title: Intratumoral morphological heterogeneity of breast cancer: neoadjuvant chemotherapy efficiency and multidrug resistance gene expression.
abstract: In this study, the influence of intratumoral morphological heterogeneity of breast cancer on neoadjuvant chemotherapy (NAC) efficiency was investigated. In particular, we analysed the association of NAC response and pre- and post-NAC expression of the main multidrug resistance (MDR) genes--ABCB1, ABCC1, ABCC5, ABCG1, and ABCG2, with the presence of different morphological structures in breast tumors. In addition, the expression of MDR genes was investigated in different morphological structures and in their microenvironment by comparing probes obtained using laser microdissection. The results of this study showed that tumors with alveolar structures were more frequently NAC-nonresponsive than cases without this structural type (p = 0.0028, Bonferroni-corrected p = 0.014). The presence of trabecular structures in breast tumors was also associated with chemoresistance (p = 0.0272, Bonferroni-corrected p = 0.136). High expression of MDR genes was not found in alveolar structures (including their microenvironment) and in tumors containing this structural type. In contrast, more active MDR genes and expression of the ABCB1 gene were found only in trabecular structures. Taken together, our data indicate that breast tumors with alveolar structures possess resistance to NAC, which is not related to high expression of MDR genes, whereas chemoresistance of tumors with trabecular structures can depend on the expression level of ABCB1.
authors.affiliation: 1] Department of Experimental Oncology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation [2] Laboratory of Translational Cell and Molecular Biomedicine, Tomsk State University, Tomsk, Russian Federation [3].
authors.forename: Evgeny V
authors.initials: EV
authors.lastname: Denisov
authors.affiliation: 1] Department of Experimental Oncology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation [2] Laboratory of Translational Cell and Molecular Biomedicine, Tomsk State University, Tomsk, Russian Federation [3].
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Litviakov
authors.affiliation: 1] Laboratory of Translational Cell and Molecular Biomedicine, Tomsk State University, Tomsk, Russian Federation [2] Department of Pathological Anatomy and Cytology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation [3] Department of Pathological Anatomy, Siberian State Medical University, Tomsk, Russian Federation.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Zavyalova
authors.affiliation: 1] Department of Pathological Anatomy and Cytology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation [2] Department of Pathological Anatomy, Siberian State Medical University, Tomsk, Russian Federation.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Perelmuter
authors.affiliation: 1] Department of Pathological Anatomy and Cytology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation [2] Department of Pathological Anatomy, Siberian State Medical University, Tomsk, Russian Federation.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Vtorushin
authors.affiliation: 1] Department of Experimental Oncology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation [2] Laboratory of Translational Cell and Molecular Biomedicine, Tomsk State University, Tomsk, Russian Federation.
authors.forename: Matvey M
authors.initials: MM
authors.lastname: Tsyganov
authors.affiliation: 1] Department of Experimental Oncology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation [2] Laboratory of Translational Cell and Molecular Biomedicine, Tomsk State University, Tomsk, Russian Federation.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Gerashchenko
authors.affiliation: Department of General Oncology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation.
authors.forename: Evgeny Yu
authors.initials: EY
authors.lastname: Garbukov
authors.affiliation: 1] Department of General Oncology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation [2] Department of Oncology, Siberian State Medical University, Tomsk, Russian Federation.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Slonimskaya
authors.affiliation: 1] Department of Experimental Oncology, Cancer Research Institute, Siberian Branch of the Russian Academy of Medical Sciences, Tomsk, Russian Federation [2] Laboratory of Translational Cell and Molecular Biomedicine, Tomsk State University, Tomsk, Russian Federation [3] Department of Oncology, Siberian State Medical University, Tomsk, Russian Federation.
authors.forename: Nadezhda V
authors.initials: NV
authors.lastname: Cherdyntseva
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000235:genetics
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; C513055:ABCB1 protein, human; C120809:ABCC5 protein, human; C419353:ABCG1 protein, human; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1
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