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The significance of intratumor morphological heterogeneity in breast cancer progression and pathogenetic mechanisms

Date

19 Dec 2015

Session

Poster presentation 1

Presenters

Evgeny Denisov

Citation

Annals of Oncology (2015) 26 (suppl_9): 153-155. 10.1093/annonc/mdv534

Authors

E.V. Denisov1, T.S. Gerashchenko1, L.A. Tashireva2, D.N. Pautova3, M.V. Zavyalova2, N. Cherdyntseva1, V.M. Perelmuter2

Author affiliations

  • 1 Laboratory For Translational Cellular And Molecular Biomedicine, Tomsk State University, 634050 - Tomsk/RU
  • 2 Department Of Pathological Anatomy And Cytology, Tomsk Cancer Research Institute, Tomsk/RU
  • 3 Department Of Cytology And Genetics, Tomsk State University, Tomsk/RU
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Aim/Background

In this study, we aimed to investigate the contribution of intratumor morphological heterogeneity to breast cancer (BC) metastasis and recurrence and to identify possible pathogenetic mechanisms.

Methods

441 patients with invasive carcinoma of no special type, who received neoadjuvant chemotherapy (NAC), have been enrolled. χ2 test and Kaplan-Meier analysis were used to estimate the association between the frequency of lymph node metastasis, distant metastasis and recurrence free survival and the presence of morphological structures (tubular, alveolar, trabecular, solid, and discrete) in breast tumors. Laser microdissection assisted transcriptome-wide array analysis was used to compare gene expression profile of different structures of three breast tumors and to identify differentially expressed genes.

Results

Patients with alveolar structures showed an increased frequency of lymph node metastasis (p < 0.00001). The same association was found for trabecular structures and discrete groups of tumor cells (p < 0.001). Interestingly, in NAC naive BC patients, the probability of lymphogenic metastasis was associated only with alveolar structures (Zavyalova et al., 2013). In NAC naïve group, no significant contribution of intratumor morphological heterogeneity to distant metastasis free survival has been also shown. In contrast, this study demonstrated that NAC treated patients with either alveolar or trabecular structures in breast tumors were characterized by decreased metastasis-free survival (p < 0.01). Interestingly, the association of structures with metastasis depended on chemotherapy response. No significant data regarding the contribution of different morphological structures to recurrence free survival has been found. Expression analysis showed that different morphological structures are characterized by specific expression profile and differentially expressed genes relating to BC invasion and metastasis; these data will be provided in detail in the presentation.

Conclusions

Intratumor morphological heterogeneity significantly contributes to breast cancer metastasis via up- or downregulation of specific genes in different morphological structures.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.

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