Yıl 2015 Cilt: 12 Sayı: 3

Kaynak Göster

Vancouver Evliyaoğlu Ö, Kayıkçıoğlu F, Karslıoğlu Y, Tohma YA, Haberal A, Özfuttu A, Günhan Ö. Ki-67/Mib-1 Proliferasyon İndeksinin Hidatiform Mol Tanısındaki Klinik Değeri. JGON. 2015;12(3):114-8.