Angiogenesis in Malignancies of the Female Genital Tract

Abulafia, Ovadia; Triest, William E.; Sherer, David M.

doi:10.1006/gyno.1998.5152

Cited by 90 publications

(60 citation statements)

References 67 publications

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“…It is the result of predominantly proangiogenic inputs; there is strong evidence of a pivotal role of the hypoxic starting point and VEGF [11]. Many studies analyzed the prognostic role of intratumoral microvessel density (IMD) in ovarian cancer: the results are not homogeneous and the endothelial markers used not the same.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment serum hemoglobin level and a preliminary investigation of intratumoral microvessel density in advanced ovarian cancer

Ferrero¹,

Zola²,

Mazzola³

et al. 2004

Gynecologic Oncology

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Objective. The primary aim of this study was to evaluate the prognostic and predictive value of pretreatment serum hemoglobin level (Hb) in advanced ovarian cancer; second aim was to perform a preliminary investigation of intratumoral microvessel density (IMD).Methods. The influence on survival and response to treatment of several clinico-pathological features, including Hb, was analyzed in 72 patients with advanced ovarian cancer. IMD was assessed in tumor specimens of 25 of the 72 patients to compare three different endothelial markers: anti-FactorVIII, anti-CD31 and anti-CD34. In this subgroup of patients, a preliminary analysis of the prognostic and predictive value of IMD, and its relationship with Hb and other clinico-pathological features, was performed.Results. Hb z 12 g/dl was significantly associated with a better overall survival in univariate analysis ( P = 0.0181) and was the only independent prognostic variable in multivariate analysis ( P = 0.0160). Hb was directly related to progression-free survival ( P = 0.0240) and complete response to treatment ( P = 0.016). In the preliminary investigation of IMD, mean microvessel count did not show any significant difference among the three endothelial markers used, but anti-CD34 revealed a more consistent staining reaction. The relationship between IMD and complete response to treatment was found near to statistical significance ( P = 0.05); Hb and IMD were inversely related (r = À0.47; P = 0.045).Conclusions. Hb has a prognostic and predictive value in advanced ovarian cancer. In our preliminary study, which was performed on a limited number of patients, we found anti-CD34 to be an optimal marker for IMD determination, IMD to be a possible predictive factor of complete response to treatment, and IMD and Hb to be inversely related. D

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Section: Introductionmentioning

confidence: 99%

Pretreatment serum hemoglobin level and a preliminary investigation of intratumoral microvessel density in advanced ovarian cancer

Ferrero¹,

Zola²,

Mazzola³

et al. 2004

Gynecologic Oncology

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“…[1][2][3][4][5] However, lymphatic spread of cancer cells to lymph nodes is an important early event in the metastasis of carcinomas. 6,7 Nodal metastasis is a key factor in the staging, an important prognostic indicator for outcome, and forms the basis of treatment of human cancer.…”

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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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“…[1][2][3][4] Besides being important for tumor progression, angiogenesis plays a crucial role in the dissemination of tumor cells via the blood stream. 5 However, in cervical cancers the earliest feature of disseminated disease is regional lymph node involvement.…”

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confidence: 99%

Low D2-40 immunoreactivity correlates with lymphatic invasion and nodal metastasis in early-stage squamous cell carcinoma of the uterine cervix

Dumoff

Chu

et al. 2005

Modern Pathology

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Lymphatic invasion and nodal metastasis are predictors of shorter disease-free and overall survival in carcinoma of the uterine cervix. The monoclonal antibody D2-40, which reacts with the oncofetal membrane antigen M2A, is a new selective marker for lymphatic endothelium, and has been shown to be useful in identifying the presence of lymphatic invasion in various malignant neoplasms, including cervical carcinoma. However, the reactivity of the tumor cells with D2-40 has not yet been evaluated. In this study, we examined the pattern of D2-40 immunoreactivity in a series of 138 invasive squamous cell carcinomas of the uterine cervix. We correlated the presence and extent of D2-40 immunoreactivity in the tumor cells with various clinicopathologic features, the presence of lymphatic invasion, lymph node metastasis and outcome. Diffuse or focal D2-40 immunoreactivity was present in 17 (12%) and 81 (59%) tumors, respectively, while 40 (29%) tumors showed no immunoreactivity. Lymphatic invasion and nodal metastasis were present in 56 and 29% of tumors, respectively. Tumor emboli within lymphatic spaces and metastatic tumor foci in lymph nodes showed no immunoreactivity in 86 and 80% of the cases, respectively. Lymphatic invasion and nodal metastasis were significantly more common in tumors showing low D2-40 immunoreactivity (Po0.0001 and 0.022, respectively). D2-40 immunoreactivity showed no correlation with any other clinicopathologic features examined, including tumor size, grade and FIGO stage. In univariate analysis low D2-40 immunoreactivity was significantly associated with shorter recurrence-free, but not with overall survival. Our studies suggest that D2-40 immunostaining may serve as a marker for increased risk of lymphatic invasion and tumor recurrence in cervical biopsy material. Further study of the biological function of the M2A antigen may shed some light on the interaction of tumor cells with lymphatics.

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Angiogenesis in Malignancies of the Female Genital Tract

Cited by 90 publications

References 67 publications

Pretreatment serum hemoglobin level and a preliminary investigation of intratumoral microvessel density in advanced ovarian cancer

Pretreatment serum hemoglobin level and a preliminary investigation of intratumoral microvessel density in advanced ovarian cancer

Lymphatic microvessel density as prognostic marker in colorectal cancer

Low D2-40 immunoreactivity correlates with lymphatic invasion and nodal metastasis in early-stage squamous cell carcinoma of the uterine cervix

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