Histopathological predictor for regional lymph node metastasis in gastric cancer

Morita, Hiroshi; Ishikawa, Yukio; Akishima-Fukasawa, Yuri; Ito, Kinji; Akasaka, Yoshikiyo; Nishimura, Chiaki; Igarashi, Yoshinori; Ishii, Toshiharu

doi:10.1007/s00428-008-0717-3

Cited by 15 publications

(8 citation statements)

References 39 publications

(47 reference statements)

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“…The lymphatic system is known to be scarcer than the blood network on the gastric wall [20]. This difference was consistent with the results of two other studies regarding the MVD obtained by markers of the lymphatic and blood endothelium in CG [13,18].…”

Section: Discussionsupporting

confidence: 91%

“…Some authors do not even register the precise definition of the microscopic field area used for counting. Previous series of GC using CD34 found MVD values much lower as compared to our study, but those values were expressed only by number of microvessels per field of 200x or 400x, but not by mm 2 [11,14,18]. Only two other studies show similar values to our MVD results [13,19].…”

Section: Discussionsupporting

confidence: 65%

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Microvessel Density Quantification in Gastric Cancer: Comparing Methods for Standard Measures

Gresta¹

2014

J Cancer Sci Ther

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The quantification of angiogenic and linfangiogenic factors has been explored in an attempt to predict the prognosis of various malignancies. In gastric cancer (GC), a promising parameter is the microvessel density (MVD).Objective: The aim of our study is to evaluate the different methods used for its quantification.Methods: 52 cases of GC were labeled by immunohistochemistry for CD34, CD105 and D2-40. The quantification of the microvasculature was performed for each marker by counting microvessels (mv) in three "hot spots", using three different microscopic magnifications (100x, 200x and 400x). MVD was then calculated by dividing the number of vessels by the microscopic field area (measured in mm 2 ) and compared between the three different evaluations. . We found that MVD obtained in 100x magnification was lower than 200x, which was lower than in 400x. Those differences were statistically significant and occurred in a proportional way for all three markers. MVD obtained for CD34 was higher than for CD105. The MVD for lymphatics obtained by D2-40 was lower than the MVD for CD34 and CD105. Results Conclusion:Our results show that the lack of standardized methods for assessing angiogenesis and lymphangiogenesis in GC can produce variations in the MDV value, impairing the reproducibility of the results and the comparison between different studies and populations. It is necessary to standardize the MVD determination methods to compare results and confirm its prognostic value in GC and in other types of tumors. Material and MethodsThis is a cross-sectional study of a series of cases of primary GC with IHC study. We selected 52 cases of GC retrospectively from the database of the Gastrointestinal Pathology research laboratory from Hospital das Clinicas of Federal University of Minas Gerais. All patients underwent a gastrectomy and lymphadenectomy for GC in the same institution.The IHC study was performed in tumor sections using streptavidinbiotin peroxidase (Dako LSAB ® + System) with CD34, CD105 and D2-40 markers. All slides were pre-treated in a buffer at 98°C in a steamer for 20 minutes for antigen retrieval. Blockage of endogenous peroxidase and avidin protein for 15 minutes each were carried out. The D2-40, CD34 and CD105 primary antibodies were incubated for 30 minutes at room temperature. The slides were revealed with diaminobenzidine. The background staining was performed with hematoxylin. Positive and negative controls were included in all reactions.The quantification of the microvasculature was performed according to the method described by Weidner et al. [1]. The three hot spots were initially detected at lower magnification (40x) and selected in each marker. Those areas were captured and digitized for morphometric image analysis. The microvessel count was performed in the same hot spot area using the following microscopic magnifications: 100x, 200x and 400x. Isolated endothelial cells or groups of cells highlighted by the endothelial markers, with or without lumen, were considered as individual v...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 65%

Microvessel Density Quantification in Gastric Cancer: Comparing Methods for Standard Measures

Gresta¹

2014

J Cancer Sci Ther

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“…Arigami et al 54 showed a correlation between VEGF-C and -D over-expression in primary tumor obtained by RT-PCR and the presence of lymph node micrometastasis in early gastric cancer. These results were confirmed by Morita et al 55 that found a relation between VEGF-C expression and lymph nodes metastases only in early gastric cancer. Kondo et al 56 demonstrated a correlation between positive immnunoreactivity of both VEGF-C and -A and lymph node metastasis in gastric cancer.…”

Section: Vascular Endothelial Growth Factor (Vegf)supporting

confidence: 78%

Clinical and biological markers in gastric cancer update and perspectives

et al. 2010

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Gastric cancer is the second cause of death from cancer worldwide and the only chance to reach better outcomes lays on an early diagnosis. The need for non-invasive, low-cost tests is invoked also in countries in which imaging and endoscopic screening have already showed the ability to improve early diagnosis and overall survival. Genomic medicine could allow a better understanding of regulatory pathways driving the development and growth of gastric cancer and the characterization of specific molecular targets actually stimulate new drug developments. The knowledge of the role of Helicobacter pylori (HP) in gastric tumor pathogenesis has put new insides in the understanding of this peculiar disease and enriched the field of gastric biomarkers.

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“…Vascular endothelial growth factor C (VEGF-C) and its receptor, VEGF receptor 3 (VEGFR-3), have been identified as the principal growth factors and the vital receptor for lymphangiogenesis in a variety of human malignancies, including gastric cancer [1–4]. However, the signaling pathway activated by the interaction between VEGF-C and VEGFR-3 in tumor cells is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Expression and Significances of Contactin-1 in Human Gastric Cancer

et al. 2013

Gastroenterology Research and Practice

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Background. This study aimed at determining the relationship between vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor receptor-3 (VEGFR-3), and contactin-1 (CNTN-1) expression in gastric cancer (GC). Methods. The expression level of CNTN-1 mRNA and CNTN-1 protein of 33 cases was determined using RT-PCR and Western Blot. And 105 cases were immunohistochemically examined for VEGF-C, VEGFR-3, and CNTN-1 expressions. Assessment of lymphatic vessel density (LVD) was also performed by D2-40 immunostaining. Then we analyzed the relationships between VEGF-C, VEGFR-3, and CNTN-1, as well as their correlations with clinicopathologic features, LVD, and survival time. Results. The positivity rate of VEGF-C, VEGFR-3, and CNTN-1 in primary tumor was 56.19%, 64.76%, and 58.09%. The expression of CNTN-1 significantly correlated with VEGF-C (P < 0.001) and VEGFR-3 (P < 0.001). All of them were closely related to TNM stage, lymphatic invasion, and lymph node involvement (P < 0.05). LVD was significantly correlated with VEGF-C (P = 0.001), VEGFR-3 (P = 0.011), and CNTN-1 expression (P < 0.001). VEGF-C, VEGFR-3, and CNTN-1 expression significantly associated with poorer prognosis (P < 0.001, P = 0.034, P = 0.012, resp.). Conclusion. CNTN-1 associated with VEGF-C and VEGFR-3 expression in GC. All of them correlated with lymphatic metastasis, which might play an important role in the lymphatic invasion via lymphangiogenesis pathway in GC.

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Histopathological predictor for regional lymph node metastasis in gastric cancer

Cited by 15 publications

References 39 publications

Microvessel Density Quantification in Gastric Cancer: Comparing Methods for Standard Measures

Microvessel Density Quantification in Gastric Cancer: Comparing Methods for Standard Measures

Clinical and biological markers in gastric cancer update and perspectives

Expression and Significances of Contactin-1 in Human Gastric Cancer

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