Influence of angiogenetic factors and matrix metalloproteinases upon tumour progression in non-small-cell lung cancer

Shou, Yanning; Hirano, Takashi; Gong, Yunbo; Kato, Yasufumi; Yoshida, Kôichi; Ohira, Tetsuya; Ikeda, Norihiko; Konaka, Chimori; Ebihara, Yoshiro; Zhao, Fangyu; Kato, Harubumi

doi:10.1054/bjoc.2001.2137

Cited by 83 publications

(58 citation statements)

References 43 publications

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“…In view of a recent histopathological study of differential expression of MMPs in NSCLC, 14 which reported MMP-9 expression in 36.5% and MMP-9 homogeneous expression in 2.6% of tissue sections, immunohistochemical finding of MMP-9 in 52-65% of specimens might rather be assessed as detection of MMP-9 expression, but may not be considered as detection of homogeneous expression of MMP-9. The high rates of positive immunostaining could result from the cut point of 20% stained cancer cells in both studies 10,11 mentioned above. In contrast, we applied a new immunohistochemical evaluation system that focused exclusively on homogeneous expression of MMP-9.…”

Section: Discussionmentioning

confidence: 83%

“…To our best knowledge, only 2 previous studies investigated the prognostic impact of immunohistochemically detected MMP-9 in NSCLC. 10,11 These studies did not demonstrate an independent prognostic impact of MMP-9 considering all standard prognostic factors included in the international system for staging lung cancer. 6 Furthermore, these 2 previous studies observed MMP-9 expression in 65 or 52% of the patients, respectively.…”

Section: Discussionmentioning

confidence: 89%

“…2). Although Shou et al 11 did not focus on homogeneous MMP-9 expression, they reported an association between MMP-9 expression and unfavorable outcome in univariate log-rank analysis. In their study, MMP-9 expression correlated with the pT-status and the pN-status, suggesting that the observed prognostic value of MMP-9 could result from possible joint effects with the pT-status or pN-status.…”

Section: Discussionmentioning

confidence: 99%

“…First clinical trials investigating the efficacy of MMP-inhibitors in advanced cancer were rather disappointing. 9 Furthermore, previous studies examining the prognostic impact of immunohistochemical detection of MMP-9 in NSCLC 10,11 are discussed controversially because they did not demonstrate an independent prognostic impact of MMP-9 considering all standard prognostic factors included in the international system for staging lung cancer. 6 To clarify the prognostic impact of MMP 9 in operable NSCLC, we applied a new immunohistochemical evaluation system, focusing on homogeneous expression of MMP-9.…”

mentioning

confidence: 99%

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Prognostic impact of matrix metalloproteinase‐9 in operable non‐small cell lung cancer

Sienel¹,

Hellers²,

Morresi‐Hauf³

et al. 2002

Intl Journal of Cancer

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We assessed the clinical impact of MMP-9 expression on long-term survival in patients with operable non-small cell lung cancer (NSCLC). Primary tumors of 143 consecutive patients with NSCLC resected completely and without overt distant metastases (pT1-4, pN0-2, M0, R0) were examined for MMP-9 expression using immunohistochemistry with a polyclonal, affinity-purified rabbit antibody that recognizes both latent and active MMP-9. Immunohistochemical staining of tumor cells was evaluated in comparison to normal bronchiolar epithelium that served as an internal positive control. MMP-9 expression was categorized into negative, <5% tumor cells stained; heterogeneous, >5% and <95% tumor cells stained; and homogeneous, >95% The standard treatment for early stage NSCLC is surgery resulting in a 5-year survival rate of only 50 -60% in Stage I and II. 5,6 A better understanding of the molecular mechanisms of lung cancer progression might help to identify patients at risk for an unfavorable outcome with potential consequences for adjuvant therapy.Penetration of basement membranes and degradation of extracellular matrix are essential steps in the dissemination of tumor cells from primary tumors to distant organs. 7 One group of proteolytic enzymes that has been associated with these abilities is the matrix metalloproteinase family (MMP). Matrix metalloproteinase 9 (MMP-9) (92 kDa Type IV collagenase or gelatinase B) has the potency to degrade gelatin and Type IV collagen, 8 which is a major component of basement membranes. The clinical relevance of MMP 9 in NSCLC remains in discussion. First clinical trials investigating the efficacy of MMP-inhibitors in advanced cancer were rather disappointing. 9 Furthermore, previous studies examining the prognostic impact of immunohistochemical detection of MMP-9 in NSCLC 10,11 are discussed controversially because they did not demonstrate an independent prognostic impact of MMP-9 considering all standard prognostic factors included in the international system for staging lung cancer. 6 To clarify the prognostic impact of MMP 9 in operable NSCLC, we applied a new immunohistochemical evaluation system, focusing on homogeneous expression of MMP-9. The prognostic value was analyzed in relation to established prognostic factors of the TNM-system. Our study shows that the prognostic impact of homogeneous MMP-9 expression remains independent from possible prognostic joint effects of pT-status, pN-status, tumor histology and tumor grading. Because of this independence, MMP-9 may be considered as an interesting target for adjuvant anticancer therapy in operable NSCLC using selective MMP-inhibitors with high specificity for MMP-9. MATERIAL AND METHODS PatientsAfter approval by the ethical committee of the University of Munich and after written informed consent, tissue specimens of 147 consecutive patients with completely resected NSCLC were collected. The tumors were classified according to the international union against cancer (UICC) TNM-classification. 6 The preoperative staging of all patient...

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Prognostic impact of matrix metalloproteinase‐9 in operable non‐small cell lung cancer

Sienel¹,

Hellers²,

Morresi‐Hauf³

et al. 2002

Intl Journal of Cancer

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“…Meyer's hematoxylin was used for counterstaining. 11 All AMeX specimens, which had been prepared during this period, were available for the immunohistochemical investigation, and we evaluated all AMeX specimens except in the Stage IV cases (5 patients).…”

Section: Evaluation Of the Expression Levels Of Rcn And Gst-p In Cultmentioning

confidence: 99%

Identification of postoperative adjuvant chemotherapy responders in non‐small cell lung cancer by novel biomarker

Hirano

Kato

Maeda

et al. 2005

Intl Journal of Cancer

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Cisplatin-based (CDDP-based) adjuvant chemotherapy of nonsmall cell lung cancer (NSCLC) was reported to yield 5-15% improvement in 5-year survival compared to complete resection alone. The importance of information concerning preselection of good responders has become increasingly evident. The purpose of our study is the establishment of a preselection of good responders for CDDP-based adjuvant chemotherapy. We investigated protein expressions comparing intensity between parent strains (H69 and PC14 lung cancer cultured cells) and resistant strains against CDDP using 2-dimensional polyacrylamide gel electrophoresis (2-DE). Immunohistochemically, we evaluated the relationship between protein expression associated with CDDP-resistance and the clinical effects of platinum-based postoperative adjuvant chemotherapy using 126 surgically-resected NCLC materials. We detected 2 kinds of polypeptides that changed expression levels on 2-DE gels. The analyses of the amino acid sequence showed that these polypeptides were reticulocalbin (RCN) and glutathione-Stransferase-p (GST-p). The 2-DE analysis showed decreased expression in RCN and overexpression in GST-p with the acquisition of CDDP-drug resistance. RCN-transfectant of H69 CDDPresistant strain showed intermediate sensitivity between the parent strain and the CDDP-resistant strain. RCN-positive cases showed a statistically significant better disease-free survival only in the cases receiving postoperative platinum-based adjuvant chemotherapy after curative resection (p 5 0.007). In addition, cases that were both RCN-positive and GST-p-negative showed a statistically significantly better outcome (p 5 0.0150). In the cases without postoperative adjuvant chemotherapy no relationship between the outcome and these expressions was seen. The evaluation of RCN and GST-p might provide valuable information concerning postoperatively therapeutic strategy from the standpoint of individualized postoperative therapy. ' 2005 Wiley-Liss, Inc.Key words: reticulocalbin; glutathione-S-transferase-p; cisplatin; individual therapy; non-small cell lung cancer Death due to lung cancer is still increasing in Japan and most Western countries, despite intensive application of various therapeutic strategies, and it is still the leading cause of cancer death in Japan. Though the opportunities of relatively early detection and treatment increase, still more than half of cases of primary lung cancer show advanced stage at the initial definitive diagnoses. Several years ago, we routinely carried out postoperative adjuvant chemotherapy using platinum (cisplatin [CDDP] or carboplatin) for patients with advanced stage non-small cell lung carcinoma (NSCLC) because distant metastasis occurred frequently after surgical treatment only. Clinically favorable outcome was not obtained, however, and the 5-year survival of Stage IIIA was approximately 25%, despite postoperative adjuvant chemotherapy. It had been believed that the efficacy of adjuvant chemotherapy in surgically resected lung cancer was controvers...

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Clinical Relevance of MMP and TIMP Measurements in Cancer Tissue

Bashir

Cao

Zucker

2012

Matrix Proteases in Health and Disease

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Influence of angiogenetic factors and matrix metalloproteinases upon tumour progression in non-small-cell lung cancer

Cited by 83 publications

References 43 publications

Prognostic impact of matrix metalloproteinase‐9 in operable non‐small cell lung cancer

Prognostic impact of matrix metalloproteinase‐9 in operable non‐small cell lung cancer

Identification of postoperative adjuvant chemotherapy responders in non‐small cell lung cancer by novel biomarker

Clinical Relevance of MMP and TIMP Measurements in Cancer Tissue

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