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High density of peritumoral lymphatic vessels measured by D2-40/podoplanin and LYVE-1 expression in gastric cancer patients: an excellent prognostic indicator or a false friend?

Rudno-Rudzinska J, Kielan W, Grzebieniak Z, Dziegiel P, Donizy P, Mazur G, Knakiewicz M, Frejlich E, Halon A - Gastric Cancer (2012)

Bottom Line: Statistical analysis showed no impact of increased intratumoral or peritumoral LVD on gastric cancer patient survival, irrespective of the protein used to stain lymphatic vessels.Analysis showed that the probability of overall survival was decreased in the cases with enhanced VEGF-D immunoreactivity (P = 0.0045).VEGF-D is the only marker that can be regarded as an unfavorable prognostic indicator for patients with advanced gastric cancer.

View Article: PubMed Central - PubMed

Affiliation: 2nd Department of General and Oncological Surgery, Wroclaw Medical University, Borowska 213, 50-556, Wrocław, Poland, jrr@id.pl.

ABSTRACT

Background: One of the most important prognostic indicators in gastric cancer is the presence of metastases in lymph nodes. Even now, little is known about lymphangiogenesis in neoplastic tissue, and little is also known about the transmission of a neoplastic cell from the tumor mass into a lymphatic vessel.

Methods: This study examined the relationships between the density of lymphatic vessels (LVD) stained immunohistochemically with lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and D2-40 (podoplanin) antibodies, the expression of vascular endothelial growth factor (VEGF)-C/D, selected clinical and pathomorphological factors, and the 5-year overall survival of gastric cancer patients.

Results: Statistical analysis showed no impact of increased intratumoral or peritumoral LVD on gastric cancer patient survival, irrespective of the protein used to stain lymphatic vessels. Analysis showed that the probability of overall survival was decreased in the cases with enhanced VEGF-D immunoreactivity (P = 0.0045).

Conclusion: The study showed that the studied markers cannot be used to determine the required extent of the surgical procedure, as they have no statistically significant correlation with the degree of progression of the cancer, the stage of the disease assessed according to the TNM 5th classification of malignant tumors, clinicopathological features, and patient survival. VEGF-D is the only marker that can be regarded as an unfavorable prognostic indicator for patients with advanced gastric cancer.

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Related in: MedlinePlus

Kaplan–Meier curve for two groups of patients: solid line, VEGF-D expression (Immuno Reactive Score, IRS) = 0; dashed lineIRS = 1–4)
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Fig3: Kaplan–Meier curve for two groups of patients: solid line, VEGF-D expression (Immuno Reactive Score, IRS) = 0; dashed lineIRS = 1–4)

Mentions: A Cox regression analysis has shown no impact of increased intratumoral or peritumoral LVD on GC patient survival, irrespective of the type of markers. A similar relationship was found for VEGF-C protein. However, the study indicated a statistically significant correlation between a high level of VEGF-D and patients’ long-term survival, with a significance of P = 0.0045 (according to Cox regression analysis). Patients were divided into two separate groups: the first consists of patients whose expression of VEGF-D proteins was equal to 0 on the IRS scale (31 patients), whereas the second group included all cases with VEGF-D expression between 1 and 4 on the IRS scale (11 patients). For each group a Kaplan–Meier curve was calculated (Fig. 3). Based on statistical analysis, the survival rate within the first group could be estimated at around 41 %, whereas within the second group the chance for remaining alive is estimated as around 18 %. It is worth pointing out that both curves were tested using the log-rank test with the hypothesis, which considered both groups had identical survival functions. The test’s result (Z = −2.03948, P = 0.0207) forced rejection of the hypothesis. Therefore, we can state that there is a significant difference in survival rate depending on whether the patient has VEGF-D expression equal to 0 or more than 0 (1–4). Based on the calculations, it could be stated that patients with a positive VEGF-D expression level have a chance of surviving treatment more than twofold less than do the patients with IRS equal to 0.Fig. 3


High density of peritumoral lymphatic vessels measured by D2-40/podoplanin and LYVE-1 expression in gastric cancer patients: an excellent prognostic indicator or a false friend?

Rudno-Rudzinska J, Kielan W, Grzebieniak Z, Dziegiel P, Donizy P, Mazur G, Knakiewicz M, Frejlich E, Halon A - Gastric Cancer (2012)

Kaplan–Meier curve for two groups of patients: solid line, VEGF-D expression (Immuno Reactive Score, IRS) = 0; dashed lineIRS = 1–4)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824260&req=5

Fig3: Kaplan–Meier curve for two groups of patients: solid line, VEGF-D expression (Immuno Reactive Score, IRS) = 0; dashed lineIRS = 1–4)
Mentions: A Cox regression analysis has shown no impact of increased intratumoral or peritumoral LVD on GC patient survival, irrespective of the type of markers. A similar relationship was found for VEGF-C protein. However, the study indicated a statistically significant correlation between a high level of VEGF-D and patients’ long-term survival, with a significance of P = 0.0045 (according to Cox regression analysis). Patients were divided into two separate groups: the first consists of patients whose expression of VEGF-D proteins was equal to 0 on the IRS scale (31 patients), whereas the second group included all cases with VEGF-D expression between 1 and 4 on the IRS scale (11 patients). For each group a Kaplan–Meier curve was calculated (Fig. 3). Based on statistical analysis, the survival rate within the first group could be estimated at around 41 %, whereas within the second group the chance for remaining alive is estimated as around 18 %. It is worth pointing out that both curves were tested using the log-rank test with the hypothesis, which considered both groups had identical survival functions. The test’s result (Z = −2.03948, P = 0.0207) forced rejection of the hypothesis. Therefore, we can state that there is a significant difference in survival rate depending on whether the patient has VEGF-D expression equal to 0 or more than 0 (1–4). Based on the calculations, it could be stated that patients with a positive VEGF-D expression level have a chance of surviving treatment more than twofold less than do the patients with IRS equal to 0.Fig. 3

Bottom Line: Statistical analysis showed no impact of increased intratumoral or peritumoral LVD on gastric cancer patient survival, irrespective of the protein used to stain lymphatic vessels.Analysis showed that the probability of overall survival was decreased in the cases with enhanced VEGF-D immunoreactivity (P = 0.0045).VEGF-D is the only marker that can be regarded as an unfavorable prognostic indicator for patients with advanced gastric cancer.

View Article: PubMed Central - PubMed

Affiliation: 2nd Department of General and Oncological Surgery, Wroclaw Medical University, Borowska 213, 50-556, Wrocław, Poland, jrr@id.pl.

ABSTRACT

Background: One of the most important prognostic indicators in gastric cancer is the presence of metastases in lymph nodes. Even now, little is known about lymphangiogenesis in neoplastic tissue, and little is also known about the transmission of a neoplastic cell from the tumor mass into a lymphatic vessel.

Methods: This study examined the relationships between the density of lymphatic vessels (LVD) stained immunohistochemically with lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1) and D2-40 (podoplanin) antibodies, the expression of vascular endothelial growth factor (VEGF)-C/D, selected clinical and pathomorphological factors, and the 5-year overall survival of gastric cancer patients.

Results: Statistical analysis showed no impact of increased intratumoral or peritumoral LVD on gastric cancer patient survival, irrespective of the protein used to stain lymphatic vessels. Analysis showed that the probability of overall survival was decreased in the cases with enhanced VEGF-D immunoreactivity (P = 0.0045).

Conclusion: The study showed that the studied markers cannot be used to determine the required extent of the surgical procedure, as they have no statistically significant correlation with the degree of progression of the cancer, the stage of the disease assessed according to the TNM 5th classification of malignant tumors, clinicopathological features, and patient survival. VEGF-D is the only marker that can be regarded as an unfavorable prognostic indicator for patients with advanced gastric cancer.

Show MeSH
Related in: MedlinePlus