Научная статья на тему 'Decrease Stiffness of Patients’ Breast Cancer Tissue During Neoadjuvant Therapy '

Decrease Stiffness of Patients’ Breast Cancer Tissue During Neoadjuvant Therapy Текст научной статьи по специальности «Медицинские технологии»

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Текст научной работы на тему «Decrease Stiffness of Patients’ Breast Cancer Tissue During Neoadjuvant Therapy »

B-O-13

BIOMEDICAL PHOTONICS

Decrease Stiffness of Patients' Breast Cancer Tissue During Neoadjuvant Therapy

A.A. Plekhanov1, E.V. Gubarkova1, M.A. Sirotkina1, V.V. Elagin1, A.A. Sovetsky2, D.A. Vorontsov3, A.Y. Bogomolova1, A.Y. Vorontsov3, S.V. Gamayunov3, V.Y. Zaitsev2, and N.D. Gladkova1

1- Privolzhsky Research Medical University, Nizhny Novgorod, Russia 2- Institute of Applied Physics of the Russian Academy of Sciences, Nizhny Novgorod, Russia 3- Nizhny Novgorod Regional Oncologic Hospital, Nizhny Novgorod, Russia

strike_gor@mail.ru

In the presented study, we demonstrate patients' clinical cases with diagnosed breast cancer and prescribed neoadjuvant (preoperative) chemotherapy (NACT). We examined tumor tissues taken by core needle biopsy before and during NACT. The studies were carried out using original home built multimodal optical coherence tomography system (IAP RAS, Nizhny Novgorod) [1] in the elastographic scanning mode - compression optical coherence elastography (OCE), which is described elsewhere [2, 3]. Multiphoton microscopy (MPM, LSM 880, Carl Zeiss, Germany) based on second harmonic generation and two-photon-excited fluorescence was used to assess connective tissue fibers and other breast cancer tissue. To determine the morphological features of the studied tissues, a histological study (with hematoxylin and eosin staining) was used. Previously, we have established the ranges of stiffness values for the morphological structures of breast cancer tissue [4]. Besides, we performed the studies of postoperative tumor samples of patients after treatment [5], where we found both the areas of very low stiffness values (Young's modulus) (less than 100 kPa) and medium stiffness values (~200-400 kPa) corresponding to necrotic tumor cells and connective tissue stromal fibers (that replace dead tumor cells), respectively.

In this study, we compared the elastic properties of tumors before and during NACT. According to the results of OCE studies, a decrease in stiffness values of the residual (saved after therapy) tumor cells was found, compared with stiffness of tumor cells before treatment. Areas of tumor cells with a stiffness of ~500-700 kPa prevailed, whereas before NACT, areas with a stiffness more 700 kPa prevailed. Histological examination of tumor tissue during NACT revealed a large number of dystrophic tumor cells (with destruction of cell nucleus - karyopyknosis or karyorrhexis). The study of tumor tissue with MPM before and during NACT revealed a change in mutual arrangement of tumor cells and connective tissue fibers: a transition from dense clusters of tumor cells lying among thick connective tissue fibers of the stroma to single cells densely surrounded by thin connective tissue fibers. Our further research will focus on the determination of the contribution of tumor cells and stromal fibers to the reduction of tumor stiffness during treatment. In addition, the correlation between tumor stiffness values on OCE and characteristics of connective tissue fibers on MPM will be determined.

The study was funded by the Russian Science Foundation, grant No. 18-75-10068.

[1] VM. Gelikonov, G.V. Gelikonov, P.A. Shilyagin. Optimization of Fizeau-based optical coherence tomography with a reference Michelson interferometer. Bulletin of the Russian Academy of Sciences: Physics, 72(1), 93-97, (2008).

[2] V.Y. Zaitsev, A.L. Matveyev, L.A. Matveev, G.V. Gelikonov, E.V. Gubarkova, N.D. Gladkova, A. Vitkin. Hybrid method of strain estimation in optical coherence elastography using combined sub-wavelength phase measurements and supra-pixel displacement tracking. Journal of Biophotonics, 9(5), 499-509, (2016).

[3] A.A. Plekhanov, M.A. Sirotkina, A.A. Sovetsky, E.V. Gubarkova, S.S. Kuznetsov, A.L. Matveyev, L.A. Matveev, E.V. Zagay-nova, N.D. Gladkova, VY. Zaitsev. Histological validation of in vivo assessment of cancer tissue inhomogeneity and automated morphological segmentation enabled by Optical Coherence Elastography. Scientific Reports, 10(1), 11781, (2020).

[4] E.V. Gubarkova, A.A. Sovetsky, VY. Zaitsev, A.L. Matveyev, D.A. Vorontsov, M.A. Sirotkina, L.A. Matveev, A.A. Plekhanov, N.P. Pavlova, S.S. Kuznetsov, A.Y. Vorontsov, E.V. Zagaynova, N.D. Gladkova. OCT-elastography-based optical biopsy for breast cancer delineation and express assessment of morphological/molecular subtypes. Biomedical Optics Express, 10(5), 2244-2263, (2019).

[5] A.A. Plekhanov, E.V. Gubarkova, A.A. Sovetsky, M.A. Sirotkina, S.S. Kuznetsov, L.A. Matveev, D.A. Vorontsov, A.L. Matveyev, E.V. Zagaynova, VY. Zaitsev, N.D. Gladkova. Improvement of breast cancer histological examination by means of multimodal OCT. Proceedings of SPIE, 11924, 119241H, 1-4, (2021).

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