PT  - JOURNAL ARTICLE
AU  - Natalia Rusetska
AU  - Kamil Kowalski
AU  - Kamil Zalewski
AU  - Sebastian Zięba
AU  - Mariusz Bidziński
AU  - Krzysztof Goryca
AU  - Beata Kotowicz
AU  - Malgorzata Fuksiewicz
AU  - Janusz Kopczynski
AU  - Elwira Bakuła-Zalewska
AU  - Artur Kowalik
AU  - Magdalena Kowalewska
TI  - CXCR4/ACKR3/CXCL12 axis in the lymphatic metastasis of vulvar squamous cell carcinoma
AID  - 10.1136/jclinpath-2020-206917
DP  - 2021 Mar 09
TA  - Journal of Clinical Pathology
PG  - jclinpath-2020-206917
4099  - http://jcp.bmj.com/content/early/2021/03/09/jclinpath-2020-206917.short
4100  - http://jcp.bmj.com/content/early/2021/03/09/jclinpath-2020-206917.full
AB  - Aims Vulvar squamous cell carcinoma (VSCC) spreads early and mainly locally via direct expansion into adjacent structures, followed by lymphatic metastasis to the regional lymph nodes (LNs). In the lymphatic metastasis, cancer cells bearing CXCR4 and ACKR3 (CXCR7) receptors are recruited to the LNs that produce the CXCL12 ligand. Our study aimed to assess the role of the CXCR4/ACKR3/CXCL12 axis in VSCC progression.Methods Tumour and LN tissue samples were obtained from 46 patients with VSCC and 51 patients with premalignant vulvar lesions. We assessed CXCR4, ACKR3 and CXCL12 by immunohistochemistry (IHC) in the tissue samples. Additionally, CXCL12 levels were determined by ELISA in the sera of 23 patients with premalignant lesions, 37 with VSCC and 16 healthy volunteers.Results CXCR4 and ACKR3 proteins were virtually absent in vulvar precancers, while in VSCC samples the IHC staining was strong. In the LNs of patients with VSCC, 98% of metastatic cells expressed CXCR4 and 85% expressed ACKR3. Neither CXCR4 nor ACKR3 presence was correlated with tumour human papilloma virus status. Few CXCL12-positive cells were found in the analysed tissue samples, but serum CXCL12 levels were significantly increased in both patients with premalignant vulvar lesions and with VSCC compared with healthy volunteers.Conclusions It appears that during progression and lymphatic spread of VSCC, the CXCR4/ACKR3/CXCL12 axis is activated. Moreover, our data suggest that CXCR4 antagonists merit further attention as a possible therapeutic option in patients with VSCC.