TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers
Abstract Objective Relapsed epithelial ovarian cancer (EOC) is frequently treated with pegylated liposomal doxorubicin (PLD). Unfortunately, most patients do not benefit from treatment. Prediction of response is crucial to optimize PLD use and avoid unnecessary toxicities. We aimed at assessing the...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Journal of Ovarian Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13048-019-0492-6 |
| _version_ | 1797965784033525760 |
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| author | Eleonora Ghisoni Furio Maggiorotto Fulvio Borella Gloria Mittica Sofia Genta Gaia Giannone Dionyssios Katsaros Alberto Sciarrillo Annamaria Ferrero Ivana Sarotto Jessica Erriquez Maria Flavia Di Renzo Massimo Aglietta Giorgio Valabrega |
| author_facet | Eleonora Ghisoni Furio Maggiorotto Fulvio Borella Gloria Mittica Sofia Genta Gaia Giannone Dionyssios Katsaros Alberto Sciarrillo Annamaria Ferrero Ivana Sarotto Jessica Erriquez Maria Flavia Di Renzo Massimo Aglietta Giorgio Valabrega |
| author_sort | Eleonora Ghisoni |
| collection | DOAJ |
| description | Abstract Objective Relapsed epithelial ovarian cancer (EOC) is frequently treated with pegylated liposomal doxorubicin (PLD). Unfortunately, most patients do not benefit from treatment. Prediction of response is crucial to optimize PLD use and avoid unnecessary toxicities. We aimed at assessing the value of topoisomerase II alpha (TOP2A) expression as predictive marker of response to PLD-based therapy in patients with relapsed EOCs. Methods We retrospectively analyzed Formalin Fixed Paraffin Embedded (FFPE) tissues from 101 patients with platinum resistant (PR) or partially platinum-sensitive (PPS) EOCs treated with PLD-based chemotherapy beyond second line in three referral cancer centers between January 2010 and June 2018. TOP2A expression was measured by immunohistochemistry (IHC): images of each sample were acquired by optical microscope and analyzed by using automatic counter software. Correlation between TOP2A expression and response to PLD was assessed. Since no cut-off for positivity has been validated yet, we dichotomized TOP2A expression based on a cut-off of 18% (mean value in this study). Results TOP2A expression beyond cut-off was not prognostic for primary platinum-free interval in our series (p = 0.77) neither for optimal cytoreduction (p = 0.9). TOP2A > 18% was associated with a longer time to progression (TTP) following PLD-treatment, although not statistically significant (p = 0.394). No difference was observed between PR and PPS patients’ groups (p = 0.445 and p = 0.185, respectively). Not unexpectedly, patients with TOP2A expression > 18% treated with PLD monotherapy achieved a longer TTP compared with PLD-doublet therapy (p = 0.05). Conclusions Our data suggest that TOP2A status might predict activity of PLD in patients with PR/PPS EOCs. |
| first_indexed | 2024-04-11T02:05:31Z |
| format | Article |
| id | doaj.art-bebfb45ba0e44ba39276564ce30bfd33 |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-11T02:05:31Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-bebfb45ba0e44ba39276564ce30bfd332023-01-03T03:12:12ZengBMCJournal of Ovarian Research1757-22152019-02-011211610.1186/s13048-019-0492-6TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancersEleonora Ghisoni0Furio Maggiorotto1Fulvio Borella2Gloria Mittica3Sofia Genta4Gaia Giannone5Dionyssios Katsaros6Alberto Sciarrillo7Annamaria Ferrero8Ivana Sarotto9Jessica Erriquez10Maria Flavia Di Renzo11Massimo Aglietta12Giorgio Valabrega13Department of Oncology, University of TorinoCandiolo Cancer Institute-FPO- IRCCSDepartment of Surgical Sciences, Gynecology, AOU Città della SaluteDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Surgical Sciences, Gynecology, AOU Città della SaluteDepartment of Surgical Sciences, Gynecology, AOU Città della SaluteDepartment of Gynecology and Obstetrics, University of Torino, Mauriziano HospitalCandiolo Cancer Institute-FPO- IRCCSCandiolo Cancer Institute-FPO- IRCCSDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoDepartment of Oncology, University of TorinoAbstract Objective Relapsed epithelial ovarian cancer (EOC) is frequently treated with pegylated liposomal doxorubicin (PLD). Unfortunately, most patients do not benefit from treatment. Prediction of response is crucial to optimize PLD use and avoid unnecessary toxicities. We aimed at assessing the value of topoisomerase II alpha (TOP2A) expression as predictive marker of response to PLD-based therapy in patients with relapsed EOCs. Methods We retrospectively analyzed Formalin Fixed Paraffin Embedded (FFPE) tissues from 101 patients with platinum resistant (PR) or partially platinum-sensitive (PPS) EOCs treated with PLD-based chemotherapy beyond second line in three referral cancer centers between January 2010 and June 2018. TOP2A expression was measured by immunohistochemistry (IHC): images of each sample were acquired by optical microscope and analyzed by using automatic counter software. Correlation between TOP2A expression and response to PLD was assessed. Since no cut-off for positivity has been validated yet, we dichotomized TOP2A expression based on a cut-off of 18% (mean value in this study). Results TOP2A expression beyond cut-off was not prognostic for primary platinum-free interval in our series (p = 0.77) neither for optimal cytoreduction (p = 0.9). TOP2A > 18% was associated with a longer time to progression (TTP) following PLD-treatment, although not statistically significant (p = 0.394). No difference was observed between PR and PPS patients’ groups (p = 0.445 and p = 0.185, respectively). Not unexpectedly, patients with TOP2A expression > 18% treated with PLD monotherapy achieved a longer TTP compared with PLD-doublet therapy (p = 0.05). Conclusions Our data suggest that TOP2A status might predict activity of PLD in patients with PR/PPS EOCs.http://link.springer.com/article/10.1186/s13048-019-0492-6Ovarian cancerTopoisomerase 2 alphaPegylated liposomal doxorubicin |
| spellingShingle | Eleonora Ghisoni Furio Maggiorotto Fulvio Borella Gloria Mittica Sofia Genta Gaia Giannone Dionyssios Katsaros Alberto Sciarrillo Annamaria Ferrero Ivana Sarotto Jessica Erriquez Maria Flavia Di Renzo Massimo Aglietta Giorgio Valabrega TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers Journal of Ovarian Research Ovarian cancer Topoisomerase 2 alpha Pegylated liposomal doxorubicin |
| title | TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers |
| title_full | TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers |
| title_fullStr | TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers |
| title_full_unstemmed | TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers |
| title_short | TOP2A as marker of response to pegylated lyposomal doxorubicin (PLD) in epithelial ovarian cancers |
| title_sort | top2a as marker of response to pegylated lyposomal doxorubicin pld in epithelial ovarian cancers |
| topic | Ovarian cancer Topoisomerase 2 alpha Pegylated liposomal doxorubicin |
| url | http://link.springer.com/article/10.1186/s13048-019-0492-6 |
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