Obstet Gynecol Sci.  2020 Jul;63(4):464-469. 10.5468/ogs.19204.

Prognostic impact of p16 and p53 gene expressions in stage 1a epithelial ovarian cancer

• Günakan E
• Tohma YA
• Karakaş LA
• Akıllı H
• Haberal AN
• Ayhan A

• KMID: 2505036
• DOI: http://doi.org/10.5468/ogs.19204

Abstract

Objective
Epithelial ovarian cancer (EOC) is rarely detected at stage 1a. Most of the patients have a good prognosis and there are limited factors that affect their survival. In the present study, we evaluated the p16 and p53 gene expressions of stage 1a EOC patients. Prognostic effects of these gene expressions, as well as those of other factors on short term survival were analyzed.
Methods
Our study included 29 patients. The specimens of the ovary with cancer were stained for p16 and p53. Gene expressions and other prognostic factors were evaluated.
Results
The median age of the patients was 51 years (27–84). The mean numbers of dissected pelvic and paraaortic lymph nodes were 27 and 12, respectively. The mean follow-up time was 33.7±18.9 months. During this period, recurrence occurred in two patients. One of the patients had grade 2 mucinous carcinoma and died of the disease at month 12 after the recurrence occurred at month 7. The second patient had clear cell carcinoma and recurrence occurred at month 34. p16 and p53 gene expressions or other factors were not associated with overall survival (OS) or disease-free survival in the short term. The lower p16 positivity rate in the non-clear cell group was found to be statistically significant (P=0.003). Both p53 and p16 positivity rates were higher in the high-grade carcinoma.
Conclusion
The levels of none of the common prognostic factors, including those of p16 and p53 gene expression, were associated with the progression-free survival or OS of stage 1a in the short term. Appropriate surgical staging and non-omission of subclinical metastases seem to be of central importance.

Keyword

Disease-free survival; Genes, p16; Genes, p53; Progression-free survival

Figure

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  Fig. 1. (A) Weak staining pattern with p16 marker (×10 high-power field [HPF]); (B) Moderate staining pattern with p16 marker (×20 HPF); (C) Strong staining pattern with p16 marker (×10 HPF).

Reference

References

1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136:E359–86.

2. Chan JK, Tian C, Monk BJ, Herzog T, Kapp TS, Bell J, et al. Prognostic factors for high-risk early-stage epithelial ovarian cancer. Cancer. 2008; 112:2202–10.

3. Ayhan A, Reed N, Gultekin M, Dursun P. Early stage epithelial ovarian cancer. In : Ayhan A, Reed N, Gultekin M, Dursun P, editors. Textbook of gynaecolgical oncology. 2nd ed. Ankara: Güneş Tıp Kitapevleri;2011. p. 429–31.

4. Vousden KH, Lane DP. p53 in health and disease. Nat Rev Mol Cell Biol. 2007; 8:275–83.

5. Ayhan A, Reed N, Gultekin M, Dursun P. prognostic factors for gynecologic cancers. In : Ayhan A, Reed N, Gultekin M, Dursun P, editors. Textbook of gynaecolgical oncology. 2nd ed. Ankara: Güneş Tıp Kitapevleri;2011. p. 1056–60.

6. McMenamin ME, O’Neill AJ, Gaffney EF. Extent of apoptosis in ovarian serous carcinoma: relation to mitotic and proliferative indices, p53 expression, and survival. Mol Pathol. 1997; 50:242–6.

7. Singer G, Kurman RJ, Chang HW, Cho SK, Shih IM. Diverse tumorigenic pathways in ovarian serous carcinoma. Am J Pathol. 2002; 160:1223–8.

8. Katsaros D, Cho W, Singal R, Fracchioli S, Rigault De La Longrais IA, Arisio R, et al. Methylation of tumor suppressor gene p16 and prognosis of epithelial ovarian cancer. Gynecol Oncol. 2004; 94:685–92.

9. Rodriguez M, Nguyen HN, Averette HE, Steren AJ, Penalver MA, Harrison T, et al. National survey of ovarian carcinoma XII. Epithelial ovarian malignancies in women less than or equal to 25 years of age. Cancer. 1994; 73:1245–50.

10. Schildkraut JM, Halabi S, Bastos E, Marchbanks PA, McDonald JA, Berchuck A. Prognostic factors in early-onset epithelial ovarian cancer: a population-based study. Obstet Gynecol. 2000; 95:119–27.

11. Zanetta G, Rota S, Chiari S, Bonazzi C, Bratina G, Torri V, et al. The accuracy of staging: an important prognostic determinator in stage I ovarian carcinoma. A multivariate analysis. Ann Oncol. 1998; 9:1097–101.

12. Ayhan A, Celik H, Taskiran C, Bozdag G, Aksu T. Oncologic and reproductive outcome after fertility-saving surgery in ovarian cancer. Eur J Gynaecol Oncol. 2003; 24:223–32.

13. Colombo N, Chiari S, Maggioni A, Bocciolone L, Torri V, Mangioni C. Controversial issues in the management of early epithelial ovarian cancer: conservative surgery and role of adjuvant therapy. Gynecol Oncol. 1994; 55:S47–51.

14. Mutch DG. Ovarian and tubal cancers. In : Gibbs RS, Karlan BY, Haney AF, Nygaard IE, editors. Danforth’s obstetrics and gynecology. 10th ed. Philadelphia (PA): Lippincott Williams & Wilkins;2008. p. 1023–60.

15. Le T, Adolph A, Krepart GV, Lotocki R, Heywood MS. The benefits of comprehensive surgical staging in the management of early-stage epithelial ovarian carcinoma. Gynecol Oncol. 2002; 85:351–5.

16. Chan J, Fuh K, Shin J, Cheung M, Powell C, Chen LM, et al. The treatment and outcomes of early-stage epithelial ovarian cancer: have we made any progress? Br J Cancer. 2008; 98:1191–6.

17. Seidman JD, Kurman RJ. Pathology of ovarian carcinoma. Hematol Oncol Clin North Am. 2003; 17:909–25.

18. Ellenson LH, Pirog EC. The female genital tract. In : Kumar V, Abbas AK, Fausto N, editors. Robbins and Cotran pathologic basis of disease. 7th ed. Philadelphia (PA): Elsevier Saunders;2005. p. 1092–104.

19. Kurman RJ, Shih IM. Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. Int J Gynecol Pathol. 2008; 27:151–60.

20. Darcy KM, Brady WE, McBroom JW, Bell JG, Young RC, McGuire WP, et al. Associations between p53 overexpression and multiple measures of clinical outcome in high-risk, early stage or suboptimally-resected, advanced stage epithelial ovarian cancers A Gynecologic Oncology Group study. Gynecol Oncol. 2008; 111:487–95.

21. Skírnisdóttir IA, Sorbe B, Lindborg K, Seidal T. Prognostic impact of p53, p27, and C-MYC on clinicopathological features and outcome in early-stage (FIGO I-II) epithelial ovarian cancer. Int J Gynecol Cancer. 2011; 21:236–44.

22. Skírnisdóttir I, Seidal T. Prognostic impact of concomitant p53 and PTEN on outcome in early stage (FIGO I-II) epithelial ovarian cancer. Int J Gynecol Cancer. 2011; 21:1024–31.

23. de Graeff P, Crijns AP, de Jong S, Boezen M, Post WJ, de Vries EG, et al. Modest effect of p53, EGFR and HER-2/neu on prognosis in epithelial ovarian cancer: a meta-analysis. Br J Cancer. 2009; 101:149–59.

24. García-Velasco A, Mendiola C, Sánchez-Muñoz A, Ballestín C, Colomer R, Cortés-Funes H. Prognostic value of hormonal receptors, p53, ki67 and HER2/neu expression in epithelial ovarian carcinoma. Clin Transl Oncol. 2008; 10:367–71.

25. Lee YK, Park NH. Prognostic value and clinicopathological significance of p53 and PTEN in epithelial ovarian cancers. Gynecol Oncol. 2009; 112:475–80.

26. Khouja MH, Baekelandt M, Nesland JM, Holm R. The clinical importance of Ki-67, p16, p14, and p57 expression in patients with advanced ovarian carcinoma. Int J Gynecol Pathol. 2007; 26:418–25.

27. Surowiak P, Materna V, Maciejczyk A, Pudelko M, Suchocki S, Kedzia W, et al. Decreased expression of p16 in ovarian cancers represents an unfavourable prognostic factor. Histol Histopathol. 2008; 23:531–8.