Intratumoral Lymphatics and Lymph Node Metastases in Papillary Thyroid Carcinoma

Hall, F. De Havilland; Freeman, Jeremy L.; Sylvia, L.; Jackson, David G.; Beasley, Nigel

doi:10.1001/archotol.129.7.716

Cited by 101 publications

(91 citation statements)

References 25 publications

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“…All of the stained vessels were typically thin-walled and devoid of red blood cells. Consistent with previous reports, 22 most lymph vessels were detected in carcinomas with an invasive margin (Figure 1c), and a few of these vessels were identified within the body of the carcinomas (data not shown). Mean intratumoral lymph vessel density was 4.6/each case, and mean peritumoral lymph vessel density was 13.6/each case.…”

Section: Immunohistochemistrysupporting

confidence: 93%

“…7 An earlier report using human papillary thyroid carcinoma also supported our present observation that the presence of lymphatics in papillary thyroid carcinoma was significantly associated with nodal metastasis. 22 VEGF-D expression is upregulated in a number of other types of tumors. 8,15 In this study, we found that increased VEGF-D expression was correlated with lymph node metastasis in papillary thyroid carcinoma.…”

Section: Discussionmentioning

confidence: 99%

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VEGF-D expression and lymph vessels play an important role for lymph node metastasis in papillary thyroid carcinoma

et al. 2005

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Papillary thyroid carcinoma frequently metastasizes to regional lymph nodes, and lymph node metastasis increases the risk of local regional relapse. Recent evidence suggests that vascular endothelial growth factor-D (VEGF-D) promotes lymphangiogenesis, which in turn promotes lymphatic metastasis. Therefore, the role of VEGF-D messenger RNA transcript levels and VEGF-D immunoreactivity in lymph node metastasis in papillary thyroid carcinoma was investigated. In addition, the role of blood vascular vessel, lymph vessel, and Flt-4-positive vessel densities were studied in relation to their suspected association with lymph node metastasis, and with VEGF-D expression. VEGF-D messenger RNA transcript levels by quantitative real-time reverse transcription-polymerase chain reaction and VEGF-D immunoreactivity by immunohistochemistry in 49 papillary thyroid carcinomas were also studied. This was followed by quantitative immunohistochemical staining for CD34, podoplanin, and Flt-4. Lymph node metastasis was significantly correlated with VEGF-D messenger RNA transcript levels (P ¼ 0.027) and VEGF-D immunoreactivity (P ¼ 0.019). Increased lymph vessel density was also correlated with VEGF-D expression and lymph node metastasis. In conclusion, our findings indicate that VEGF-D expression and increased lymph vessel density may have an important role for lymph node metastasis in papillary thyroid carcinoma.

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Section: Immunohistochemistrysupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

VEGF-D expression and lymph vessels play an important role for lymph node metastasis in papillary thyroid carcinoma

et al. 2005

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“…9 Conversely, other investigators have suggested that lymphangiogenesis (formation of new tumorassociated lymphatics) plays an active role in the metastatic spread. [10][11][12] Previous studies have shown the potential clinical significance of intratumoral lymphatic microvessel density as a prognostic marker, correlating with the extent of tumor spread to regional lymph nodes, 11,13 although others have not demonstrated similar findings. 10,14,15 Previous studies have been limited by the lack of specific lymphatic endothelial markers that could be used to discriminate between lymphatics and blood vessels.…”

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confidence: 99%

Lymphatic microvessel density as prognostic marker in colorectal cancer

et al. 2006

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Lymph node metastases is an important prognostic indicator for disease progression and crucial for therapeutic strategies in the work-up of colorectal carcinoma. In this study, we investigated tumor lymphangiogenesis and vascular endothelial growth factor (VEGF) expression as predictive markers for the risk of lymph node metastasis and their relation to other prognostic parameters in colorectal carcinoma. Resected colorectal carcinomas from 90 patients were examined, including 30 patients without lymph node metastases, 30 with only lymph node metastases, and 30 with liver metastases. Cases were immunostained for CD31, D2-40, and VEGF. Positivity stained microvessels were counted in densely vascular/lymphatic foci (hot spots) at Â 400 field ( ¼ 0.17 mm 2 ). Intensity of staining for VEGF was scored on a two-tiered scale. D2-40 lymphatic microvessel density demonstrated significant correlation with CD31 counts (2079 vs 1876/0.17 mm 2 field, Po0.05) and VEGF expression (Po0.01). VEGF was expressed in 61/90 (67%) cases. D2-40 identified lymphatic tumor invasion in 48/90 patients, which was greater than CD31 (37/90) and hematoxylin and eosin (H&E) (31/90). There was a positive significant correlation of D2-40, CD31 counts, and VEGF expression with the presence of lymphovascular invasion and lymph node metastases (Po0.05). D2-40 lymphatic microvessel density correlated significantly with depth of invasion (pT), positive vascular pedicle lymph nodes and liver metastases (Po0.05). In conclusion, D2-40 lymphatic microvessel density showed prognostic significance with positive correlation with lymphovascular invasion, pT, and metastases to lymph nodes and liver. Immunostaining with D2-40 enhances the detection of lymphatic invasion relative to H&E staining and the endothelial marker, CD31.

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“…There has been debate in the literature as to whether lymphatic vessels exist within tumours (Leu et al, 2000;Nathanson et al, 2000;Padera et al, 2000;Birner et al, 2001;Mandriota et al, 2001;Schoppmann et al, 2001;Skobe et al, 2001;Stacker et al, 2001;Beasley et al, 2002;Dadras et al, 2003;Hall et al, 2003;Maula et al, 2003;Straume et al, 2003;Williams et al, 2003); whether tumours induce lymphangiogenesis (Leu et al, 2000;Nathanson et al, 2000;Sleeman, 2000;Mandriota et al, 2001;Schoppmann et al, 2001;Skobe et al, 2001;Stacker et al, 2001;Beasley et al, 2002;Williams et al, 2003); whether lymphangiogenesis or dilated pre-existing lymphatic vessels increase the probability of lymphatic tumour dissemination (Leu et al, 2000;Padera et al, 2000;Sleeman, 2000;Dadras et al, 2003;Straume et al, 2003;Bono et al, 2004); and whether cancer cells require active intravasation (Hartveit, 1990;Gunningham et al, 2000;Kinoshita et al, 2001;Schoppmann et al, 2001).…”

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confidence: 99%

A quantitative analysis of lymphatic vessels in human breast cancer, based on LYVE-1 immunoreactivity

et al. 2005

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This study was undertaken to determine the highly sensitive method for detecting tumour lymphatic vessels in all the fields of each slide (LV), lymphatic microvessel density (LMVD) and lymphatic vessel invasion (LVI) and to compare them with other prognostic parameters using immunohistochemical staining with polyclonal (PCAB) and monoclonal antibodies (MCAB) to the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), and the pan-endothelial marker factorVIII in a series of 67 human breast cancers. In all LYVE-1-stained sections, LV (some of which contained red blood cells) were frequently found localised in extralobular stroma, dermis, connective tissue stroma and adjacent to artery and vein, but were rare within the intralobular stroma or the tumour body (3/67 cases) or areas of widespread invasion. In contrast small blood vessels were observed in intra-and extralobular stroma in the factor VIII-stained sections. Quantitation of vessel numbers revealed that LYVE-1/PCAB detected a significantly larger number of LV than either H&E or LYVE-1/MCAB (Po0.0001). LYVE-1/PCAB detected LVI in 25/67 cases (37.3%) and their presence was significantly associated with both lymph node metastasis (w 2 ¼ 4.698, P ¼ 0.0248) and unfavourable overall survival (OS) (P ¼ 0.0453), while not relapse-free survival (RFS) (P ¼ 0.2948). LMVD had no influence for RFS and OS (P ¼ 0.4879, P ¼ 0.1463, respectively). Our study demonstrates that immunohistochemistry with LYVE-1/PCAB is a highly sensitive method for detecting tumour LV/LVI in breast cancer and LVI is a useful prognostic indicator for lymphatic tumour dissemination.

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Intratumoral Lymphatics and Lymph Node Metastases in Papillary Thyroid Carcinoma

Abstract: The development of intratumoral lymphatics in well-differentiated papillary thyroid carcinoma appears to be associated with the spread of tumor to regional lymph nodes. The antimetastatic potential of targeting these lymphatics may be of potential therapeutic benefit in the future.

Cited by 101 publications

References 25 publications

VEGF-D expression and lymph vessels play an important role for lymph node metastasis in papillary thyroid carcinoma

VEGF-D expression and lymph vessels play an important role for lymph node metastasis in papillary thyroid carcinoma

Lymphatic microvessel density as prognostic marker in colorectal cancer

A quantitative analysis of lymphatic vessels in human breast cancer, based on LYVE-1 immunoreactivity

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