Peritumoral Lymphatic Vessel Density and Vascular Endothelial Growth Factor C Expression in Early-Stage Squamous Cell Carcinoma of the Uterine Cervix

Gombos, Zoltán; Xu, Xiaowei; Chu, Christina; Zhang, Paul J.; Ács, Géza

doi:10.1158/1078-0432.ccr-05-1238

Cited by 155 publications

(165 citation statements)

References 35 publications

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“…We found that intratumoral lymphatic vessels are present in colon cancer, using D2-40. Similar to previous studies, we found that most of intratumoral lymphatics are small and flattened, 23,32,34 contrasting the widely open lymphatics in peritumoral regions.…”

Section: Discussionsupporting

confidence: 91%

“…30 Another study reported that intratumoral lymphatic microvessel density was higher in cervical squamous cell carcinoma cases with lymph node metastasis than in those cases without metas- tasis, although the difference was not significant. 34 On the other hand, peritumoral lymphatic microvessel counts were approximately the same in patients with or without metastasis. 34 In contrast, others proposed peritumoral lymphatic microvessel counts as a prognostic factor in other tumors.…”

Section: Discussionmentioning

confidence: 92%

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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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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 92%

Lymphatic microvessel density as prognostic marker in colorectal cancer

et al. 2006

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“…A few studies showed that VEGF-C support the entry of cancer cells into peritumoral lymphatic vessels. 7,27 These results suggest that VEGF-C plays a role in the formation of lymph node metastasis without active lymphangiogenesis.…”

Section: Discussionmentioning

confidence: 82%

“…Several studies have shown that peritumoral lymphatic vessels are associated with lymph node metastasis, 8,14,17,18,27,40,41 whereas other studies, only for head and neck squamous cell carcinoma, showed that intratumoral lymphatic vessels, and not peritumoral lymphatic vessel density, are important for lymphatic spreads. 3,14,15 Thus, we first examined the VEGF-C and D2-40 expression in cholangiocarcinoma S Aishima et al intratumoral or peritumoral lymphatic vessel density in intrahepatic cholangiocarcinomas, and detected the following: (1) lymphatic vessel density was much lower in the tumor center than in the tumor periphery; (2) lymphatic vessels in the tumor center were frequently collapsed, whereas peritumoral lymphatic vessels showed open lumen; and (3) lower lymphatic vessel density in the tumor center was significantly correlated with the presence of lymphatic invasion.…”

Section: Discussionmentioning

confidence: 99%

“…[22][23][24][25][26] Some clinical studies have shown a correlation between tumor VEGF-C expression and lymph node metastasis. [27][28][29] Intrahepatic cholangiocarcinoma remains an unfortunate liver tumor with a high mortality rate, because many patients diagnosed with cholangiocarcinoma cannot be offered curative treatment. 30 One of the major hallmark of cholangiocarcinoma is its lymph node metastasis.…”

mentioning

confidence: 99%

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Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma

et al. 2008

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Lymph node metastasis via lymphatic vessels is related with an adverse outcome in many tumors. It is unclear whether lymphatic spread needs the development of the new lymphatic vessels or the expression of lymphangiogenetic factor in intrahepatic cholangiocarcinoma. The aim of this study was to assess the role of lymphangiogenesis, vascular endothelial growth factor-C (VEGF-C) expression, and D2-40-positive myofibroblastic cells for lymphatic spread and patient outcome in 88 cases of intrahepatic cholangiocarcinoma. We also assessed VEGF-C expression in 15 cases of metastatic lymph nodes. There was a significant correlation between lower lymphatic vessel density in the tumor center and positive lymphatic invasion (P ¼ 0.0100). Poorly differentiated cholangiocarcinoma showed higher lymphatic vessel density in the tumor periphery and in the peritumoral area (P ¼ 0.0315 and P ¼ 0.0360, respectively). Lymphatic invasion was observed higher in the peritumoral area (63%, 24/38) and in the tumor periphery (79%, 30/38) than in the tumor center (27%, 9/ 38). There was no significant correlation between the proliferative lymphatic vessels and pathologic features; however, lymphatic invasion was significantly associated with VEGF-C expression (P ¼ 0.0006), and the VEGF-C expression was seen in 12 of 15 cases (80%) of metastatic lymph node. Nodal metastasis was correlated with D2-40-positive myofibroblasts (P ¼ 0.0161). VEGF-C expression was an independent prognostic factor by multivariate survival analysis (P ¼ 0.0131). Our findings suggest that VEGF-C has an important role in lymphatic invasion via the preexisting lymphatic vessels in the tumor margin, and that lymphangiogenesis does not play a direct role in lymphatic metastasis. D2-40-positive myofibroblasts may contribute to lymphatic metastasis.

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Development of a Deep Learning Model to Identify Lymph Node Metastasis on Magnetic Resonance Imaging in Patients With Cervical Cancer

Wang

Zhang

et al. 2020

JAMA Netw Open

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IMPORTANCE Accurate identification of lymph node metastasis preoperatively and noninvasively in patients with cervical cancer can avoid unnecessary surgical intervention and benefit treatment planning. OBJECTIVE To develop a deep learning model using preoperative magnetic resonance imaging for prediction of lymph node metastasis in cervical cancer. DESIGN, SETTING, AND PARTICIPANTS This diagnostic study developed an end-to-end deep learning model to identify lymph node metastasis in cervical cancer using magnetic resonance imaging (MRI). A total of 894 patients with stage IB to IIB cervical cancer who underwent radical hysterectomy and pelvic lymphadenectomy were reviewed. All patients underwent radical hysterectomy and pelvic lymphadenectomy, received pelvic MRI within 2 weeks before the operations, had no concurrent cancers, and received no preoperative treatment. To achieve the optimal model, the diagnostic value of 3 MRI sequences was compared, and the outcomes in the intratumoral and peritumoral regions were explored. To mine tumor information from both image and clinicopathologic levels, a hybrid model was built and its prognostic value was assessed by Kaplan-Meier analysis. The deep learning model and hybrid model were developed on a primary cohort consisting of 338 patients (218 patients from Sun Yat

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Peritumoral Lymphatic Vessel Density and Vascular Endothelial Growth Factor C Expression in Early-Stage Squamous Cell Carcinoma of the Uterine Cervix

Cited by 155 publications

References 35 publications

Lymphatic microvessel density as prognostic marker in colorectal cancer

Lymphatic microvessel density as prognostic marker in colorectal cancer

Lymphatic spread is related to VEGF-C expression and D2-40-positive myofibroblasts in intrahepatic cholangiocarcinoma

Development of a Deep Learning Model to Identify Lymph Node Metastasis on Magnetic Resonance Imaging in Patients With Cervical Cancer

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