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Immunophenotypic features of molecular subtypes of breast cancer

https://doi.org/10.33667/2078-5631-2022-26-20-26

Abstract

Introduction. Currently, immunotropic drugs are used in the modern strategy of cancer treatment. Importance is given to immunological markers of the tumor, which may be associated with the prognosis of the disease, the effectiveness of treatment. Therefore, the study of tumor immunophenotype is one of the leading scientific directions. Of particular interest is the study of the immunophenotypic characteristics of breast cancer depending on its biological subtype.

Purpose. To evaluate the frequency of expression of HLA-I, HLA-II, CD71, MUC1, Pgp170 molecules by breast cancer cells and determine their relationship with the molecular biological subtype of the tumor.

Materials and methods. This study included 120 patients with breast cancer who received treatment at the National Medical Research Centre of Oncology n. a. N. N. Blokhin (Moscow, Russia). Tumor stages II and III prevailed: 56.7 % and 33.4 %, respectively. A moderate degree of differentiation (G2) was more often noted. The luminal subtype was 58.3 % (n = 70), non-luminal – in 41.7 % (n = 50). Immunophenotyping of the primary tumor was performed by immunofluorescence on cryostat sections. The reaction was evaluated using a Zeiss luminescent microscope (Axioskop, Germany). The frequency of expression of HLA-I and class II molecules was studied depending on the clinical and morphological characteristics of breast cancer. The frequency of expression of HLA-I, HLA-II, CD71, MUC1, Pgp170 molecules depending on the molecular subtype of breast cancer was studied.

Results. The absence of molecules of the major histocompatibility complex of class I and II on breast cancer cells was found in 89.6 % of the samples. The monomorphic expression was observed in 23.4 % of cases. In the luminal subtype, HLA-II class molecules were expressed more often: in total, mosaic and monomorphic types of reactions were observed in 30.5 % (20/65) of cases. With non-luminal – 20.0 % (10/47) of cases. The frequency of expression of the transferrin receptor is significantly higher in the luminal subtype than in the non-luminal subtype: 85.9 % (n = 5) and 65.2 % (n = 30), p = 0.011. Luminal breast cancer cells express transferrin receptors predominantly monomorphically: 75.4 % (n = 49) vs 43.5 % (n = 20) in the non-luminal subtype, p = 0.003. The MUC 1 expressing monomorphically tumors is higher in luminal cancer: 83.3 % (n = 35) versus 65 % (n = 26) in the non-luminal subtype. Monomorphic expression of Pgp170 is more often observed in luminal breast cancer.

Conclusion. Luminal breast cancer is characterized by unfavorable prognostic immunophenotypic features. In the luminal subtype, expression of CD71 is more often observed, predominantly monomorphic. In the non-luminal subtype, expression of Pgp170 is observed less frequently. No statistically significant differences between the molecular subtypes in terms of the level of expression of HLA-I and class II molecules were found.

About the Authors

S. V. Chulkova
National Medical Research Centre of Oncology n. a. N. N. Blokhin; Russian National Research Medical University n. a. N. I. Pirogov
Russian Federation

Chulkova Svetlana V., PhD Med, associate professor, senior researcher at Laboratory of Нaematopoiesis Immunology;  associate professor at Dept of Oncology and Radiotherapy of Medical Faculty

Moscow



E. N. Sholokhova
National Medical Research Centre of Oncology n. a. N. N. Blokhin
Russian Federation

Sholokhova Elena N., PhD Med, leading researcher at Laboratory of Нaematopoiesis Immunology

Moscow



I. V. Poddubnaya
Russian Medical Academy for Continuing Professional Education
Russian Federation

Poddubnaya Irina V., DM Sci (habil.), professor, academician of RAS, vice-rector for Clinical Work and International Cooperation, head of Dept of Oncology and Palliative Medicine

Moscow



E. V. Artamonova
National Medical Research Centre of Oncology n. a. N. N. Blokhin; Russian National Research Medical University n. a. N. I. Pirogov
Russian Federation

Artamonova Elena V., DM Sci (habil.), head of Dept of Chemotherapy No. 1; professor at Dept of Oncology and Radiotherapy of Medical Faculty

Moscow



A. V. Semyanikhina
National Medical Research Centre of Oncology n. a. N. N. Blokhin; Medical and Genetic Research Centre n. a. academician N. P. Bochkov
Russian Federation

Semyanikhina Alexandra V., PhD Med, associate professor, research scientist at Laboratory of Нaematopoiesis Immunology; assistant at Dept of Oncogenetics of Institute of Higher and Additional Professional Education

Moscow



I. S. Stylidi
National Medical Research Centre of Oncology n. a. N. N. Blokhin; Russian National Research Medical University n. a. N. I. Pirogov
Russian Federation

Stilidi Ivan S., DM Sci (habil.), professor, academician of RAS, director; head of Dept of Oncology and Radiotherapy of Medical Faculty

Moscow



N. N. Tupitsyn
National Medical Research Centre of Oncology n. a. N. N. Blokhin
Russian Federation

Tupitsyn Nikolai N., DM Sci (habil.), professor, head of Laboratory of Нaematopoiesis Immunology

Moscow



References

1. Hyuna Sung, Jacques Ferlay, Rebecca L. Siegel, Mathieu Laversanne, Isabelle Soerjomataram,; Ahmedin Jemal, Freddie Bray. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. Ca Cancer J Clin 2021; 71: 209–249.

2. McCormack V, McKenzie F, Foerster M, Zietsman A, Galukande M, Adisa C, et al. Breast cancer survival and survival gap apportionment in sub-Saharan Africa (ABC-DO): a prospective cohort study. The Lancet Global Health. 2020; 8 (9): e1203–12. http://www.ncbi.nlm.nih.gov/pubmed/32827482

3. Ginsburg O, Yip CH, Brooks A, Cabanes A, Caleffi M, Dunstan Yataco JA, et al. Breast cancer early detection: A phased approach to implementation. Cancer. 2020; 126. Suppl. 10: 237993. http://www.ncbi.nlm.nih.gov/pubmed/32348566

4. Mutebi M, Anderson BO, Duggan C, Adebamowo C, Agarwal G, Ali Z, et al. Breast cancer treatment: A phased approach to implementation. Cancer. 2020; 126. Suppl. 10: 236578. http://www.ncbi.nlm.nih.gov/pubmed/32348571

5. Blum J. S., Wearsch P.A., Cresswell P. Pathways of antigen processing. Annu. Rev. Immunol. 2013, 31, 443–473.

6. Leung TH, Tang HW, Siu MK, Chan DW, Chan KK, Cheung AN, Ngan HY. CD71+ Population Enriched by HPV-E6 Protein Promotes Cancer Aggressiveness and Radioresistance in Cervical Cancer Cells. Mol Cancer Res. 2019; 17 (9): 1867–1880. DOI: 10.1158/1541–7786.MCR-19–0068. PMID: 31235657.

7. Chen JQ, Russo J. Dysregulation of glucose transport, glycolysis, TCA cycle and glutaminolysis by oncogenes and tumor suppressors in cancer cells. Biochim Biophys Acta. 2012; 1826 (2): 370–384. DOI: 10.1016/j.bbcan.2012.06.004.

8. Shukla A, Cloutier M, Santharam A.M. et al. The MHC Class-I Transactivator NLRC 5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy. Int J Mol Sci. 2021 Feb 17; 22 (4): 1964. DOI: 10.3390/ijms22041964. PMID: 33671123.

9. Sabbatino F., Liguori L., Polcaro G et al. Role of Human Leukocyte Antigen System as A Predictive Biomarker for Checkpoint-Based Immunotherapy in Cancer Patients. Int. J. Mol. Sci. 2020, 21, 7295. DOI: 10.3390/ijms21197295.

10. Kang MK, Hur BI, Ko MH, Kim CH, Cha SH, Kang SK. Potential identity of multi-potential cancer stem-like subpopulation after radiation of cultured brain glioma. BMC Neurosci 2008; 9: 15.

11. Artamonova E.V. The role of immunophenotyping in the diagnosis and prognosis of breast cancer. Immunology of Hematopoiesis. 2009; 1 (9): 8–52.

12. Engai D. A., Poddubnaya I. V., Tupitsyn N. N., Mechetner E. B. Clinical and immunological significance of MDR1/PGP170 in breast cancer. Tumors of the Reproductive System. 2008. 3: 41–43.

13. Ryabchikov D.A. Luminal breast cancer: clinical, molecular biological, genetic features and prognosis. Diss. Doc. Med. Sciences. M. 2017. 262 p.

14. Burov D.A., Beznos O.A., Vorotnikov I.K., Selchuk V. Yu., Tupitsyn N.N. Clinical significance of the expression of histocompatibility molecules on breast cancer cells. Immunology of Hematopoiesis. 2016, 2 (14): 33–53.

15. Berishvili A.I., Tupitsyn N.N., Laktionov K.P. Immunophenotypic characteristics of the edematous-infiltrative form of breast cancer. Tumors of the female reproductive system. 2009. 3–4: 15–19.

16. Sinn B.V., Weber K.E., Schmitt W.D. et al. Human leucocyte antigen class I in hormone receptor-positive, HER2-negative breast cancer: association with response and survival after neoadjuvant chemotherapy. Breast Cancer Res. 21, 142, 2019. DOI: 10.1186/s13058–019–1231-z.

17. Martin H.P., Brian L.H., Hans Ch.B. et al. Downregulation of antigen presentation-associated pathway proteins is linked to poor outcome in triple-negative breast cancer patient tumors, OncoImmunology, 2017; 6: 5, e1305531, DOI: 10.1080/2162402X.2017.1305531.

18. Ryabchikov D. A., Beznos O. A., Dudina I. A., Vorotnikov I. K., Denchik D. A., Chulkova S.V., Talipov O.A., Tupitsyn N.N. Disseminated tumor cells in patients with luminal breast cancer. Russian Biotherapeutic Journal. 2018; 17 (1): 53–57 (In Russ.). DOI: 10.17650/1726–9784–2018–17–1–53–57.

19. Daniels TR, Delgado T, Rodriguez JA, Helguera G, Penichet ML. The transferrin receptor part I: biology and targeting with cytotoxic antibodies for the treatment of cancer. Clin Immunol. (2006) 121: 144–58. DOI: 10.1016/j.clim.2006.06.010.

20. Shen Y, Li X, Dong D, Zhang B, Xue Y, Shang P. Transferrin receptor 1 in cancer: a new sight for cancer therapy. Am J Cancer Res. (2018) 8: 916–31.

21. Basuli D, Tesfay L, Deng Z, Paul B, Yamamoto Y, Ning G, et al. Iron addiction: a novel therapeutic target in ovarian cancer. Oncogene. (2017) 36: 4089–99. DOI: 10.1038/onc.2017.11.

22. Habashy H. O., Powe D. G., Staka C. M. et al. Transferrin receptor (CD 71) is a marker of poor prognosis in breast cancer and can predict response to tamoxifen. Breast Cancer Res Treat 119, 283 (2010). https://doi.org/10.1007/s10549–009–0345-x

23. Riganti C, Gazzano E, Polimeni M, et al. The pentose phosphate pathway: an antioxidant defense and a crossroad in tumor cell fate. Free Radic Biol Med. 2012; 53 (3): 421–436. DOI: 10.1016/j.freeradbiomed.2012.05.006.

24. Baryshnikova M.A., Baryshnikov A. Yu., Afanas’eva D.A. Molecular mechanisms of overcoming multidrug resistance by liposomal anticancer drugs. Russian Biotherapeutic Journal. 2015; 14 (1): 3–10. https://doi.org/10.17650/1726–9784–2015–14–1–3–10

25. Anna M. Badowska-Kozakiewicz, Maria Sobol, and Janusz Patera Expression of multidrug resistance protein P-glycoprotein in correlation with markers of hypoxia (HIF‑1α, EPO, EPO-R) in invasive breast cancer with metastasis to lymph nodes. Arch Med Sci. 13 (6): 1303–1314. DOI: 10.5114/aoms.2016.62723. PMCID: PMC5701689. PMID: 29181060.

26. Yomna S. Abd El-Aziz, Andrew J. Spillane, Patric J. Jansson. Role of ABCB1 in mediating chemoresistance of triple-negative breast cancers. Bioscience Reports (2021) 41: 1–10. BSR20204092. https://doi.org/10.1042/BSR20204092

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Review

For citations:


Chulkova S.V., Sholokhova E.N., Poddubnaya I.V., Artamonova E.V., Semyanikhina A.V., Stylidi I.S., Tupitsyn N.N. Immunophenotypic features of molecular subtypes of breast cancer. Medical alphabet. 2022;(26):20-26. (In Russ.) https://doi.org/10.33667/2078-5631-2022-26-20-26

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ISSN 2078-5631 (Print)
ISSN 2949-2807 (Online)