Clinical significance of peritumoral lymphatic vessel density and lymphatic vessel invasion detected by D2-40 immunostaining in FIGO Ib1-IIa squamous cell cervical cancer

Abstract

The clinical significance of lymphangiogenesis in cervical cancer remains controversial. Our aim was to investigate the correlation between lymphangiogenesis, lymphatic vessel invasion (LVI) and tumor metastasis, invasion and prognosis in squamous cell cervical cancer. Paraffin sections of 90 patients with FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) Ib1-IIa squamous cell cervical cancer were stained for immunohistochemistry with a D2-40 monoclonal antibody against the carcinoembryonic antigen M2A. The lymphatic vessel density (LVD) and LVI were measured, and their relationship with the clinicopathological data was analyzed. D2-40-positive lymphatic vessels were found in 75 of the 90 patients (83.3 %). All D2-40-positive vessels were located in peritumoral areas. The mean±SD of the peritumoral LVD was 10.08±4.16. The positive rate of LVI was 32.0 % (24/75). The recurrence rate of patients with LVD >10 (62.1 %, 18/29) was significantly higher than that of patients with LVD ≤10 (34.8 %, 16/46, P = 0.021). The 5-year recurrence-free survival rate of patients with LVD >10 (41.0 %) was significantly lower than that of patients with LVD ≤10 (67.0 %, P = 0.045). Univariate analysis showed that the peritumoral LVD (≤10 vs >10) was correlated with LVI (absent vs present, P = 0.016). The peritumoral LVD and LVI showed no correlation with age, FIGO stage, tumor size, tumor grade, depth of invasion, or pelvic lymph node metastasis (all: P > 0.05). Peritumoral lymphangiogenesis was correlated with the recurrence and recurrence-free survival in patients with squamous cell cervical cancer. Examination of peritumoral LVD in these patients might therefore help to estimate the risk of recurrence.

Improved computer-assisted analysis of the global lymphatic network in human cervical tissues

“…[14][15][16][17][18][19][20][21]36 However, contradictory results were reported by three others groups. 10,23,24 Interestingly, a few years ago, Van der Auwera et al 22 proposed that these discrepancies are caused by a lack of reproducibility when lymphatic vessel density is measured by the conventional optical microscopy (hot spot technique). They highlighted that reliable quantification technique needs to be developed for lymphangiogenesis quantification in human solid tumors.…”

“…22 Consequently, no consensus exists on the potential prognostic value of the tumor lymphatic vasculature profile in cervical cancer. 10,23,24 In order to overcome the major restrictions related to the conventional hot spot approach, we have developed an original semi-automated quantification method based on computerized image analysis of lymphatic vessels on whole slide scanned tissue sections. 25 The present work aims at drawing pathologist's attention on the interest of a global lymphatic vasculature analysis on cancer tissues.…”

Tumor‐associated lymphatic endothelial cell promotes invasion of cervical cancer cells

“…Arrest of growth was observed in the LECs cultured in medium without VEGF- C. To identify the TLECs isolated, two unique molecular markers specific for LECs LYVE-1 and D2-40 were used, eliminating mixing of cells of other types, especially micro vessel endothelial cell which exhibits similar physiological characteristics to LEC. LVD in SCC is an independent predictor for poor patient outcome (11)(12)(13)(14), suggesting implication of LECs in progression of cervical cancer.…”

Remodeling of angiogenesis and lymphangiogenesis in cervical cancer development

“…Подопланин широко используется в качестве гистологического маркера лимфатических сосудов; предполагается, что этот белок играет важную роль в регуляции миграции лимфоэндотелиальных клеток и их адгезии к межклеточному матриксу, в осуществлении их взаимодействий с опухолевыми клетками и, соответственно, в инвазии и метастазировании [109]. Согласно результатам иммуногистохимических исследований, PDPN-позитивные сосуды локализованы преимущественно в перитуморальных зонах РШМ IB-IIA стадий [110], их плотность положительно коррелирует с вероятностью рецидива заболевания. Экспрессия подопланина также регистрируется в самих клетках РШМ на инвазивном фронте опухоли, но не внутри опухолевой массы, её уровень коррелирует с инвазией в лимфатическое пространство и наличием метастазов [111].…”

“…При доброкачественных интраэпителиальных изменениях экспрессия PDPN ограничивается базальным слоем клеток, в образцах РШМ in situ уровень экспрессии существенно увеличивается. Подопланин является важным медиатором гетеротипических клеточных взаимодействий при прогрессии РШМ и может рассматриваться в качестве перспективного прогностического маркера [110,111]. Множество аспектов проблемы РШМ-ассоциированного (лимф)ангиогенеза ещё предстоит исследовать.…”