HSP70 In triple negative breast cancer: Prognostic value and clinical significance

Ana Car Peterko; Koraljka Rajković-Molek; Tamara Gulić; Danijela Veljković Vujaklija; Ingrid Belac Lovasić; Franjo Lovasić; Elvira Mustać; Manuela Avirović

doi:10.1016/j.prp.2022.154127

HSP70 In triple negative breast cancer: Prognostic value and clinical significance

Pathol Res Pract. 2022 Oct:238:154127. doi: 10.1016/j.prp.2022.154127. Epub 2022 Sep 15.

Authors

Ana Car Peterko¹, Koraljka Rajković-Molek², Tamara Gulić³, Danijela Veljković Vujaklija⁴, Ingrid Belac Lovasić⁵, Franjo Lovasić¹, Elvira Mustać⁶, Manuela Avirović⁷

Affiliations

¹ Clinical Hospital Center Rijeka, Department of General Surgery and Surgical Oncology, Rijeka, Croatia.
² Clinical Hospital Center Rijeka, Clinical Department of Pathology and Cytology, Rijeka, Croatia. Electronic address: koraljkarm@gmail.com.
³ University of Rijeka, Faculty of Medicine, Department of Physiology Immunology and Pathophysiology, Rijeka, Croatia.
⁴ Clinical Hospital Center Rijeka, Clinical Department of Radiology, Rijeka, Croatia.
⁵ Clinical Hospital Center Rijeka, Clinical Department of Radiotherapy and Oncology, Rijeka, Croatia.
⁶ Clinical Hospital Center Rijeka, Clinical Department of Pathology and Cytology, Rijeka, Croatia.
⁷ Clinical Hospital Center Rijeka, Clinical Department of Pathology and Cytology, Rijeka, Croatia; University of Rijeka, Faculty of Medicine, Department of Pathology, Rijeka, Croatia.

PMID: 36174439
DOI: 10.1016/j.prp.2022.154127

Abstract

Background: Triple-negative breast cancer (TNBC) has the worst prognosis and the highest immunogenic potential of all breast cancer subtypes. It is characterized by a lack of estrogen and progesterone receptors as well as HER2. A major component of the tumor microenvironment (TME) of TNBC is tumor-infiltrating lymphocytes (TILs). A chaperone heat shock protein 70 (HSP70) is involved in several pathways that enable tumour growth and progression, as well as in immune modulation.

Methods: Immunohistochemical analysis of HSP70 expression in immune cells, as well as expression of immunosuppressive markers CTLA4 and PD-L1 and major TILs components: CD8, CD4 and Tregs were analyzed in the superficial and deep tumor layer of primary TNBC and compared with established clinicopathological parameters. Clinical data and surgical tissue samples from 68 TNBC patients who underwent initial surgery were included in the analysis and 36 control samples from benign breast tissue biopsies.

Results: A higher expression of TILs, CD4, CD8 and PD-L1 was found in the invasive tumor front (ITF), as compared to the tumor center (TC) (p < 0001). HSP70 positive immune cells (HSP70(+) IC) in TC were associated with adverse clinical and pathological markers: higher stage of disease (P = 0.013), higher grade (P = 0.05) and a higher pN status (P < 0.001). In addition, higher expression of HSP70(+) IC from TC was correlated with the higher expression of FOXP3(+)T cells both in ITF (N = 61, rho=0.42, p < 0.001) and in metastatic tissue from the draining lymph nodes (N = 13, rho=0.61, P = 0.026).

Conclusion: Correlations between HSP70 immune cells expression and individual TILs components support the hypothesis of its active role in inducing immunosuppression and tumor progression. Routine determination of HSP70 expression, in immune cells of TC, may be of added value in the clinical decision-making process concerning axillary surgery.

Keywords: HSP70; Immunohistochemistry; Invasive tumor front; Prognosis; Triple-negative breast cancer; Tumor infiltrating lymphocytes.