Stromal expression of vascular endothelial growth factor correlates with tumor grade and microvessel density in mammary phyllodes tumors: A multicenter study of 185 cases

Tse, Gary M.; Lui, Pauline Po Yee; Lee, C.Soon; Kung, Fred Y.L.; Scolyer, Richard A.; Law, Ben M. F.; Lau, Thomas K.H.; Karim, Rooshdiya Z.; Putti, Thomas Choudary

doi:10.1016/j.humpath.2004.01.023

Cited by 59 publications

(31 citation statements)

References 20 publications

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“…This finding is consistent with previous studies (Tse et al, 2004;Tezuka et al, 2007). It can be proposed that increased MVD may provide enough oxygen to tumor cells.…”

Section: Discussionsupporting

confidence: 93%

Correlation of Microvessel Density with Nuclear Pleomorphism, Mitotic Count and Vascular Invasion in Breast and Prostate Cancers at Preclinical and Clinical Levels

Muhammadnejad

Muhammadnejad²,

Haddadi³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Tumor angiogenesis correlates with recurrence and appears to be a prognostic factor for both breast and prostate cancers. In the present study, we aimed to investigate the correlation of microvessel density (MVD), a measure of angiogenesis, with nuclear pleomorphism, mitotic count, and vascular invasion in breast and prostate cancers at preclinical and clinical levels. Methods: Samples from xenograft tumors of luminal B breast cancer and prostate adenocarcinoma, established by BT-474 and PC-3 cell lines, respectively, and commensurate human paraffin-embedded blocks were obtained. To determine MVD, specimens were immunostained for CD-34. Nuclear pleomorphism, mitotic count, and vascular invasion were determined using hematoxylin and eosin (H&E)-stained slides. Results: MVD showed significant correlations with nuclear pleomorphism (r=0.68, P=0.03) and vascular invasion (r=0.77, P=0.009) in breast cancer. In prostate cancer, MVD was significantly correlated with nuclear pleomorphism (r=0.75, P=0.013) and mitotic count (r=0.75, P=0.012). In the breast cancer xenograft model, a significant correlation was observed between MVD and vascular invasion (r=0.87, P=0.011). In the prostate cancer xenograft model, MVD was significantly correlated with all three parameters (nuclear pleomorphism, r=0.95, P=0.001; mitotic count, r=0.91, P=0.001; and vascular invasion, r=0.79, P=0.017; respectively). Conclusions: Our results demonstrate that MVD is correlated with nuclear pleomorphism, mitotic count, and vascular invasion at both preclinical and clinical levels. This study therefore supports the predictive value of MVD in breast and prostate cancers.

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“…This finding is consistent with previous studies (Tse et al, 2004;Tezuka et al, 2007). It can be proposed that increased MVD may provide enough oxygen to tumor cells.…”

Section: Discussionsupporting

confidence: 93%

Correlation of Microvessel Density with Nuclear Pleomorphism, Mitotic Count and Vascular Invasion in Breast and Prostate Cancers at Preclinical and Clinical Levels

Muhammadnejad

Muhammadnejad²,

Haddadi³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…The expression of VEGF was found to be predominantly induced in the α-SMA-positive CAFs in a gastric cancer mouse model (Guo et al, 2008) and in a xenograft ovarian cancer model (Spaeth et al, 2009). It has been reported that stromal expression of VEGF is correlated with tumor grade and microvessel density in mammary phyllodes tumors (Tse et al, 2004). In addition, SDF-1 expression is significantly up-regulated in CAFs isolated from breast cancer specimens compared to normal breast fibroblasts (Orimo et al, 2005).…”

Section: Discussionmentioning

confidence: 94%

Ovarian cancer-derived lysophosphatidic acid stimulates secretion of VEGF and stromal cell-derived factor-1α from human mesenchymal stem cells

et al. 2010

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Lysophosphatidic acid (LPA) stimulates growth and invasion of ovarian cancer cells and tumor angiogenesis. Cancer-derived LPA induces differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) to α-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts. Presently, we explored whether cancer-derived LPA regulates secretion of pro-angiogenic factors from hASCs. Conditioned medium (CM) from the OVCAR-3 and SKOV3 ovarian cancer cell lines stimulated secretion angiogenic factors such as stromal-derived factor-1α (SDF-1α) and VEGF from hASCs. Pretreatment with the LPA receptor inhibitor Ki16425 or short hairpin RNA lentiviral silencing of the LPA1 receptor abrogated the cancer CM-stimulated expression of α-SMA, SDF-1, and VEGF from hASCs. LPA induced expression of myocardin and myocardin-related transcription factor-A, transcription factors involved in smooth muscle differentiation, in hASCs. siRNA-mediated depletion of endogenous myocardin and MRTF-A abrogated the expression of α-SMA, but not SDF-1 and VEGF. LPA activated RhoA in hASCs and pretreatment with the Rho kinase inhibitor Y27632 completely abrogated the LPA-induced expression of α-SMA, SDF-1, and VEGF in hASCs. Moreover, LPA-induced α-SMA expression was abrogated by treatment with the ERK inhibitor U0126 or the phosphoinositide-3-kinase inhibitor LY294002, but not the PLC inhibitor U73122. LPA-induced VEGF secretion was inhibited by LY294002, whereas LPA-induced SDF-1 secretion was markedly attenuated by U0126, U73122, and LY294002. These results suggest that cancer-secreted LPA induces differentiation of hASCs to cancer-associated fibroblasts through multiple signaling pathways involving Rho kinase, ERK, PLC, and phosphoinositide-3-kinase.

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“…Studies have shown that p53, Ki67, CD117, 34,35 EGFR, 36 p16, 37 and VEGF 38 (being the lowest in benign PT and the highest in malignant PT) are associated with histologic grades of PT, but none has been proven to be clinically useful. Among these markers, p53 expression and Ki67 index were reported in some studies 39,40 to be significantly associated with disease-free and overall survivals, but other studies 41,42 found no association with recurrence or clinical behavior.…”

Section: Molecular/genetic Featuresmentioning

confidence: 99%

Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates

Zhang

Kleer

2016

Archives of Pathology &Amp; Laboratory Medicine

202

204

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Context.-Phyllodes tumor (PT) of the breast is a rare fibroepithelial neoplasm with risks of local recurrence and uncommon metastases. The classification proposed by the World Health Organization for PTs into benign, borderline, and malignant is based on a combination of several histologic features. The differential diagnosis between PT and fibroadenoma and the histologic grading of PT remain challenging. In addition, the molecular pathogenesis of PT is largely unknown.Objective.-To provide an updated overview of pathologic features, diagnostic terminology, and molecular alterations of PT.Data Sources.-Current English literature related to PT of the breast.Conclusions.-Phyllodes tumor shows a wide spectrum of morphology. There are no clearly distinct boundaries between PT and fibroadenoma. Strict histologic assessment of a combination of histologic features with classification can help to achieve the correct diagnosis and provide useful clinical information. The genomic landscapes of PT generated from genomic sequencing provide insights into the molecular pathogenesis of PT and help to improve diagnostic accuracy and identify potential drug targets in malignant PT.

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Stromal expression of vascular endothelial growth factor correlates with tumor grade and microvessel density in mammary phyllodes tumors: A multicenter study of 185 cases

Cited by 59 publications

References 20 publications

Correlation of Microvessel Density with Nuclear Pleomorphism, Mitotic Count and Vascular Invasion in Breast and Prostate Cancers at Preclinical and Clinical Levels

Correlation of Microvessel Density with Nuclear Pleomorphism, Mitotic Count and Vascular Invasion in Breast and Prostate Cancers at Preclinical and Clinical Levels

Ovarian cancer-derived lysophosphatidic acid stimulates secretion of VEGF and stromal cell-derived factor-1α from human mesenchymal stem cells

Phyllodes Tumor of the Breast: Histopathologic Features, Differential Diagnosis, and Molecular/Genetic Updates

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