PROGNOSTİC VALUE OF Kİ67 İN BORDERLİNE MUCİNOUS OVARİAN TUMORS

Year 2023, Volume: 30 Issue: 1, 123 - 129, 14.03.2023

İrfan Öcal , Sinem Demir

https://doi.org/10.17343/sdutfd.1187197

Abstract

Objective
Ovarian borderline tumors (OBTs) are an intermediate
type of ovarian neoplasm. Ovarian mucinous borderline
tumors (MBT) are the second most common subtype
of OBT. Because of their uncertain pathogenesis
and biological behaviour they cannot be classified
clearly into benign and malign categories. There is a
need to identify a parameter that provides more prog-
nostic information about the clinical course and can be
evaluated easily in routine practice. Ki67 is a routinely
used immunohistochemical marker that is strongly associated
with cellular proliferation, including tumor cells.
We aimed in this study to evaluate the prognostic
significance and to determine prognostic cut-off value
of Ki67 counting in the MBTs and to investigate its relationship
with clinicopathologic features, recurrence,
and long term survival status and also to provide more
information to the literature.
Material and Method
A total of 20 cases diagnosed with ovarian mucinous
borderline tumors were identified. Immunohistochemical
studies were performed on the most representative
sample of the tumor. Positive signal was nuclear and it
was evaluated by two pathologists.
Results
Ki67 proliferating index (P.I) value with a median of
15%(1-47%) and a mean of 16% Ki67 P.I. reached
statistically significance at 20% cut-off value with
progression and at 30% cut-off value with 5-year OS.
(p=0.021 and p=0.032, respectively). Although the
Ki67 P.I. tended to increase with age, there was no
statistical association between Kİ67 P.I. and other clinicopathological
parameters including tumor size, laterality,
capsule integrity, intraepithelial carcinoma and
focal atypia.
Conclusion
In our study, recurrence was more frequent when Ki67
was greater than 20%, and 5-year survival was lower
when Ki67 was greater than 30%, suggesting that
the Ki67 index was associated with a more aggressive
course and death. Therefore, we predicted that
Ki 67 would be useful in determining the frequency of
follow-up of patients and predicting their prognosis.
However, we think that this result should be supported
by larger series.

Keywords

Borderline, Mucinous, Ovary, Tumor, Ki67

BORDERLİNE MÜSİNÖZ OVER TÜMÖRLERİNDE Kİ67'NİN PROGNOSTİK DEĞERİ

Abstract

Amaç
Overin müsinöz borderline tümörleri (MBT), borderline
over tümörlerinin en sık görülen ikinci alt tipidir. Belirsiz
patogenezleri ve biyolojik davranışları nedeniyle, benign
veya malign kategorilere açıkça sınıflandırılamadıkları
için klinik seyir hakkında daha prognostik bilgi
sağlayan ve rutin pratikte kolaylıkla değerlendirilebilecek
bir parametrenin belirlenmesine ihtiyaç vardır.
Ki67, tümör hücreleri de dahil olmak üzere hücresel
proliferasyonla güçlü bir şekilde ilişkili olan ve rutin
olarak kullanılan bir immünohistokimyasal belirteçtir.
Bu çalışmada MBT'lerde Ki67 sayımının prognostik
önemini değerlendirmeyi ve prognostik eşik değerini
belirlemeyi ve klinikopatolojik özellikleri, nüks ve uzun
süreli sağkalım durumu ile ilişkisini araştırmayı ve ayrıca
literatüre daha fazla bilgi sağlamayı amaçladık.
Gereç ve Yöntem
Müsinöz borderline over tümörü tanısı koyulan toplam
20 vaka çalışmaya alındı. Tümörü en iyi temsil eden
örnek üzerinde immünohistokimyasal çalışmalar yapıldı.
Nükleer boyanma pozitif kabul edildi ve iki patolog
tarafından değerlendirildi
Bulgular
Ki67 proliferasyon indeksi (P.I) medyan %15 (1-47%
ve ortalama %16'dır. Ki67 P.I. progresyonla %20 eşik
değerinde ve 5 yıllık OS ile %30 eşik değerinde istatistiksel
olarak anlamlılığa ulaştı. (sırasıyla p=0.021 ve
p=0.032). Ki67 P.I. yaşla birlikte artma eğilimindeydi.
Kİ67 P.I. ile tümör boyutu, lateralite, kapsül bütünlüğü,
intraepitelyal karsinom ve fokal atipi dahil olmak üzere
diğer klinikopatolojik parametreler arasında istatistiksel
bir ilişki yoktu.
Sonuç
Çalışmamızda Ki67 %20'den yüksek olduğunda nüksün
daha sık oluşu, Ki67 %30'dan yüksek olduğunda
5 yıllık sağkalımın daha düşük oluşu Ki67 indeksinin
daha agresif seyir ve ölüm ile ilişkili olduğunu düşündürdü.
Bu nedenle Ki 67'nin hastaların takip sıklığını
belirlemede ve prognozlarını tahmin etmede faydalı
olacağını öngördük. Ancak bu sonucun daha geniş
seriler ile desteklenmesi gerektiğini düşünüyoruz.

Keywords

Borderline, Ki67, Müsinöz, Over, Tümör

References

• 1. Longacre TA, Gilks CB. Surface Epithelial Stromal Tumors of the Ovary. In: Gynecologic Pathology. 1st Ed. London: Elsevier; 2009.
• 2. Vang R, Khunamornpong S, Köbel M, Longacre TA, Ramalingam P. Who Classification of Tumours of Female Reproductive Organs. Lyon: IARC; 2020.
• 3. Hauptmann S, Friedrich K, Redline R, Avril S. Ovarian borderline tumors in the 2014 WHO classification: evolving concepts and diagnostic criteria. Virchows Arch. 2017;470(2):125–142. doi:10.1007/s00428-016-2040-8
• 4. Kurman RJ, Carcangiu ML, Harrington CS, Young RH. WHO classification of tumours of female reproductive organs. Lyon: IARC; 2014.
• 5. Rodríguez IM, Prat J. Mucinous tumors of the ovary: A clinicopathologic analysis of 75 borderline tumors (of intestinal type) and carcinomas. Am J Surg Pathol. 2002;26(2):139-52. doi:10.1097/00000478-200202000-00001
• 6. Cadron I, Leunen K, Van Gorp T, Amant F, Neven P, Vergote I. Management of borderline ovarian neoplasms. J Clin Oncol. 2007;25(20):2928-37. doi:10.1200/JCO.2007.10.8076
• 7. Tinelli R, Tinelli A, Tinelli FG, Cicinelli E, Malvasi A. Conservative surgery for borderline ovarian tumors: A review. Gynecol Oncol. 2006;100(1):185-191. doi:10.1016/j.ygyno.2005.09.021
• 8. Giurgea LN, Ungureanu C, Mihailovici MS. The immunohistochemical expression of p53 and Ki67 in ovarian epithelialborderline tumors. Correlation with clinicopathological factors. Rom J Morphol Embryol. 2012;53(4):967–973
• 9. Malpica A, Longacre TA. Prognostic indicators in ovarian serous borderline tumours. Pathology. 2018;50(2):205-213. doi: 10.1016/j.pathol.2017.12.001
• 10. Klöppel G, La Rosa S. Ki67 labeling index: assessment and prognostic role in gastroenteropancreatic neuroendocrine neoplasms. Virchows Arch. 2018;472(3):341-349. doi:10.1007/s00428-017-2258-0
• 11. Rindi G, Arnold R, Bosman F. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: WHO Classification of Tumors of the Digestive System. 4th Ed. Lyon: IARC; 2010.
• 12. Guadagno E, Pignatiello S, Borrelli G, et al. Ovarian borderline tumors, a subtype of neoplasm with controversial behavior. Role of Ki67 as a prognostic factor. Pathol Res Pract. 2019;215(11):152633. doi:10.1016/j.prp.2019.152633
• 13. Riopel MA, Ronnett BM, Kurman RJ. Evaluation of diagnostic criteria and behavior of ovarian intestinal- type mucinous tumors: Atypical proliferative (borderline) tumors and intraepithelial, microinvasive, invasive, and metastatic carcinomas. Am J Surg Pathol. 1999;23(6):617-35. doi:10.1097/00000478- 199906000-00001
• 14. Khunamornpong S, Settakorn J, Sukpan K, Suprasert P, Siriaunkgul S. Mucinous tumor of low malignant potential (“borderline” or “atypical proliferative” tumor) of the ovary: A study of 171 cases with the assessment of intraepithelial carcinoma and microinvasion. Int J Gynecol Pathol. 2011;30(3):218-30. doi:10.1097/PGP.0b013e3181fcf01a
• 15. Kim KR, Lee HI, Lee SK, Ro JY, Robboy SJ. Is stromal microinvasion in primary mucinous ovarian tumors with “mucin granuloma” true invasion? Am J Surg Pathol. 2007;31(4):546-54. doi:10.1097/01.pas.0000213430.68998.2c
• 16. Lee KR, Scully RE. Mucinous tumors of the ovary: A clinicopathologic study of 196 borderline tumors (of intestinal type) and carcinomas, including an evaluation of 11 cases with “pseudomyxoma peritonei.” Am J Surg Pathol. 2000;24(11):1447-64. doi:10.1097/00000478-200011000-00001
• 17. Garzetti GG, Ciavattini A, Goteri G, et al. Ki67 antigen immunostaining (MIB 1 monoclonal antibody) in serous ovarian tumors: Index of proliferative activity with prognostic significance. Gynecol Oncol. 1995;56(2):169-74. doi:10.1006/gyno.1995.1026
• 18. Halperin R, Zehavi S, Dar P, et al. Clinical and molecular comparison between borderline serous ovarian tumors and advanced serous papillary ovarian carcinomas. Eur J Gynaecol Oncol. 2001;22(4):292-6.
• 19. Münstedt K, Von Georgi R, Franke FE. Correlation between MIB1-determined tumor growth fraction and incidence of tumor recurrence in early ovarian carcinomas. Cancer Invest. 2004;22(2):185-94. doi:10.1081/CNV-120030206
• 20. Heeran MC, Høgdall CK, Kjaer SK, et al. Prognostic value of tissue protein expression levels of MIB-1 (Ki-67) in Danish ovarian cancer patients: From the “MALOVA” ovarian cancer study. APMIS. 2013;121(12):1177-86. doi:10.1111/apm.12071