Article Data

  • Views 2727
  • Dowloads 208

Original Research

Open Access

Cell cycle regulatory markers as potential prognostic biomarkers in uterine carcinosarcoma

  • Min-Hyun Baek1
  • Yangsoon Park2
  • Jeong-Yeol Park3,*,

1Center for Gynecologic Cancer, Research Institute and Hospital, National Cancer Center, 10408 Goyang-si, Republic of Korea

2Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 05505 Seoul, Republic of Korea

3Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, 05505 Seoul, Republic of Korea

DOI: 10.22514/ejgo.2023.034 Vol.44,Issue 3,June 2023 pp.27-34

Submitted: 28 February 2023 Accepted: 07 April 2023

Published: 15 June 2023

*Corresponding Author(s): Jeong-Yeol Park E-mail: obgyjypark@amc.seoul.kr

Abstract

The relevance of cell cycle regulatory markers with uterine carcinosarcoma was investigated. The immunohistochemical expression of p16, p53, and cyclin D1 were assessed using tissue microarray of 55 eligible patients. p16 and p53 showed a high rate of strong (+3) immune reaction in carcinomatous/sarcomatous components (61.8%/70.9% and 52.7%/56.4%, respectively). Cyclin D1 showed a 14.5%/7.3%of strong immune reaction in the carcinomatous/sarcomatous components. Strong expression of p16 was related to a higher rate of recurrence, lymph node metastasis, and bigger tumor size. Strong expression of cyclin D1 was related to the lower International Federation of Gynecology and Obstetrics (FIGO) stage and recurrence rate. In univariate regression analysis, FIGO stage, lymph node metastasis, p16, and cyclin D1 were prognostic factors for disease-free survival. FIGO stage, p16, p53, and cyclin D1 were prognostic factors for disease specific survival. In a multivariate regression analysis, FIGO stage and p16 in carcinomatous component were independent factors for disease-free survival (odds ratio (OR), 95% confidence interval (CI); 3.2 (1.1–9.6) and 3.5 (1.3–9.7); p = 0.035 and 0.017). p16 was a predictor of lymph node metastasis, tumor size, and prognostic outcome in uterine carcinosarcoma.


Keywords

Uterine neoplasm; Carcinosarcoma; p16; Cell cycle; Immunohistochemistry


Cite and Share

Min-Hyun Baek,Yangsoon Park,Jeong-Yeol Park. Cell cycle regulatory markers as potential prognostic biomarkers in uterine carcinosarcoma. European Journal of Gynaecological Oncology. 2023. 44(3);27-34.

References

[1] Cantrell LA, Blank SV, Duska LR. Uterine carcinosarcoma: a review of the literature. Gynecologic Oncology. 2015; 137: 581–588.

[2] Jung KW, Won YJ, Oh CM, Kong HJ, Cho H, Lee JK, et al. Prediction of cancer incidence and mortality in Korea, 2016. Cancer Research and Treatment. 2016; 48: 451–457.

[3] Oh C, Won Y, Jung K, Kong H, Cho H, Lee J, et al. Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2013. Cancer Research and Treatment. 2016; 48: 436–450.

[4] Berton-Rigaud D, Devouassoux-Shisheboran M, Ledermann JA, Leitao MM, Powell MA, Poveda A, et al. Gynecologic cancer intergroup (GCIG) consensus review for uterine and ovarian carcinosarcoma. International Journal of Gynecological Cancer. 2014; 24: S55–S60.

[5] McCluggage WG. Uterine carcinosarcomas (malignant mixed Mullerian tumors) are metaplastic carcinomas. International Journal of Gynecological Cancer. 2002; 12: 687–690.

[6] Abargel A, Avinoach I, Kravtsov V, Boaz M, Glezerman M, Menczer J. Expression of p27 and p53: comparative analysis of uterine carcinosarcoma and endometrial carcinoma. International Journal of Gynecological Cancer. 2004; 14: 354–359.

[7] Growdon WB, Roussel BN, Scialabba VL, Foster R, Dias-Santagata D, Iafrate AJ, et al. Tissue-specific signatures of activating PIK3CA and RAS mutations in carcinosarcomas of gynecologic origin. Gynecologic Oncology. 2011; 121: 212–217.

[8] Gillett C, Smith P, Gregory W, Richards M, Millis R, Peters G, et al. Cyclin D1 and prognosis in human breast cancer. International Journal of Cancer. 1996; 69: 92–99.

[9] Zhao P, Mao X, Talbot IC. Aberrant cytological localization of p16 and CDK4 in colorectal epithelia in the normal adenoma carcinoma sequence. World Journal of Gastroenterology. 2006; 12: 6391–6396.

[10] Coosemans A, Nik SA, Caluwaerts S, Lambin S, Verbist G, Van Bree R, et al. Upregulation of Wilms’ tumour gene 1 (WT1) in uterine sarcomas. European Journal of Cancer. 2007; 43: 1630–1637.

[11] Callister M, Ramondetta LM, Jhingran A, Burke TW, Eifel PJ. Malignant mixed Müllerian tumors of the uterus: analysis of patterns of failure, prognostic factors, and treatment outcome. International Journal of Radiation Oncology, Biology, Physics. 2004; 58: 786–796.

[12] Sharpless NE. INK4a/ARF: a multifunctional tumor suppressor locus. Mutation Research. 2005; 576: 22–38.

[13] Sellers WR, Kaelin WG Jr. Role of the retinoblastoma protein in the pathogenesis of human cancer. Role of the retinoblastoma protein in the pathogenesis of human cancer. Journal of Clinical Oncology. 1997; 15: 3301–3312.

[14] Hall M, Peters G. Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Advances in Cancer Research. 1996; 68: 67–108.

[15] D’Angelo E, Spagnoli LG, Prat J. Comparative clinicopathologic and immunohistochemical analysis of uterine sarcomas diagnosed using the World Health Organization classification system. Human Pathology. 2009; 40: 1571–1585.

[16] D’Angelo E, Prat J. Uterine sarcomas: a review. Gynecologic Oncology. 2010; 116: 131–139.

[17] Mills AM, Ly A, Balzer BL, Hendrickson MR, Kempson RL, McKenney JK, et al. Cell cycle regulatory markers in uterine atypical leiomyoma and leiomyosarcoma: immunohistochemical study of 68 cases with clinical follow-up. The American Journal of Surgical Pathology. 2013; 37: 634–642.

[18] Chen X, Arend R, Hamele-Bena D, Tergas AI, Hawver M, Tong GX, et al. Uterine carcinosarcomas: clinical, histopathologic and immunohistochemical characteristics. International Journal of Gynecological Pathology. 2017; 36: 412–419.

[19] Lynch BJ, Komaromy-Hiller G, Bronstein IB, Holden JA. Expression of DNA topoisomerase I, DNA topoisomerase II-alpha, and p53 in metastatic malignant melanoma. Human Pathology. 1998; 29: 1240–1245.

[20] Bałon B, Kaznowska E, Ignatov A, Steć A, Semczuk-Sikora A, Schneider-Stock R, et al. p53 is not related to Ki-67 immunostaining in the epithelial and mesenchymal components of female genital tract carcinosarcomas. Oncology Reports. 2013; 30: 1661–1668.

[21] Lee S, Kim HS, Kim HS, Chun YK, Hong SR, Lee J. Immunohis-tochemical study of DNA topoisomerase I, p53, and Ki-67 in uterine carcinosarcomas. Human Pathology. 2007; 38: 1226–1231.

[22] Vermij L, Léon-Castillo A, Singh N, Powell ME, Edmondson RJ, Genestie C, et al. p53 immunohistochemistry in endometrial cancer: clinical and molecular correlates in the PORTEC-3 trial. Modern Pathology. 2022; 35: 1475–1483.

[23] Nishimura Y, Watanabe J, Jobo T, Kato N, Fujisawa T, Kamata Y, et al. Cyclin D1 expression in endometrioid-type endometrial adenocarcinoma is correlated with histological grade and proliferative activity, but not with prognosis. Anticancer Research. 2004; 24: 2185–2191.

[24] Donnellan R, Chetty R. Cyclin D1 and human neoplasia. Molecular Pathology. 1998; 51: 1–7.

[25] Utsumi T, Yoshimura N, Maruta M, Takeuchi S, Ando J, Mizoguchi Y, et al. Correlation of cyclin D1 MRNA levels with clinico-pathological pa-rameters and clinical outcome in human breast carcinomas. International Journal of Cancer. 2000; 89: 39–43.

[26] Quelle DE, Ashmun RA, Shurtleff SA, Kato JY, Bar-Sagi D, Roussel MF, et al. Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes & Development. 1993; 7: 1559–1571.

[27] Bates S, Peters G. Cyclin D1 as a cellular proto-oncogene. Seminars in Cancer Biology. 1995; 6: 73–82.


Submission Turnaround Time

Top