Title
Author
DOI
Article Type
Special Issue
Volume
Issue
Effectiveness of human epididymis protein 4 (HE4) as predictor of response to first line platinum based chemotherapy
1Department of Obstetrics and Gynecology, University of Rome ‘‘Campus Bio-Medico’’, Via Alvaro del Portillo, 200-00128 Rome, Italy
2Department of Gynecology, Obstetrics and Urology, Policlinico Umberto I, ‘‘Sapienza’’ University of Rome, 00186 Rome, Italy
3Unit of Medical Statistics and Molecular Epidemiology, University Campus Bio-Medico of Rome, 00128 Lazio, Italy
DOI: 10.31083/j.ejgo4205129 Vol.42,Issue 5,October 2021 pp.844-849
Submitted: 29 January 2021 Accepted: 20 May 2021
Published: 15 October 2021
*Corresponding Author(s): Plotti Francesco E-mail: f.plotti@unicampus.it
Objective: To assess the role of HE4 (Human epidydimal protein 4) marker as predictor of response to platinum based chemotherapy. Methods: In the current observational prospective study, 35 patients affected by High Grade Serous Ovarian Cancer (HGSOC) were enrolled; among these, 17 patients were platinum sensitive, while 18 were platinum resistant. HE4 levels were measured before surgery, at the III and at the VI cycle of chemotherapy. Results: The reduction of 50% or more of HE4 levels at the III cycle of chemotherapy showed a specificity of 100% and a sensitivity of 27%. The negativization (<70 pmol/L) of HE4 at the III cycle of chemotherapy showed a specificity of 100%, with a sensitivity of 39%, in predicting chemotherapy response, while the same parameter at the VI cycle showed a speci-ficity of 82% and a sensitivity of 67%. Moreover the ROC analysis identified the HE4 cut-off value of 62.79 pmol/L as the best cut-off in predicting chemotherapy response, with a sensitivity of 72% and a specificity of 88% at the III cycle. Discussion: Our results suggest that HE4 levels during first-line chemotherapy, in particular at the III cycle, could predict chemotherapy response in HGSOC patients.
HE4; Ovarian cancer; Marker; Chemotherapy; Platinum
Plotti Francesco,Bartolone Martina,Terranova Corrado,Guzzo Federica,De Cicco Nardone Carlo,Montera Roberto,Molinaro Michele,Ciccozzi Massimo,Benvenuto Domenico,Di Donato Violante,Benedetti Panici Pierluigi. Effectiveness of human epididymis protein 4 (HE4) as predictor of response to first line platinum based chemotherapy. European Journal of Gynaecological Oncology. 2021. 42(5);844-849.
[1] Webb PM, Jordan SJ. Epidemiology of epithelial ovarian cancer. Best Practice & Research Clinical Obstetrics & Gynaecology. 2017; 41: 3–14.
[2] Lisio M, Fu L, Goyeneche A, Gao Z, Telleria C. High-grade serous ovarian cancer: basic sciences, clinical and therapeutic stand-points. International Journal of Molecular Sciences. 2019; 20: 952.
[3] Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simonsen E, et al. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. Journal of the National Cancer Institute. 2000; 92: 699–708.
[4] Orr B, Edwards RP. Diagnosis and Treatment of Ovarian Cancer. Hematology Oncology Clinics of North America. 2018; 32: 943–964.
[5] Eisenhauer EA. Real-world evidence in the treatment of ovarian cancer. Annals of Oncology. 2017; 28: viii61–viii65.
[6] Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemotherapy and Pharmacology. 2018; 81: 17–38.
[7] Rustin GJS, Nelstrop AE, Tuxen MK, Lambert HE. Defining progression of ovarian carcinoma during follow-up according to CA 125: a North Thames Ovary Group study. Annals of Oncology. 1996; 7: 361–364.
[8] Nustad K, Bast RC Jr, Brien TJ, Nilsson O, Seguin P, Suresh MR, et al. Specificity and affinity of 26 monoclonal antibodies against the CA 125 antigen: first report from the ISOBM TD-1 workshop. In-ternational Society for Oncodevelopmental Biology and Medicine. Tumor Biology. 1996; 17: 196–219.
[9] Urban N. Specific keynote: ovarian cancer risk assessment and the potential for early detection. Gynecologic Oncology. 2003; 88: S75–S79.
[10] Scaletta G, Plotti F, Luvero D, Capriglione S, Montera R, Miranda A, et al. The role of novel biomarker he4 in the diagnosis, prognosis and follow-up of ovarian cancer: a systematic review. Expert Review of Anticancer Therapy. 2017; 17: 827–839.
[11] Plotti F, Guzzo F, Schirò T, Terranova C, De Cicco Nardone C, Montera R, et al. Role of human epididymis protein 4 (he4) in detecting recurrence in CA125 negative ovarian cancer patients. International Journal of Gynecological Cancer. 2019; ijgc-2019-000211.
[12] Hamed EO, Ahmed H, Sedeek OB, Mohammed AM, Abd-Alla AA, Abdel Ghaffar HM. Significance of HE4 estimation in comparison with CA125 in diagnosis of ovarian cancer and assessment of treatment response. Diagnostic Pathology. 2013; 8: 11.
[13] Angioli R, Plotti F, Capriglione S, Aloisi A, Montera R, Luvero D, et al. Can the preoperative he4 level predict optimal cytoreduction in patients with advanced ovarian carcinoma? Gynecologic Oncology. 2013; 128: 579–583.
[14] Steffensen KD, Waldstrøm M, Brandslund I, Petzold M, Jakobsen A. The prognostic and predictive value of combined HE4 and CA-125 in ovarian cancer patients. International Journal of Gynecological Cancer. 2012; 22: 1474–1482.
[15] Aarenstrup Karlsen M, Høgdall C, Nedergaard L, Philipsen Prahm K, Schou Karlsen NM, Weng Ekmann-Gade A, et al. He4 as a predictor of adjuvant chemotherapy resistance and survival in patients with epithelial ovarian cancer. Acta Pathologica, Microbiologica, et Immunologica Scandinavica. 2016; 124: 1038–1045.
[16] Pelissier A, Roulot A, Guéry B, Bonneau C, Bellet D, Rouzier R. Serum CA125 and he4 levels as predictors for optimal interval surgery and platinum sensitivity after neoadjuvant platinum-based chemotherapy in patients with advanced epithelial ovarian cancer. Journal of Ovarian Research. 2016; 9: 61.
[17] Chudecka-Głaz A, Cymbaluk-Płoska A, Wężowska M, Menkiszak J. Could he4 level measurements during first-line chemotherapy predict response to treatment among ovarian cancer patients?PLoS ONE. 2018; 13: e0194270.
[18] Chudecka-Głaz AM, Cymbaluk-Płoska AA, Menkiszak JL, Sompolska-Rzechuła AM, Tołoczko-Grabarek AI, Rzepka-Górska IA. Serum he4, CA125, YKL-40, bcl-2, cathepsin-L and prediction optimal debulking surgery, response to chemotherapy in ovarian cancer. Journal of Ovarian Research. 2014; 7: 62.
[19] Moore RG, Hill EK, Horan T, Yano N, Kim K, MacLaughlan S, et al. HE4 (WFDC2) gene overexpression promotes ovarian tumor growth. Scientific Reports. 2014; 4: 3574.
[20] Wang H, Zhu L, Gao J, Hu Z, Lin B. Promotive role of recombinant he4 protein in proliferation and carboplatin resistance in ovarian cancer cells. Oncology Reports. 2015; 33: 403–412.
[21] Zhu L, Gao J, Hu Z, Schwab CL, Zhuang H, Tan M, et al. Membranous expressions of Lewis y and CAM-DR-related markers are independent factors of chemotherapy resistance and poor prognosis in epithelial ovarian cancer. American Journal of Cancer Research. 2015; 5: 830–843.
[22] Ribeiro JR, Schorl C, Yano N, Romano N, Kim KK, Singh RK, et al. HE4 promotes collateral resistance to cisplatin and paclitaxel in ovarian cancer cells. Journal of Ovarian Research. 2016; 9: 28.
[23] Lee S, Choi S, Lee Y, Chung D, Hong S, Park N. Role of human epididymis protein 4 in chemoresistance and prognosis of epithelial ovarian cancer. Journal of Obstetrics and Gynaecology Research. 2017; 43: 220–227.
[24] Piccart MJ, Bertelsen K, James K, Cassidy J, Mangioni C, Simon-sen E, et al. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. Journal of the National Cancer Institute. 2000; 92: 699–708.
[25] Neijt JP, Engelholm SA, Tuxen MK, Sorensen PG, Hansen M, Sessa C, et al. Exploratory phase III study of paclitaxel and cisplatin versus paclitaxel and carboplatin in advanced ovarian cancer. Journal of Clinical Oncology. 2000; 18: 3084–3092.
[26] Ozols RF, Bundy BN, Greer BE, Fowler JM, Clarke-Pearson D, Burger RA, et al. Phase III trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. Journal of Clinical Oncology. 2003; 21: 3194–3200.
[27] McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, et al. Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. New England Journal of Medicine. 1996; 334: 1–6.
[28] Uziely B, Formenti SC, Watkins K, Mazumder A, Muggia FM. Calvert’s formula and high-dose carboplatin. Journal of Clinical Oncology. 1994; 12: 1740–1741.
[29] van Dalen A, Favier J, Burges A, Hasholzner U, de Bruijn HW, Dobler-Girdziunaite D, et al. Prognostic significance of CA 125and TPS levels after 3 chemotherapy courses in ovarian cancer patients. Gynecologic Oncology. 2000; 79: 444–450.
[30] Moore RG, Brown AK, Miller MC, Skates S, Allard WJ, Verch T, et al. The use of multiple novel tumor biomarkers for the detection of ovarian carcinoma in patients with a pelvic mass. Gynecologic Oncology. 2008; 108: 402–408.
[31] Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European Journal of Cancer. 2009; 45: 228–247.
[32] Pujade-Lauraine E, Banerjee S, Pignata S. Management of platinum-resistant, relapsed epithelial ovarian cancer and new drug perspectives. Journal of Clinical Oncology. 2019; 37: 2437–2448.
[33] Friedlander M, Trimble E, Tinker A, Alberts D, Avall-Lundqvist E, Brady M, et al. Clinical trials in recurrent ovarian cancer. International Journal of Gynecological Cancer. 2011; 21: 771–775.
[34] Colombo N, Sessa C, Bois AD, Ledermann J, McCluggage W, Mc-Neish I, et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. International Journal of Gynecologic Cancer. 2019; 29: 728–760.
[35] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA: A Can-cer Journal for Clinicians. 2018; 68: 7–30.
[36] Davis A, Tinker AV, Friedlander M. “Platinum resistant” ovarian cancer: what is it, who to treat and how to measure benefit? Gynecologic Oncology. 2014; 133: 624–631.
[37] Plotti F, Capriglione S, Terranova C, Montera R, Aloisi A, Damiani P, et al. Does HE4 have a role as biomarker in the recurrence of ovarian cancer? Tumour Biology. 2013; 33: 2117–2123.
[38] Angioli R, Plotti F, Capriglione S, Aloisi A, Montera R, Luvero D, et al. Can the preoperative HE4 level predict optimal cytoreduction in patients with advanced ovarian carcinoma? Gynecologic Oncology. 2013; 128: 579–583.
[39] Plotti F, Bartolone M, Terranova C, Luveroe D, Scaletta G, Gatti A, et al. Role of human epididymis protein 4 (HE4) as predictor of response to platinum based chemotherapy: a systematic review of literature. European Journal of Gynaecological Oncology. 2020; 889–896.
[40] Brewer M, Angioli R, Scambia G, Lorusso D, Terranova C, Panici PB, et al. Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: a randomized phase II study. Gynecologic Oncology. 2020; 156: 523–529.
[41] Lazzaro C, Plotti F, Capriglione S, Ferrario M, Angioli R. Cost of illness of advanced ovarian carcinoma in Italy: results of an empirical, single-centre study, 2015. Farmeconomia Health Economics and Therapeutic Pathways. 2015; 16: 61–76.
[42] Plotti F, Terranova C, Guzzo F, De Cicco Nardone C, Luvero D, Bartolone M, et al. Role of BRCA mutation and HE4 in predicting chemotherapy response in ovarian cancer: a retrospective pilot study. Biomedicines. 2021; 9: 55.
Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.
Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.
Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.
JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.
Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.
BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.
Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.
Top