LAPTM4B gene copy number gain is associated with inferior response to anthracycline-based chemotherapy in hormone receptor negative breast carcinomas.

Autor: Rusz O; Department of Oncotherapy, University of Szeged, Korányi fasor 12, Szeged, 6720, Hungary., Papp O; 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary., Vízkeleti L; 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary.; MTA-SE-NAP B Brain Metastasis Research Group, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary., Molnár BÁ; 1st Department of Surgery, Semmelweis University, Üllői út 78, Budapest, 1082, Hungary., Bende KC; 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary., Lotz G; 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary., Ács B; 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary., Kahán Z; Department of Oncotherapy, University of Szeged, Korányi fasor 12, Szeged, 6720, Hungary., Székely T; 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary., Báthori Á; Department of Pathology, University of Szeged, Állomás u. 2, Szeged, 6725, Hungary., Szundi C; 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary., Kulka J; 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary., Szállási Z; 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary.; MTA-SE-NAP B Brain Metastasis Research Group, 2nd Department of Pathology, Semmelweis University, Budapest, Hungary.; Department of Bio and Health Informatics, Technical University of Denmark, Kemitorvet 208, 2800, Lyngby, Denmark.; Computational Health Informatics Program, Boston Children's Hospital, Harvard Medical School, Harvard University, 300 Longwood Avenue, Boston, MA, 02115, USA., Tőkés AM; 2nd Department of Pathology, Semmelweis University, Üllői út 93, Budapest, 1091, Hungary. tokesa1972@yahoo.co.uk.
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2018 Jul; Vol. 82 (1), pp. 139-147. Date of Electronic Publication: 2018 May 16.
DOI: 10.1007/s00280-018-3602-z
Abstrakt: Purpose: 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.).
Results: 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.
Conclusion: 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.
Databáze: MEDLINE
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