Relationship of the integrin profile of the primary tumor to metastasis to regional lymph nodes in breast cancer

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Abstract

Background. Breast cancer ranks first in the structure of cancer morbidity and mortality. Involvement of a large number of regional lymph nodes is considered a poor prognostic outcome. The mechanisms of development of lymphogenous metastasis in general and common in particular are not fully understood. Integrins are involved in the metastatic process by mediating tumor cell invasion and adhesion to vascular endothelium.

Aim. To study the role of integrins in lymphogenous metastasis.

Materials and methods. The study included 72 patients diagnosed with invasive breast carcinoma of no special type who underwent surgical treatment on the basis of the cancer research institute national research medical center. The average age reached 51.2 years. In accordance with the indications and morphological data, the patients underwent antitumor treatment. The tissue of the primary tumor obtained by trepanbiopsy. Histological and immunohistochemical examination was carried out according to the standard method. In primary tumor cells, the presence or absence of cytoplasmic or membrane/cytoplasmic colocalization of CD61 (Integrin beta 3), CD104 (Integrin beta 4), CD51 (Integrin alpha-V) expression was assessed. When statistically processing the results, Fisher's test and one-way regression analysis were used.

Results. In the N3 group, the frequency of cytoplasmic expression of CD 61 was higher at the trend level (40.9 and 18%; p=0.074). In the group of patients with N3, positive cytoplasmic expression of CD104 (37.5 and 15.0%; p=0.029) and membrane and cytoplasmic colocalization (52.6 and 15.1%; p=0.004) were more often detected. In the group with N1 and N2, membrane and cytoplasmic colocalization of CD104 expression was less common (15.8 and 54.7%; p=0.006). When studying the expression frequency of CD51 integrin, no significant differences were found depending on the severity of lymphogenous metastasis.

Conclusion. Expression of CD104 in primary tumor cells is strongly associated with widespread lymphogenous metastasis. Studies of the role of integrins in the development of lymphogenous metastasis are promising for predicting the prevalence of this process in the preoperative period and for searching for methods of influencing the tumor.

About the authors

Marina V. Zavyalova

Tomsk National Research Medical Center; Siberian State Medical University

Email: zavyalovamv@mail.ru
ORCID iD: 0000-0001-9429-9813

d. sci. (med.), prof.

Russian Federation, Tomsk

Gleb A. Kuznecov

Siberian State Medical University

Email: kuznetsov.gleb199710@gmail.com

graduate student

Russian Federation, Tomsk

Evgeniya S. Grigoryeva

Tomsk National Research Medical Center

Email: grigoryeva.es@gmail.com
ORCID iD: 0000-0003-4737-8951

cand. sci. (med.)

Russian Federation, Tomsk

Liubov A. Tashireva

Tomsk National Research Medical Center

Email: lkleptsova@mail.ru
ORCID iD: 0000-0003-2061-8417

d. sci. (med.)

Russian Federation, Tomsk

Dmitry S. Pismenny

Tomsk National Research Medical Center; Siberian State Medical University

Email: pismenniy.dmitry@yandex.ru
ORCID iD: 0000-0001-8973-8439

cand. sci. (med.)

Russian Federation, Tomsk

Vladimir M. Perelmuter

Tomsk National Research Medical Center

Author for correspondence.
Email: pvm@ngs.ru
ORCID iD: 0000-0002-7633-9620

d. sci. (med.), prof.

Russian Federation, Tomsk

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2. Fig. 1. Expression of integrins in the primary tumor: a – cytoplasmic expression of CD61; b – cytoplasmic/membrane colocalization of CD61 expression; c – cytoplasmic expression of CD104; d – cytoplasmic/membrane colocalization of CD104 expression; e – cytoplasmic expression of CD51; f – cytoplasmic/membrane colocalization of expression CD51. ×400.

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3. Fig. 2. Features of CD61, CD104, and CD51 expression in groups with and without metastases in regional lymph nodes, as well as with different severity of lymphogenic metastasis: a – the frequency of lymphogenous metastasis depending on the expression of CD61; b – frequency with N0, N1,2, N3 depending on the cytoplasmic expression of CD61; c – frequency with N0, N1,2, N3 depending on cytoplasmic and membrane co-expression of CD61.

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4. Fig. 3. The frequency of cytoplasmic expression and membrane/cytoplasmic colocalization of CD104 expression in patients with or without metastases in regional lymph nodes: a – the frequency of lymphogenous metastasis depending on the expression of CD104; b – frequency with N0, N1,2, N3 depending on the cytoplasmic expression of CD104; c – frequency with N0, N1,2, N3 depending on cytoplasmic and membrane co-expression of CD104.

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5. Fig. 4. The frequency of negative or positive cytoplasmic expression or membrane/cytoplasmic colocalization of CD51 in patient groups, depending on the presence or severity of lymphogenic metastasis: a – the frequency of lymphogenous metastasis depending on the expression of CD51; b – frequency with N0, N1,2, N3 depending on the cytoplasmic expression of CD51; c – frequency with N0, N1,2, N3 depending on cytoplasmic and membrane co-expression and CD51.

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