Immunohistochemical co‐localization of lymphatics and blood vessels in oral squamous cell carcinomas

Xuan, Ming; Fang, Yi-Ru; Wato, Masahiro; Hata, Shintaro; Tanaka, Akio

doi:10.1111/j.1600-0714.2005.00316.x

Cited by 29 publications

(27 citation statements)

References 19 publications

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“…Fortunately, several specific antibodies for lymphatics have been found in recent years, which include VGFR-3, podoplanin, Prox1, LYVE-1 and D2-40 monoclonal antibody [9]. The monoclonal antibody D2-40 was initially developed to recognize the M2A antigen, which is an oncofetal glycoprotein expressed by testicular germ cell neoplasm.…”

Section: Discussionmentioning

confidence: 99%

“…Micro vessel density (CD34 positivity) and lymphatic vessel density (D2-40 positivity) in both intratumoural and peritumoural areas were assessed by hot spot method [8,9]. The immunohistochemical positive reaction of D2-40 and CD34 antibodies was evaluated considering its expression in the cytoplasm of lymphatic vessel and blood vessel endothelial cells, respectively [10].…”

Section: Assessmentmentioning

confidence: 99%

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Characterization, Localization and Patterning of Lymphatics and Blood Vessels in Oral Squamous Cell Carcinoma: A Comparative Study Using D2-40 and CD-34 IHC Marker

Pardhe

Bajpai

et al. 2014

JCDR

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Section: Discussionmentioning

confidence: 99%

Section: Assessmentmentioning

confidence: 99%

Characterization, Localization and Patterning of Lymphatics and Blood Vessels in Oral Squamous Cell Carcinoma: A Comparative Study Using D2-40 and CD-34 IHC Marker

Pardhe

Bajpai

et al. 2014

JCDR

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“…Initially it was suggested that only peritumorous lymphatics were involved in the dissemination of neoplastic cells with other authors not finding functional intratumorous lymphatics in various tumours 23,[48][49][50][51] . However, recent research has shown that the latter channels may be present in some carcinomas, including those originating in the head and neck region [52][53][54][55] , thus contributing to the lymphatic spread of neoplastic cells.…”

Section: Discussionmentioning

confidence: 99%

“…The sources of lymphangiogenous factors in tumours are neoplastic cells. Recently, it has been demonstrated, that in some carcinomas, including those originating in the head and neck region, forced VEGF-C and -D expression and density of associated newly formed lymphatic network are significant predictors of nodal involvement and prognosis [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] . Particular histopathologic types of salivary carcinomas show different propensity to nodal metastasis 24 .…”

Section: Introductionmentioning

confidence: 99%

Comparison of lymphatic vessel density and expression of VEGF-C and VEGF-D lymphangiogenic factors in Warthin's tumours and oncocytic adenomas

Hoza¹,

Salzman²,

Bakaj³

et al. 2018

BIOMED PAP

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Objectives.To compare the density of lymphatic vessels and VEGF-C and VEGF-D expression in Warthin's tumours (WTs) and oncocytic adenomas (OCAs). Methods. Twenty three WTs and 13 OCAs of the parotid gland were analyzed. Lymphatic vessels were detected using the D2-40 antibody. For evaluation of the intratumour and peritumour lymphatic vessel density (iLVD and pLVD, respectively) the area of greatest vascularisation (hot spots) was chosen, using a ×40 field, and the number of vessels per square millimeter was counted in a ×200 field. The staining intensity for VEGF-C and VEGF-D immunoreaction in the tumour cells was graded from 0 to 3. Results. The mean iLVD and pLVD values in WTs was 4.7 (range 1-8) and 6.9 (range 3-10), those in the OCAs 1.0 (range 0-3) and 5.8 (range 2-8), respectively. The differences in the iLVD, but not pLVD between the two tumour groups were statistically significant. In both entities, the pLVD markedly outnumbered the iLVD. The intratumour vessels in the WTs were present exclusively in the lymphoid stroma. In the group of 23 WTs, 13 (56.6%), 17 (73.9%) and 10 (43.4%) samples revealed positive VEGF-C, VEGF-D and both immunoreactions, respectively. 10 of 13 (77%) cases revealed VEGF-D immunoreaction and in none of them was the VEGF-C reaction present. Conclusion. The tumours had a comparable high density of peritumorous lymphatic network. However, WTs markedly differed from OCAs in the number of the intratumorous vessels. These were abundant solely in the stroma of WT, while practically lacking in the neoplastic epithelium of the WT and relatively rare in OCAs. We suggest that homeostasis in both entities is mediated mainly by peritumorous lymphatics. The lymphatic drainage in WTs is also fostered exclusively by stromal lymphatics, whereas in stroma poor OCAs by the vessels present in their neoplastic epithelium. We also believe that WTs stimulate proliferation of pre-existing lymphatic capillaries by means of the paracrine secretion of VEGF-C and VEGF-D in the neoplastic as well as reactive stromal cells, while in the OCAs only the latter factor takes part in their lymphangiogenesis.

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“…Distant lymph node metastasis of cancer cells is often due to the involvement of lymphatic vessels (4,5). Despite the occurrence of lymphatic metastasis in those tumors, few studies have focused on the distribution and characteristics of lymphatic vessels in cancers (9,10). Moreover, it remains questionable whether tumor cells induce lymphangiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Localization and characterization of lymphatic vessels in oral and cervical squamous cell carcinoma

Inoue

Roan

Abe

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. Lymph node metastasis is considered a factor in determining the prognosis of squamous cell carcinoma (SCC). Both oral and cervical SCC tumor cells prefer lymph vessels as the route of metastasis. D2-40 is a specific marker of lymphatic endothelial cells. This study clarifies the distribution and characteristics of lymphatic vessels in oral and cervical SCCs. Immunohistochemistry was performed in 20 oral and 20 cervical SCCs (10 non-metastatic and 10 metastatic to lymph nodes) using D2-40, CD31, CD34, CD105 and double staining with D2-40 and keratin. Lymphatic vessel density (LVD) was also determined morphologically. Results showed that lymphatic vessels in both types of SCCs were distributed mainly at the superficial region beneath the epithelium. The LVD in each tumor was significantly higher compared to the corresponding normal mucosa. Moreover, the LVD in lymph node metastasis in each tumor was significantly higher compared to their non-metastatic counterparts. Cancer cell invasion was observed in the lymphatic vessels suggesting the existence of lymph node involvement during metastasis. The new lymphatic vessels that proliferated around the cancer nests in both SCCs have endothelial cell characteristics inferred to be associated with early lymphatic development and initial dissemination of cancer cells. IntroductionThe role of blood vessels in tumor progression and metastasis has been reported in various malignancies, including oral and cervical cancers (1-3). However, the relationship between blood vessels and lymph node metastasis in malignant tumors is largely unknown. Angiogenesis plays a crucial role in hematogenous and lymphatic metastases for which studies have suggested that lesions that entered a higher angiogenic state have an increased probability of metastasis (3,4). However, certain tumors with marked angiogenesis surprisingly had no evidence of metastasis and were associated with a good prognosis (5,6). Thus, an unclear relationship exists among angiogenesis, metastasis and prognosis.Clinically, lymph node metastasis in oral and cervical cancers occurs in 20-30% of cases and is considered a major factor in determining prognosis. Lymphatic spread is more important than other routes. Via this route malignant cells preferentially metastasize in lymph nodes in the cervical region (7). Also, lymphatic vessels are the preferential routes for metastatic spread of most carcinomas that arise in the cervix (8). Distant lymph node metastasis of cancer cells is often due to the involvement of lymphatic vessels (4,5). Despite the occurrence of lymphatic metastasis in those tumors, few studies have focused on the distribution and characteristics of lymphatic vessels in cancers (9,10). Moreover, it remains questionable whether tumor cells induce lymphangiogenesis.Several lymphatic-specific antibodies have been developed (11). Kahn and Marks developed an antibody called D2-40, reported to be effective in detecting lymphatic vessels in formalin-fixed paraffin sections (12). The antibody does not requi...

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Immunohistochemical co‐localization of lymphatics and blood vessels in oral squamous cell carcinomas

Abstract: These results indicate that lymphatic proliferation might be much more extensive in the peritumoral area than intratumoral.

Cited by 29 publications

References 19 publications

Characterization, Localization and Patterning of Lymphatics and Blood Vessels in Oral Squamous Cell Carcinoma: A Comparative Study Using D2-40 and CD-34 IHC Marker

Characterization, Localization and Patterning of Lymphatics and Blood Vessels in Oral Squamous Cell Carcinoma: A Comparative Study Using D2-40 and CD-34 IHC Marker

Comparison of lymphatic vessel density and expression of VEGF-C and VEGF-D lymphangiogenic factors in Warthin's tumours and oncocytic adenomas

Localization and characterization of lymphatic vessels in oral and cervical squamous cell carcinoma

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