Vessel Counts and Expression of Vascular Endothelial Growth Factor as Prognostic Factors in Node-Negative Colon Cancer

Takahashi, Yutaka; Tucker, Susan L.; Kitadai, Yasuhiko; Koura, Aaryan; Bucana, Corazon D.; Cleary, Karen R.; Ellis, Lee M.

doi:10.1001/archsurg.1997.01430290087018

Cited by 288 publications

(192 citation statements)

References 15 publications

(1 reference statement)

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“…In colonic carcinomas there is strong evidence for their predictive value (Weidner et al, 1993;Takahashi et al, 1997;Wong et al, 1999). At first glance, this seems to be contrary to our finding of a uniform microvascular architecture in colorectal carcinomas.…”

Section: Discussioncontrasting

confidence: 99%

3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon

2001

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Summary Despite the significance of tumour neoangiogenesis and the extensive knowledge on the molecular basis of blood vessel formation currently no quantitative data exist on the 3D microvascular architecture in human primary tumours and their precursor lesions. This prompted us to examine the 3D vascular network of normal colon mucosa, adenomas and invasive carcinomas by means of quantitative microvascular corrosion casting. Fresh hemicolectomy specimens from 20 patients undergoing cancer or polyposis coli surgery were used for corrosion casting, factor VIII and VEGF immunostaining. In addition, immunostaining was done on colorectal tissue from 33 patients with metastatic and non-metastatic carcinomas, polyposis coli and adenomas. This first quantitative analysis of intervessel and interbranching distances, branching angles and vessel diameters in human cancer specimens revealed distinct patterns of the microvascular unit in the tumour centre and periphery. Irrespective of the tumour localization and grading all individual tumours displayed qualitatively and quantitatively the same vascular architecture. This gives further evidence for the existence of a tumour type-specific vascular architecture as recently demonstrated for experimental tumours. Metastatic tumours displayed different vascular architectures only within hot spots, in terms of smaller intervascular distances than in non-metastatic tumours. Pre-cancerous lesions have in part virtually the same vascular architecture like invasive carcinomas. Comparison of VEGF immunostaining also suggests that angiogenesis sets in long before the progress towards invasive phenotypes and that the so-called angiogenic switch is more likely a sequence of events.

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Section: Discussioncontrasting

confidence: 99%

3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon

2001

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“…It has been previously reported that patients who present with metastases at the time of surgery for primary colon cancer have higher vessel counts than patients with no evidence of metastases (Takahashi et al, 1997). Thus the high MVD observed in our pushing cohort may be a reflection of advanced disease stage.…”

Section: Discussionmentioning

confidence: 59%

“…The use of CD31 MVD analysis as an indicator of angiogenesis is well described. In this study, MVD analysis was performed using digital image analysis in preference to traditional tumour hotspot MVD measurement, which has been shown to be unreliable in assessing net angiogenic activity (Folkman, 1990;Takahashi et al, 1997;Hlatky et al, 2002;Subarsky and Hill, 2003). Our results proved to be reliable and reproducible on statistical testing.…”

Section: Discussionmentioning

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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“…5,[43][44][45][46][47] Some studies have indicated that VEGF expression is an independent prognostic factor in predicting patient prognosis, 5,[43][44][45] while others have reported no such association. 46 Chung et al 47 also showed that VEGF expression was significantly associated with prognosis and hematogenous spread in colorectal carcinoma. Our study showed that VEGF is a useful prognostic marker by correlating significantly with lymphovascular invasion, lymph node status and pT, although it was not an independent prognostic factor.…”

Section: Discussionmentioning

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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Vessel Counts and Expression of Vascular Endothelial Growth Factor as Prognostic Factors in Node-Negative Colon Cancer

Abstract: Vessel count and expression of VEGF may be useful for predicting distant recurrence in patients with node-negative colon cancer.

Cited by 288 publications

References 15 publications

3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon

3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon

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

Lymphatic microvessel density as prognostic marker in colorectal cancer

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