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

Year 2015, Volume: 12 Issue: 3, 114 - 118, 01.05.2015

Özlem Evliyaoğlu Fulya Kayıkçıoğlu Yıldırım Karslıoğlu Yusuf Aytaç Tohma Ali Haberal Ahmet Özfuttu Ömer Günhan

Abstract

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.

Keywords

Hydatidiform mole, Ki-67, image analysis

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

Abstract

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.

Keywords

Hidatidiform mol, Ki-67, görüntü analizi

References

• 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.