Lymphatic vessel density and its prognostic value in stage I colorectal carcinoma

Abstract

AimsThe assessment of lymphatic vessel density (LVD) has been suggested as a tool to determine the metastatic risk of neoplasias. On this premise, the authors aimed to verify whether progression risk of stage I colorectal cancer may be related to LVD. The authors also evaluated and correlated vascular endothelial growth factor (VEGF)-A expression with LVD revealed in the same cases in order to investigate its potential lymphangiogenic role in the early stage colorectal cancer.MethodsLVD and VEGF immunoexpression were analysed and compared in series of 29 stage I surgically resected colorectal carcinomas obtained from patients showing disease progression and in a cohort of 23 stage I colorectal cancers from patients with no evidence of disease progression. The prognostic value of LVD and of VEGF expression on the progression-free survival to colorectal cancer was investigated.ResultsA high density of peritumoural lymphatics (P-LVD) was significantly associated with high VEGF expression and disease progression. Moreover, high P-LVD and high VEGF expression were significant negative prognostic parameters associated with a shorter disease-free interval in stage I colorectal cancer.ConclusionsIf our findings are further confirmed in other studies, the assessment of P-LVD on surgical specimens might be used as a tool to identify patients with stage I colorectal cancer at higher risk of progression in order to submit them to adjuvant therapies. Since P-LVD seems to show a VEGF-A mediated regulation in stage I colorectal cancer, therapies targeting this factor might be exploited to reduce lymphangiogenesis and the progression risk of this neoplasia.

Clinical significance of lymph vessel density in T3 colorectal carcinoma

“…The use of a specific lymphatic endothelial marker as D2-40 allows an accurate identification of the lymphatics, avoiding the misinterpretation of blood microvessels as lymphatics. We found a significant difference between PLVD and ILVD with a higher PLVD, in accordance with other reports [23][24][25][26][27][28][29][30][31][32][33] with the exception of the study of Longatto-Filho et al [34]. Moreover, the morphology of lymphatics is different between the two areas, i.e.…”

Quantification of tumour budding, lymphatic vessel density and invasion through image analysis in colorectal cancer

“…LVI was also the only parameter to independently be associated with an adverse effect on disease specific survival. Some studies have shown LVD to be prognostic and associated to poor outcome or LNM [8,38] however others show that no correlation exists [9,39]. LVD assessment is, however, not standardised and most researchers employ various magnifications and numbers of LVD “hot-spots” utilised to create a mean LVD while observer variability has been shown to be strong [9].…”

“…A wealth of original studies, systematic and meta-analysis reviews have been published on the subject of lymphatic vessel invasion (LVI) [5-7], lymphatic vessel density (LVD) [8-10] and tumour budding (TB) [11-15] in CRC prognosis [16,17]. A number of these have concentrated on early stage disease and the ability to utilise histopathological features to predict lymph node metastasis or to stratify patients at high risk of disease recurrence and poor outcome [6,9,16,18-22].…”

Lymphangiogenesis and colorectal cancer

“…However, there are inconsistent results regarding the relationships of LMVD with the clinicopathological parameters of CRC, such as tumor stage, degree of differentiation, and distant metastasis 8-20. We speculate that these discrepancies might be due to the using different antibodies and lacking standardization for the assesment of LMVD.…”

“…In an investigation of 52 stage CRC patients, Barresi et al20 reported that a high density of LMVD was significantly associated with the progression of stage I colorectal carcinoma. Gao et al19 reported that LMVD was reversely related to Dukes’ stage of CRC, it was significantly lower in tumors of Dukes’ stage C + D than in those of Dukes’ stage A + B. Eirik et al25 suggested that lymphangiogenesis is initiated before the tumor reaches stage II by examining LMVD in 18 paired samples of CRC tissues and normal mucosa.…”