Correlation between tumor angiogenesis and invasiveness in thymic epithelial tumors

Tomita, Masaki; Matsuzaki, Yasunori; Edagawa, Masao; Maeda, Masayuki; Shimizu, Tetsuya; Hara, Masaki; Onitsuka, Toshio

doi:10.1067/mtc.2002.124389

Cited by 77 publications

(63 citation statements)

References 25 publications

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“…Secondly, WHO type B2/B3, B3 and TC were analyzed together, which may modify outcome. Regarding the first limitation, this study, compared to others, still comprises a relatively large number of patients with aggressive subtypes of TETs (14)(15)(16)18,19). Fortunately, large international databases have recently been created in order to increase the availability of data of this rare tumor (26).…”

Section: Discussionmentioning

confidence: 99%

“…There are only few studies that have investigated the correlation of immunohistochemical stainings with invasion and metastasis, for example: Ki-67 expression is associated with MFS and invasiveness (13,14). VEGF is more frequently and higher expressed in invasive thymomas (14,15). Podoplanin is more often expressed in higher stages of thymoma and is positive in metastasized tumor cells in lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

“…These molecular alterations may be visible with genomic analysis or immunohistochemical staining. Several studies have investigated the diagnostic relevance of molecular markers, but only few have analyzed the influence on invasion and metastasis (12)(13)(14)(15)(16)(17). Also, many researchers excluded patients with TCs or aggressive forms of thymoma with metastatic spread (4,10,16,18,19).…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value of immunohistochemical markers in malignant thymic epithelial tumors

et al. 2016

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Background: Thymic epithelial tumors (TET) are rare neoplasms with inconsistent treatment strategies.When researching for molecular pathways to find new therapies, the correlation between specific molecular markers and outcome has only rarely been investigated. The aim of this study was to investigate the correlation between survival, metastatic potential and invasiveness of aggressive subtypes of TET and immunohistochemical markers. Methods: Overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) and metastasisfree survival (MFS) of patients with WHO type B2/B3 mixed type thymoma (MT), thymoma type B3 (B3) and thymic carcinoma (TC), undergoing surgery [1998][1999][2000][2001][2002][2003][2004][2005][2006][2007][2008][2009][2010][2011][2012][2013] were determined. Tumor specimens were stained using a tissue microarray (TMA) (CD117, CD5, p63, p40, p21, p27, p53, Bcl-2, Ki67, podoplanin, synaptophysin, PTEN and Pax8). Invasive behavior of primary tumors and the presence of extrathoracic metastases were assessed. Results: We found in 23 patients included into this study (four MT, ten B3, nine TC) that (I) p21 expression in the cytoplasm significantly correlated with a decrease of OS (P=0.016), PFS (P=0.034) and MFS (P=0.005); (II) MFS was significantly shorter when the combination of p21-low p27-low p53-high was present (P=0.029); and (III) nuclear p27 (P=0.042), Ki-67 (P=0.024) and podoplanin (P=0.05) expression correlated with the presence of extrathoracic metastases. Conclusions: The main finding of this study is that cytoplasmic p21 expression negatively influences the outcome of malignant TETs and correlates with metastatic activity. Additionally, selected immunohistochemical markers correlate with the distant metastatic potential of TETs. These results may contribute to the stratification of diagnosis and improvement of treatment strategies for thymic malignancies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prognostic value of immunohistochemical markers in malignant thymic epithelial tumors

et al. 2016

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“…Overall results from EGFR tyrosine kinase inhibitors have been disappointing in patients with thymic malignancies and, at present, these therapies cannot be recommended [38].  VEGF-A, VEGFR-1, and VEGFR-2 are overexpressed in thymoma and TC [40,41] and microvessel density and VEGF expression levels have been shown to correlate with both tumor invasion and clinical stage [42]. However, there are limited data regarding the efficacy of angiogenesis inhibitors in thymic malignnancies.…”

Section: Other Treatment Optionsmentioning

confidence: 99%

Unexpected Dramatic Response of Pretreated Invasive Thymic Malignancies on Pemetrexed-Case Report and Review of Current Treatment Modalities

Raman¹,

Surmont²

2012

OJRD

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Thymomas are rare and usually slowly growing tumors, originating from the epithelial layer of the thymus. Prognosis depends on the extent of invasion of adjacent tissues whereby multimodality treatment including surgery with or without adjuvant chemoradiotherapy is the preferred approach for locally advanced thymomas. For metastatic thymomas, only few chemotherapeutic options are available. We report 2 cases of patients with metastatic thymic malignancies with a dramatic response on pemetrexed treatment. The choice for this antifolate therapy is based upon a small series. Because metastatic thymic neoplasm is a rare disease, large randomised trials are not feasible. Case reports on the treatment of these malignancies are very important and can provide readers with the opportunity to deal with rare diseases.

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“…VEGF-A and VEGFR-1 and -2 are overexpressed in thymomas and thymic carcinomas [121,122]. Micro-vessel density and VEGF expression levels have been shown to correlate with tumour invasion, aggressive histology and clinical stage [123].…”

Section: Targeted Therapiesmentioning

confidence: 99%

Thymic epithelial tumours: from basic principles to individualised treatment strategies

Girard¹

2013

European Respiratory Review

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Thymic epithelial tumours represent a wide range of anatomical, clinical, histological and molecular malignant entities that may be aggressive and difficult to treat. The histopathological classification distinguishes thymomas from thymic carcinomas. Thymomas may be associated with autoimmune disorders.The management of thymic epithelial tumours is a paradigm of co-operation between clinicians, surgeons and pathologists, from establishing the diagnosis to organising the multimodal therapeutic strategy. Surgery is the mainstay of the curative-intent treatment, as complete resection represents the most significantly favourable prognostic factor on overall survival. In case of invasion of intra-thoracic structures and/or dissemination to the pleura and the pericardium, precluding complete resection to be achieved, primary chemotherapy has been used to reduce the tumour burden, possibly allowing subsequent surgery and/or radiotherapy.Novel strategies are needed, especially for refractory, recurrent tumours and thymic carcinomas, which carry a poor prognosis. Personalised approaches are currently being developed, as potentially ''druggable'' molecular targets are emerging from recent integrated genomic analyses. Along with the large variety of questions relative to the treatment strategy, thymic epithelial tumours represent a model of therapeutic implementation and achievement in orphan thoracic oncology, showing how the advent of new results induces new questions, as well as diversifies further clinical research directions and international collaborative initiatives.

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Correlation between tumor angiogenesis and invasiveness in thymic epithelial tumors

Cited by 77 publications

References 25 publications

Prognostic value of immunohistochemical markers in malignant thymic epithelial tumors

Prognostic value of immunohistochemical markers in malignant thymic epithelial tumors

Unexpected Dramatic Response of Pretreated Invasive Thymic Malignancies on Pemetrexed-Case Report and Review of Current Treatment Modalities

Thymic epithelial tumours: from basic principles to individualised treatment strategies

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