RESEARCH PAPER
Metastatic and non-metastatic sentinel inguinofemoral lymph nodes in vulvar cancer show an increased lymphangiogenesis
 
More details
Hide details
1
Department of Gynecology and Oncology, Jagiellonian University Medical College, Krakow, Poland
2
Faculty of Medicine and Health and Medical Science, Andrzej Frycz Modrzewski University, Krakow Poland
3
Department of Pathomorphology, Jagiellonian University Medical College, Krakow, Poland
4
Oncology Centre – M. Skłodowska-Curie Institute, Krakow, Poland
5
Department of Economic and System Analyses, National Institute of Public Health – National Institute of Hygiene, Warsaw, Poland
6
Department of Health Economics and Medical Law, Medical University of Warsaw, Warsaw, Poland
7
Department of Public Health, Faculty of Health Science, Medical University of Warsaw, Warsaw, Poland
8
National Institute of Public Health – National Institute of Hygiene, Warsaw, Poland
CORRESPONDING AUTHOR
Kazimierz Pityński   

Jagiellonian University Department of Gynecology and Oncology
 
KEYWORDS
TOPICS
ABSTRACT
Introduction and objective:
Lymph node involvement is a strong predictor of disease recurrence and patient survival in vulvar cancer. The aim of the study was to evaluate the feasibility of sentinel lymph node (SLN) screening, the incidence of skip metastases, and lymph node lymphangiogenesis.

Material and methods:
Fifty-five patients participated in this prospective, single centre study. A double SLN screening method was employed using radiocolloid (technetium-99 sulfur colloid) and 1.0% Isosulfan Blue. Immunohistochemistry, using a mouse monoclonal antibody against D2–40, was used to evaluate lymphatic vessel density (LVD). All calculations were performed using STATISTICA software v. 10 (StatSoft, USA, 2011); p < 0.05 was considered significant.

Results:
Using both methods of SLN detection, 100% accuracy was achieved, and skip metastases were diagnosed in only one woman (1.82%). Peri-tumour median LVD was significantly increased compared with matched intra-tumour samples (p < 0.001), while median LVD was significantly lower in negative, compared with positive SLN, regardless of whether matched non-SLN were negative (p < 0.001) or positive (p = 0.005). Metastatic SLN exhibited significantly higher median LVD compared with matched negative non-SLN (p = 0.015), while no significant difference in median LVD was detected between positive SLN and matched positive non-SLN. However, negative SLN had a significantly higher median LVD compared with matched negative non-SLN (p = 0.012).

Conclusions:
SLN detection is a safe and feasible procedure in vulvar cancer. In patients without nodular involvement, SLN, compared with non-SLN, exhibited significantly higher median LVD, which may be an indication of its preparation to host metastases, and thus requires further investigation.

 
REFERENCES (29)
1.
Banas T, Pitynski K, Jach R, Knafel A, Ludwin A, Juszczyk G, Nieweglowska D. Primary vulvo-vaginal cancers: Trends in incidence and mortality in Poland (1999–2012). Gynecol Obstet Invest. 2015; 80: 240–245.
 
2.
Maclean AB, Jones RW, Scurry J, Neill S. Vulvar cancer and the need for awareness of precursor lesions. J Low Genit Tract Dis. 2009; 13: 115–117.
 
3.
Covens A, Vella ET, Kennedy EB, Reade CJ, Jimenez W, Le T. Sentinel lymph node biopsy in vulvar cancer: Systematic review, metaanalysis, and guideline recommendations. Gynecol Oncol. 2015; 137: 351–361.
 
4.
Hacker NF, Barlow EL. Sentinel node biopsy in vulvar cancer: A critical appraisal. Asian J Oncol. 2017; 3(1): 5–11.
 
5.
Stacker SA, Williams SP, Karnezis T, Shayan R, Fox SB, Achen MG. Lymphangiogenesis and lymphatic vessel remodelling in cancer. Nat Rev Cancer. 2014; 14: 159–172.
 
6.
Rahmani M, Mohammed S. Breast cancer metastasis and the lymphatic system. Oncol Lett. 2015; 10: 1233–1239.
 
7.
Dieterich LC, Detmar M. Tumour lymphangiogenesis and new drug development. Adv Drug Deliv Rev. 2016; 99: 148–160.
 
8.
Dadras SS, Lange-Asschenfeldt B, Velasco P, Nguyen L, Vora A, Muzikansky A, Jahnke K, Hauschild A, Hirakawa S, Mihm MC, Detmar M. Tumour lymphangiogenesis predicts melanoma metastasis to sentinel lymph nodes. Mod Pathol. 2005; 18: 1232–1242.
 
9.
Van den Eynden GG, Van der Auwera I, Van Laere SJ, Huygelen V, Colpaert CG, van Dam P, Dirix LY, Vermeulen PB, Van Marck EA. Induction of lymphangiogenesis in and around axillary lymph node metastases of patients with breast cancer. Br J Cancer. 2006; 95: 1362–1366.
 
10.
NCCN Clinical Practice Guidelines in Oncology. Uterine Neoplasms. Version 1.2018 – October 13, 2017. Accessed from: https://www.nccn.org/professio.... on 2017-11-20.
 
11.
De Cicco C, Sideri M, Bartolomei M, Grana C, Cremonesi M, Fiorenza M, Maggioni A, Bocciolone L, Mangioni C, Colombo N, Paganelli G. Sentinel node biopsy in early vulvar cancer. Br J Cancer. 2000; 82: 295–299.
 
12.
Sliutz G, Reinthaller A, Lantzsch T, Mende T, Sinzinger H, Kainz C, Koelbl H. Lymphatic mapping of sentinel nodes in early vulvar cancer. Gynecol Oncol. 2002; 84: 449–452.
 
13.
Brincat MR, Muscat Baron Y. Sentinel lymph node biopsy in the management of vulvar carcinoma: An evidence-based insight. Int J Gynecol Cancer. 2017; 27: 1769–1773.
 
14.
Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell 2016; 30: 669–681.
 
15.
Hirakawa S, Kodama S, Kunstfeld R, Kajiya K, Brown LF, Detmar M. VEGF-A induces tumour and sentinel lymph node lymphangiogenesis and promotes lymphatic metastasis. J Exp Med. 2005; 201: 1089–1099.
 
16.
Dadras SS, Paul T, Bertoncini J, Brown LF, Muzikansky A, Jackson DG, Ellwanger U, Garbe C, Mihm MC, Detmar M. Tumour lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival. Am J Pathol. 2003; 162: 1951–1960.
 
17.
Li S, Li Q. Cancer stem cells, lymphangiogenesis, and lymphatic metastasis. Cancer Lett. 2015; 357: 438–447.
 
18.
Ji R. Lymphatic endothelial cells, tumour lymphangiogenesis and metastasis: new insights into intratumoural and peritumoural lymphatics. Cancer Metastasis Rev. 2006; 25: 677–694.
 
19.
Wong SY, Haack H, Crowley D, Barry M, Bronson RT, Hynes RO. Tumour-secreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis. Cancer Res. 2005; 65: 9789–9798.
 
20.
Beasley NJ, Prevo R, Banerji S, Leek RD, Moore J, van Trappen P, Cox G, Harris AL, Jackson DG. Intratumoural lymphangiogenesis and lymph node metastasis in head and neck cancer. Cancer Res. 2002; 62: 1315–1320.
 
21.
Maula SM, Luukkaa M, Grenman R, Jackson D, Jalkanen S, Ristamäki R. Intratumoural lymphatics are essential for the metastatic spread and prognosis in squamous cell carcinomas of the head and neck region. Cancer Res. 2003; 63: 1920–1926.
 
22.
Goes RS, Carvalho JP, Almeida BG, Bacchi CE, Goes JC, Calil MA, Baracat EC, Carvalho FM. Intratumoural lymphatic vessel density in vulvar squamous cell carcinomas: A possible association with favorable prognosis. Int J Gynecol Pathol. 2012; 31:8–14.
 
23.
Christiansen A, Detmar M. Lymphangiogenesis and Cancer. Genes Cancer. 2011; 2: 1146–1158.
 
24.
Ishii K, Chikamatsu, Kakakura K, Miyata M, Furuya N, Masuyama K. Primary tumour induces sentinel lymph node lymphangiogenesis in oral squamous cell carcinoma. Oral Oncol. 2010; 46: 373–378.
 
25.
Jakob C, Aust DE, Liebscher B, Baretton GB, Datta K, Muders MH. Lymphangiogenesis in regional lymph nodes is an independent prognostic marker in rectal cancer patients after neoadjuvant treatment. PLoS ONE. 2011; 611: e27402.
 
26.
Van den Eynden GG, van den Berghe MK, van Dam PJ, Colpaert CG, van Dam P, Dirix LY, Vermeulen PB, Van Marck EA. Increased sentinel lymph node lymphangiogenesis is associated with nonsentinel axillary lymph node involvement in breast cancer patients with a positive sentinel node. Clin Cancer Res. 2007; 13(18): 5391–5397.
 
27.
Wakisaka N, Hasegawa Y, Yoshimoto S, Miura K, Shiotani A, Yokoyama J, Sugasawa M, Moriyama-Kita M, Endo K, Yoshizaki T. Primary tumour-secreted lymphangiogenic factors induce pre-metastatic lymphvascular niche formation at sentinel lymph nodes in oral squamous cell carcinoma. PLoS ONE. 2015; 10: e0144056.
 
28.
Kurahara H, Takao S, Shinchi H, Maemura K, Mataki Y, Sakoda M, Hayashi T, Kuwahata T, Minami K, Ueno S, Natsugoe S. Significance of lymphangiogenesis in primary tumour and draining lymph nodes during lymphatic metastasis of pancreatic head cancer. J Surg Oncol. 2010; 102: 809–815.
 
29.
Cochran AJ, Huang RR, Lee J, Itakura E, Leong SP, Essner R. Tumour-induced immune modulation of sentinel lymph nodes. Nature Rev Immunol. 2006; 6: 659–670.
 
eISSN:1898-2263
ISSN:1232-1966