LAPTM4B gene copy number gain is associated with inferior response to anthracycline-based chemotherapy in hormone receptor negative breast carcinomas
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To determine the associations between lysosomal-associated transmembrane protein 4b (LAPTM4B) gene copy number and response to different chemotherapy regimens in hormone receptor negative (HR-) primary breast carcinomas.
Patients and methods
Two cohorts were analyzed: (1) 69 core biopsies from HR-breast carcinomas treated with neoadjuvant chemotherapy (anthracycline based in 72.5% of patients and non-anthracycline based in 27.5% of patients). (2) Tissue microarray (TMA) of 74 HR-breast carcinomas treated with adjuvant therapy (77.0% of the patients received anthracycline, 17.6% of the patients non-anthracycline-based therapy, and in 5.4% of the cases, no treatment data are available). Interphase FISH technique was applied on pretreatment core biopsies (cohort I) and on TMAs (cohort II) using custom-made dual-labelled FISH probes (LAPTM4B/CEN8q FISH probe Abnova Corp.).
In the neoadjuvant cohort in the anthracycline-treated group, we observed a significant difference (p = 0.029) of average LAPTM4B copy number between the non-responder and pathological complete responder groups (4.1 ± 1.1 vs. 2.6 ± 0.1). In the adjuvant setting, the anthracycline-treated group of metastatic breast carcinomas was characterized by higher LAPTM4B copy number comparing to the non-metastatic ones (p = 0.046). In contrast, in the non-anthracycline-treated group of patients, we did not find any LAPTM4B gene copy number differences between responder vs. non-responder groups or between metastatic vs. non-metastatic groups.
Our results confirm the possible role of the LAPTM4B gene in anthracycline resistance in HR− breast cancer. Analyzing LAPTM4B copy number pattern may support future treatment decision.
KeywordsBreast carcinomas LAPTM4B Anthracycline-based chemotherapy FISH
We would like to thank Erzsébet Kovács for technical assistance and Stefan Vari-Kakas for manuscript revision.
This study was funded by seven grants: (1) New National Excellence Program (ÚNKP-17-4-II-SE-65); (2) New National Excellence Program (ÚNKP-17-4-III-SE-71); (3) National Talent Program (NTP-NFTÖ-17-B-0308) of the Ministry of Human Capacities; (4) NVKP_16-1-2016-0004; (5) STIA 19/2017, 6800313113, 68003F0043; (6) The Research and Technology Innovation Fund (KTIA_NAP_13-2014-0021 to Z.S.). (7) Breast Cancer Research Foundation (Z.S.).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest. Orsolya Rusz declares that she has no conflict of interest. Orsolya Papp declares that she has no conflict of interest. Laura Vízkeleti declares that she has no conflict of interest. Béla Ákos Molnár declares that he has no conflict of interest. Kristóf Csaba Bende declares that he has no conflict of interest. Gábor Lotz declares that he has no conflict of interest. Balázs Ács declares that he has no conflict of interest. Zsuzsanna Kahán declares that she has no conflict of interest. Tamás Székely declares that he has no conflict of interest. Ágnes Báthori declares that she has no conflict of interest. Csilla Szundi declares that she has no conflict of interest. Janina Kulka declares that she has no conflict of interest. Zoltán Szállási declares that he has no conflict of interest. Anna-Mária Tőkés declares that she has no conflict of interest.
The study was ethically approved by the Semmelweis University Institutional Review Board (SE-TUKEB 120/2013). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
The breast carcinoma cases were retrospectively selected from prospectively maintained databases (Primary breast carcinoma cases were diagnosed between 1999 and 2016), and accordingly, informed consent was not obtained from all individual participants included in the study.
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