Hubungan antara Ekspresi P53 Mutan terhadap Operabilitas Kanker Serviks Stadium IIB Pasca Kemoterapi Neoajuvan

https://doi.org/10.22146/jkr.53838

Nur Rohmah Arsyad(1*), Risanto Siswosudarmo(2), Ardhanu Kusumanto(3)

(1) Departemen Obstetri dan Ginekologi, FK-KMK, UGM
(2) Departemen Obstetri dan Ginekologi, FK-KMK, UGM
(3) Departemen Obstetri dan Ginekologi, FK-KMK, UGM
(*) Corresponding Author

Abstract


Background: The therapy for stage IIB cervical cancer according to FIGO is concurrent chemoradiation. The neoadjuvant chemotherapy followed by radical hysterectomy is an alternative therapy to improve the survival rate of cancer patients. Cervical cancer is mainly caused by the infection of Human Papilloma Virus (HPV), which contains protein E6 and E7 that downregulate the apoptotic function of p53. The absent of p53 wild-type and the present of p53 mutation play roles on the cervical cancer pathogenesis.

Objective: To analyze the association between the expression of mutant p53 to the stage IIB cervical cancer operability after neoadjuvant chemotherapy

Method: This study was a prospective cohort, using 40 of 67 patient who met eligibility criteria. The parafin block from cervical tissue were processed for immunohistochemical staining of p53 using Anti-mutant p53 antibody [Y5] ab32049, Abcam, USA. Two study groups were assessed as: 1) weak and 2) strong expression of mutant p53 expression after neoadjuvant chemotherapy based on H-score. Both group (weak and strong) were comparable in term of mutant p53 expression. In this study, the evaluation of operability was performed clinically. Age, BMI, histopathology, grade of differentiation, and regiment were also evaluated as the external variables. Chi square test, and logistic regression analysis were used for statistical analysis.

Results and Discussion: The rate of cervical cancer operability after chemotherapy was 19 out of 40 (47.5%). The strong expression of mutant p53 was observed in 6 subjects (15%). There was no significant association between weak vs strong expression of mutant p53 to the operability of the cancer (RR 1.5, CI 95% 0.46-4.88, p 0.45). Multivariate analysis showed that combination (50 mg/m2 dan 5 fluorourasil 450 mg/m2) was significantly correlated the operability (OR 7.02, CI 95% 1.27-40.07,  p 0.03). 

Conclusion: The expression of mutant p53 not correlate with operability after neoadjuvant chemotherapy, but combination  regiment was.

Keywords: expression of mutant p53, stage IIB of cervical cancer, neoadjuvant chemotherapy, operability


Keywords


expression of mutant p53; stage IIB of cervical cancer; neoadjuvant chemotherapy; operability

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References

Liu L, Li XD, Chen HY, Cui JS, Xu DY. Significance of Ebp1 and p53 protein Expression in Cervical Cancer. Genet Mol Res. 2015;14(4):11860–6.

Di Saia PJ, Creasman WJ. Clinical Gynecologic Oncology. Eight Edit. Philadelphia: Elsevier Saunders; 2012.

Karlan BY, Brostow RE, Li AJ. Gynecologic Oncology Clinical Practice & Surgical Atlas. Journal of Chemical Information and Modeling. McGraw-Hill Company; 2013. 1689-1699 p.

Badan Penelitian dan Pengembangan Kesehatan Kementerian Kesehatan. Riset Kesehatan Dasar (RISKESDAS) 2013. 2013;

Kementrian Kesehatan RI Pusat Data dan Informasi Kesehatan. Situasi Penyakit Kanker. infodatin-Stop Kanker. 2015;hal 3.

Saha SK, Khuda-Bukhsh AR. Berberine alters Epigenetic Modifications, Disrupts Microtubule Network, and Modulates HPV-18 E6-E7 Oncoproteins by Targeting p53 in Cervical Cancer cell HeLa: A Mechanistic Study Including Molecular Docking. Eur J Pharmacol

World Health Organization. Comprehensive Cervical Cancer Control A Guide to Essential Practice [Internet]. WHO Library Cataloguing-in-Publication Data. 2014.

Ikuta A, Saito J, Mizokami T, Nakamoto T, Yasuhara M, Nagata F, et al. Correlation p53 Expression and Muman Papilloma Virus Deoxyribonucleic Acid with Clinical Outcome in Early Uterine Cervical Carcinoma. Cancer Detect Prev. 2005;29(6):528–36.

Habbous S, Pang V, Eng L, Xu W, Kurtz G, Liu FF, et al. p53 Arg72Pro Polymorphism, HPV Status and Initiation, Progression, and Development of Cervical Cancer: A Systematic Review and Metaanalysis. Clin Cancer Res. 2012;18(23):6407–15.

Sandhu JK, Shivakumar S. Study of p53 in Cervical Intraepithelial Neoplasia and Carcinoma Cervix with Clinico-pathological Correlation. Int J Sci Study. 2016;4(1):208–14.

Thakrar M, Mathur K. Immunohistochemical Study of p53 Expression as Proliferative Index in Neoplasia of the Uterine Cervix. Int Arch Integr Med [Internet]. 2017;4(12):16–25. Available from: http://iaimjournal.com

Oh MJ, Choi JH, Lee YH, Lee JK, Hur JY, Park YK, et al. Mutant p53 Protein in the Serum of Patients with Cervical Carcinoma: Correlation with the Level of Serum Epidermal Growth Factor Receptor and Prognostic Significance. Cancer Lett [Internet]. 2004;203(1):107–12.

Zhou R, Wei C, Liu J, Luo Y, Tang W. The Prognostic Value of p53 Expression for Patients with Cervical Cancer: A Meta Analysis. Eur J Obstet Gynecol Reprod Biol [Internet]. Elsevier Ireland Ltd; 2015;195:210–3.

Wiebe E, Denny L, Thomas G. FIGO Cancer Report 2012 Cancer of the Cervix Uteri. Int J Gynecol Obs. 2012;2:100–9.

Tierney J., Neoadjuvant Chemotherapy for Cervical Cancer Meta-analysis Collaboration (NACCMA) Collaboration, L R. Neoadjuvant Chemotherapy for Locally Advanced Cervix Cancer ( Review ). Cochrane Collab [Internet]. 2015;(2):1–42.

Robova H, Rob L, Halaska MJ, Pluta M, Skapa P, Strnad P, et al. High-Dose Density Neoadjuvant Chemotherapy in Bulky IB Cervical Cancer. Gynecol Oncol [Internet]. Elsevier Inc.; 2013;128(1):49–53

Rydzewska L, Tierney J, Vale CL, Symonds PR. Neoadjuvant Chemotherapy Plus Surgery Versus Surgery for Cervical Cancer. Cochrane database Syst Rev [Internet]. 2012;12(12):CD007406.

Prakosa T, Askandar B, Fauziah D. Ekspresi p53 Mutan dan Caspase 3 sebagai Faktor Prediksi terhadap Operabilitas Kanker Serviks IIB setelah Mendapat Kemoterapi Neoadjuvan. Indones J Cancer. 2013;7(2):61–7.

Kasamatsu T, Onda T, Sawada M, Kato T, Ikeda S. Radical Hysterectomy for FIGO stage IIB Cervical Cancer : Clinicopathological Characteristics and Prognostic Evaluation. Gynecol Oncol [Internet]. Elsevier Inc.; 2009;114(1):69–74.

Robova H, Halaska MJ, Pluta M, Skapa P, Matecha J, Lisy J, et al. Oncological and Pregnancy Outcomes after High-Dose Density Neoadjuvant Chemotherapy and Fertility-Sparing Surgery in Cervical cancer. Gynecol Oncol [Internet]. Elsevier Inc.; 2014;135(2):213–6

Chen M-B, Zhu Y-Q, Xu J-Y, Wang L-Q, Liu C-Y, Ji Z-Y, et al. Value of TP53 Status for Predicting Response to Neoadjuvant Chemotherapy in Breast Cancer: a meta-analysis. PLoS One [Internet]. 2012;7(6):e39655–e39655.

Kim HS, Sardi JE, Katsumata N, Ryu HS, Nam JH, Chung HH, et al. Efficacy of Neoadjuvant Chemotherapy in Patients with FIGO Stage IB1 to IIA Cervical Cancer: An International Collaborative Metaanalysis. Eur J Surg Oncol [Internet]. Elsevier Ltd; 2013;39(2):115–24

Qin T, Zhen J, Zhou M, Wu H, Ren R, Qu B, et al. Efficacy of Neoadjuvant Chemotherapy Plus Radical Surgery in Patients with Bulky Stage II Cervical Squamous Cell Carcinoma: A Retrospective Cohort Study. Int J Surg [Internet]. 2016;30:121–5.

Scandurra G, Scibilia G, Banna GL, D???Agate G, Lipari H, Gieri S, et al. Efficacy and tolerability of paclitaxel, ifosfamide, and cisplatin as a neoadjuvant chemotherapy in locally advanced cervical carcinoma. J Gynecol Oncol. 2015;26(2):118–24.

Katsumata N, Yoshikawa H, Kobayashi H, Saito T, Kuzuya K, Nakanishi T, et al. Phase III Randomised Controlled Trial of Neoadjuvant Chemotherapy plus Radical Surgery vs Radical Surgery alone for Stages IB2 , IIA2 , and IIB Cervical Cancer : a Japan Clinical Oncology Group Trial ( JCOG 0102 ). Br J Cancer [Internet]. Nature Publishing Group; 2013;108(10):1957–63.

Yang Z, Chen D, Zhang J, Yao D, Gao K, Wang H, et al. The Efficacy and Safety of Neoadjuvant Chemotherapy in The Treatment of Locally Advanced Cervical Cancer: A Randomized Multicenter Study. Gynecol Oncol. 2015;141:231–9.

Hu T, Li S, Chen Y, Shen J, Li X, Huang K, et al. Matched-case Comparison of Neoadjuvant Chemotherapy in Patients with FIGO Stage IB1-IIB Cervical Cancer to Establish Selection Criteria. Eur J Cancer. 2012;48:2353–60.

Chen H, Liang C, Zhang L, Huang S, Wu X. Clinical Efficacy of Modified Preoperative Neoadjuvant Chemotherapy in the Treatment of Locally Advanced (Stage IB2 to IIB) Cervical Cancer: Randomized Study. Gynecol Oncol [Internet]. Elsevier Inc.; 2008;110(3):308–15.

Angioli R, Plotti F, Montera R, Aloisi A, Luvero D, Capriglione S, et al. Neoadjuvant Chemotherapy plus Radical Surgery Followed by Chemotherapy in Locally Advanced Cervical Cancer. Gynecol Oncol [Internet]. Elsevier Inc.; 2012;127(2):290–6.



DOI: https://doi.org/10.22146/jkr.53838

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