High vascularity in the peripheral region of non-small cell lung cancer tissue is associated with tumor progression

Ushijima, Chie; Tsukamoto, Shuntaro; Yamazaki, Koji; Yoshino, Ichiro; Sugio, Kenji; Sugimachi, Keizō

doi:10.1016/s0169-5002(01)00246-x

Cited by 68 publications

(46 citation statements)

References 28 publications

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“…Its localization at the endothelial cell junctions suggests an important role in transendothelial cellular migration (Zocchi et al 1996). CD31 and Factor VIII-related antigen are both commonly used endothelial markers for quantifying angiogenesis by calculation of Microvessel Density (MVD) (Weidner 1995, Fox 1997, Ushijima et al 2001, Norrby and Ridell 2003. The quantification of vascularity in tissue sections can be influenced greatly by variations in methodology and one of the most crucial factors is the use of AR in the immunohistochemical staining process.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemistry in the evaluation of neovascularization in tumor xenografts

Wang¹,

Stockard²,

Harkins

et al. 2008

Biotechnic & Histochemistry

141

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Angiogenesis, or neovascularization, is known to play an important role in the neoplastic progression leading to metastasis. CD31 or Factor VIII-related antigen (F VIII RAg) immunohistochemistry (IHC), is widely used in experimental studies quantifing tumor neovascularization in immunocompromised animal models implanted with transformed human cell lines. Quantification, however, can be affected extensively by variations in the methodology used to measure vascularization including antibody selection, pretreatment with antigen retrieval and evaluation techniques. To examine this further, we examined the microvessel density and the intensity of microvascular staining among five different human tumor xenografts and a mouse syngeneic tumor using anti-CD31 and F VIII RAg IHC staining. Different antigen retrieval methods also were evaluated. Maximal retrieval of CD31 was achieved using 0.5 M Tris (pH 10) buffer, while maximum retrieval of F VIII RAg was achieved using 0.05% pepsin treatment of tissue sections. For each optimized retrieval condition, compared to F VIII RAg, anti-CD31 highlighted small vessels better. Furthermore, the microvessel density of CD31 was significantly greater than that of F VIII RAg decorated vessels (p < 0.001). The choice of antibody and antigen retrieval method has a significant affect on immunohistochemical findings when studying angiogenesis. One also must use caution when comparing studies in the literature that use different techniques and reagents.

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Section: Discussionmentioning

confidence: 99%

Immunohistochemistry in the evaluation of neovascularization in tumor xenografts

Wang¹,

Stockard²,

Harkins

et al. 2008

Biotechnic & Histochemistry

141

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“…However, several studies suggest that angiogenesis has little or no predictive value [12,13], although this may reflect methodologic differences, such as the use of different monoclonal antibodies [12]. In a study of the significance of the various VEGF isoforms in NSCLC, Yuan et al reported that a high VEGF-189 level correlated with high 20 Bevacizumab in NSCLC [15]. A similar correlation between poor prognosis and localized elevated MVD at the advancing front of NSCLC tumors, accompanied by increased localized staining of VEGF and its receptor, was also reported by Koukourakis et al [16].…”

Section: Why Target Vascular Endothelial Growth Factor In Lung Cancer?mentioning

confidence: 99%

Non-Small Cell Lung Cancer and Antiangiogenic Therapy: What Can Be Expected of Bevacizumab?

Herbst

Sandler

2004

The Oncologist

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There is an urgent need for new therapies to treat nonsmall cell lung cancer (NSCLC), as progress with current chemotherapy regimens has been limited. The roles of vascular endothelial growth factor (VEGF) in promoting tumor angiogenesis, maintaining existing vasculature, and contributing to resistance to traditional therapies, together with its negative prognostic significance in NSCLC, make it an appropriate target for therapy. Bevacizumab (Avastin TM ; Genentech Inc., South San Fransisco, CA), a monoclonal antibody directed against VEGF, has shown promise in treating a number of different cancers. In a recent phase II trial in patients with advanced metastatic NSCLC, the addition of bevacizumab to standard carboplatin/paclitaxel chemotherapy produced a significantly longer time to progression (32.1 versus 18.4 weeks) and greater response rate (31% versus 19% [not significant]) than chemotherapy alone. In the subset of patients with nonsquamous histologies, response rates and survival were further enhanced, with a mean survival time of 17.9 months versus 12.3 months with chemotherapy alone.Bevacizumab was generally well tolerated and did not appear to increase the incidences or severities of the nausea/vomiting, neuropathy, and renal toxicity that are typically associated with carboplatin/paclitaxel chemotherapy. Adverse events in phase I and II studies included hypertension, thrombosis, proteinuria (with occasional nephrotic syndrome), and epistaxis. Serious tumor-related bleeding episodes (hemoptysis/hematemesis) appear to be the main safety concern in patients with NSCLC, with squamous cell histology as a possible risk factor.Further work is needed to identify the best way to use bevacizumab in NSCLC, including use in combination with other biologic agents and in the adjuvant setting. The Oncologist 2004;9(suppl 1):19-26 The Oncologist 2004;9(suppl 1):19-26 www.TheOncologist.comCorrespondence: Roy S. Herbst, M.D., M.D. Anderson Cancer Center, Department of Head and Neck Medical Oncology, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. Telephone: 713-792-6363; Fax: 713-796-8655; e-mail: rherbst@mdanderson.org Received November 25, 2003; accepted for publication January 15, 2004. ©AlphaMed Press 1083-7159/2004 The Oncologist ® LEARNING OBJECTIVESAfter completing this course, the reader will be able to:1. Identify the role of angiogenesis in non-small cell lung cancer (NSCLC).2. Explain the role of bevacizumab in apparently producing greater response, time to progression, and overall survival rates in a randomized phase II trial comparing carboplatin, paclitaxel, and bevacizumab with carboplatin and paclitaxel without bevacizumab and the limitations of this interpretation.3. Define the main toxicity concerns with the use of bevacizumab in the treatment of NSCLC.Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com CME CMEThis material is protected by U.S. Copyright law. Unauthorized reproduction is prohibited. For reprints contact: Repr...

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“…The assessment of microvessel density (MVD) is frequently used to quantify angiogenesis in archival tissue (Hlatky et al, 2002), although its use as a prognostic indictor is controversial. In breast cancer (Uzzan et al, 2004), non-small cell lung carcinoma (Ushijima et al, 2001) and melanoma (Ribatti et al, 2003), a high MVD is associated with poor outcome. In CRC, a high MVD has been shown to predict disease recurrence and survival in some studies (Saclarides et al, 1994;Tanigawa et al, 1997), whereas other studies have shown an association between high MVD and improved survival (Prall et al, 2003) or have concluded that MVD failed to provide additional prognostic information (Cianchi et al, 2002).…”

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confidence: 99%

The influence of invasive growth pattern and microvessel density on prognosis in colorectal cancer and colorectal liver metastases

et al. 2007

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The nature of the invasive growth pattern and microvessel density (MVD) have been suggested to be predictors of prognosis in primary colorectal cancer (CRC) and colorectal liver metastases. The purpose of the present study was to determine whether these two histological features were interrelated and to assess their relative influence on disease recurrence and survival following surgical resection. Archival tissue was retrieved from 55 patients who had undergone surgical resection for primary CRC and matching liver metastases. The nature of the invasive margin was determined by haematoxylin and eosin (H&E) histochemistry. Microvessel density was visualised using immunohistochemical detection of CD31 antigen and quantified using image capture computer software. Clinical details and outcome data were retrieved by case note review and collated with invasive margin and MVD data in a statistical database. Primary CRCs with a pushing margin tended to form capsulated liver metastases (Po0.001) and had a significantly better disease-free survival than the infiltrative margin tumours (log rank P ¼ 0.01). Primary cancers with a high MVD tended to form high MVD liver metastases (P ¼ 0.007). Microvessel density was a significant predictor of disease recurrence in primary CRCs (P ¼ 0.006), but not liver metastases. These results suggest that primary CRCs and their liver metastases show common histological features. This may reflect common mechanisms underlying the tumour -host interaction.

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High vascularity in the peripheral region of non-small cell lung cancer tissue is associated with tumor progression

Cited by 68 publications

References 28 publications

Immunohistochemistry in the evaluation of neovascularization in tumor xenografts

Immunohistochemistry in the evaluation of neovascularization in tumor xenografts

Non-Small Cell Lung Cancer and Antiangiogenic Therapy: What Can Be Expected of Bevacizumab?

The influence of invasive growth pattern and microvessel density on prognosis in colorectal cancer and colorectal liver metastases

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