Upregulation of the Tissue Inhibitor of Metalloproteinase-1 Protein Is Associated With Progression of Human Non–Small-Cell Lung Cancer

Aljada, Ibrahim S.; Ramnath, Nithya; Donohue, Kathleen; Harvey, Shashikumar R.; Brooks, John J.; Wiseman, Sam M.; Khoury, Thaer; Loewen, Gregory; Slocum, Harry K.; Anderson, Timothy; Bepler, Gerold; Tan, Dongfeng

doi:10.1200/jco.2004.02.110

Cited by 51 publications

(44 citation statements)

References 48 publications

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“…In our study, the TIMP-1 immunoreactive protein appeared as a diffuse staining in the cytoplasm. This is in line with some previous studies using immunohistochemical methods (37,38).…”

Section: Timp-1 In Head and Neck Squamous Cell Carcinomasupporting

confidence: 93%

“…Elevated levels of circulating TIMP-1 have previously been shown to be associated with poor prognosis in lung, ovarian, transitional cell or colorectal carcinoma, and tissue TIMP-1 has been reported to predict independently shortened survival in multivariate analysis in breast carcinoma (14, 34 -37). Very recently, Aljada et al also published a study on non -small cell lung cancer showing that patients with a tumor showing a high TIMP-1 expression had an increased risk of death compared with patients presenting with a low expression of TIMP-1 (38).…”

Section: Discussionmentioning

confidence: 99%

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Tissue Inhibitor of Matrix Metalloproteinase-1 Is Prognostic in Head and Neck Squamous Cell Carcinoma: Comparison of the Circulating and Tissue Immunoreactive Protein

Ruokolainen¹,

Pääkkö

Turpeenniemi‐Hujanen³

2005

Clinical Cancer Research

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Purpose:Tissue inhibitors of metalloproteinases (TIMP) are capable of inhibiting the matrix metalloproteinases, but they also possess other biological functions. Little is known about the role of TIMP-1in the progression and spreading of cancer cells among patients with head and neck squamous cell carcinoma (HNSCC). In this study, the pretreatment serum levels of TIMP-1or the overexpression of TIMP-1 immunoreactive protein in the primary tumor was correlated to the clinical course in patients with HNSCC. Experimental Design:TheTIMP-1immunoreactive protein was studied in 74 cases representing HNSCC. The tissue immunoreactive protein was evaluated from paraffin-embedded tumor sections in 68 cases using immunohistologic staining with a specific antibody, and in 68 cases the pretreatment serum levels of TIMP-1 were quantitatively measured by ELISA assay. The results were compared with the clinicopathologic factors of the disease and the patients'outcome. Results: A positive correlation was found between the size of the primary tumor (T) and the circulating TIMP-1 level (P = 0.021) or the positive immunoreaction of TIMP-1 in tumor (P = 0.039). The 5-year cause-specific survival was significantly lower in patients presenting with a high serum TIMP-1 level than in those with a low level of TIMP-1 (38% versus 64%, P = 0.034). They also had an unfavorable 5-year relapse-free survival rate (37% versus 56%, respectively). Similarly, the expression of TIMP-1 in tumor was prognostic for shortened survival, the 5-year cumulative relapse-free survival being 42% in patients with a TIMP-1^positive tumor versus 75% in cases with a negative tumor (P = 0.035). TissueTIMP-1positivity also seemed associated to the cause-specific survival (P = 0.075) and to be connected with later lymph node or hematogenic relapses. Conclusions:This study shows for the first time that both circulating and tissueTIMP-1 immunoreactive protein predicts the clinical course and dissemination in HNSCC, suggesting that TIMP-1 might be related to both tumor growth and metastasis in HNSCC.

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“…In our study, the TIMP-1 immunoreactive protein appeared as a diffuse staining in the cytoplasm. This is in line with some previous studies using immunohistochemical methods (37,38).…”

Section: Timp-1 In Head and Neck Squamous Cell Carcinomasupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Tissue Inhibitor of Matrix Metalloproteinase-1 Is Prognostic in Head and Neck Squamous Cell Carcinoma: Comparison of the Circulating and Tissue Immunoreactive Protein

Ruokolainen¹,

Pääkkö

Turpeenniemi‐Hujanen³

2005

Clinical Cancer Research

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“…Although TMA may not be completely representative, it is an efficient way to screen for tissue markers and studies have shown that TMA with 1, 2, and 3 cores will represent about 91%, 96%, and 98%, respectively, compared with whole section studies. [37][38][39][40] Additional full section staining of limited cases showed similar results compared with our microarray results. Compared with our TMA results, the full section results showed no statistical difference in the percentage of positive cases of EAC for IMP3 (TMA, 70%; full section, 77%; Pearson x 2 test, P 5 .86, degrees of freedom of 1) and showed the same mean intensity of expression (mean, 1.27; independent 2-tailed Student t test, P 5 .98) and similar percent of lesional cells with positive staining (TMA mean, 35%; full section mean, 45%; independent 2-tailed Student t test, P 5 .35).…”

Section: Commentsupporting

confidence: 85%

Expression of Insulin-Like Growth Factor II mRNA-Binding Protein 3 in Human Esophageal Adenocarcinoma and Its Precursor Lesions

Wei

Zhou

Peters

et al. 2011

Archives of Pathology &Amp; Laboratory Medicine

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N Context.-Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is an oncofetal protein highly expressed in fetal tissue and malignant tumors but only rarely within adult benign tissues. The expression of IMP3 in esophageal adenocarcinoma (EAC) and its precursor lesions including distinctive type Barrett mucosa (BM, intestinal metaplasia) and esophageal columnar dysplasia (ECD) is largely unknown.Objective.-To characterize the patterns of IMP3 expression in EAC and its precursor lesions.Design.-Samples from 132 cases of EAC, 28 cases of ECD (16 high-grade dysplasia and 12 low-grade dysplasia cases), 28 cases of BM without dysplasia, and 138 cases of nonneoplastic esophageal mucosa without dysplasia or BM within formalin-fixed, paraffin-embedded tissue microarray blocks were examined. Tissues were stained with mouse monoclonal anti-IMP3 antibody. The intensity (1-3+) and percent (0%-100%) of positive cytoplasmic and/or membranous IMP3 staining cells were determined.Results.-Most of EAC cases (93 of 132; 70%) showed cytoplasmic and membranous IMP3 staining. Poorly and moderately differentiated EAC showed statistically significant higher IMP3 expression compared with well-differentiated EAC (P , .001). A subset of ECD cases (7 of 28; 25%) was positive for IMP3, including 3 low-grade dysplasia cases (focal 1+ IMP3 staining) and 4 high-grade dysplasia cases (more diffuse 1-2+ IMP3 staining). No IMP3 staining was observed in any nonneoplastic esophageal mucosa and BM tissues without dysplasia.Conclusions.-This study suggests that IMP3 may play a role in the carcinogenesis of EAC and has diagnostic utility in differentiating neoplastic and nonneoplastic lesions of the esophagus.

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“…Many lines of evidence indicate that TIMP-1 promotes cell proliferation and confers resistance against apoptotic cues (40). However, overexpression of TIMP-1, in general, suppresses cancer progression and metastasis in vivo (17,18), which is also contradictory to the reports that accumulation of TIMP-1 is frequently observed in several types of cancer (19,20) and correlated with poor prognosis (21).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, it is puzzling to find that TIMP-1 is accumulated in tumor tissues (19,20), and the accumulated TIMP-1 is associated with poor prognosis (21).…”

mentioning

confidence: 99%

Overexpression and β-1,6-N-Acetylglucosaminylation-initiated Aberrant Glycosylation of TIMP-1

Kim

Ahn

Song

et al. 2012

Journal of Biological Chemistry

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Background: Early TIMP-1 accumulation may impede cancer progression, and cancer cells need to reduce the antiproteolytic burden. Results: Early overexpression and later aberrant glycosylation of TIMP-1 support tumor progression. Conclusion: Concomitant overexpression of TIMP-1 and GnT-V directs accelerated tumor growth and cancer progression in vivo and in vitro. Significance: An answer to the debate on whether TIMP-1 is pro-or anti-oncogenic is given.

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Upregulation of the Tissue Inhibitor of Metalloproteinase-1 Protein Is Associated With Progression of Human Non–Small-Cell Lung Cancer

Cited by 51 publications

References 48 publications

Tissue Inhibitor of Matrix Metalloproteinase-1 Is Prognostic in Head and Neck Squamous Cell Carcinoma: Comparison of the Circulating and Tissue Immunoreactive Protein

Tissue Inhibitor of Matrix Metalloproteinase-1 Is Prognostic in Head and Neck Squamous Cell Carcinoma: Comparison of the Circulating and Tissue Immunoreactive Protein

Expression of Insulin-Like Growth Factor II mRNA-Binding Protein 3 in Human Esophageal Adenocarcinoma and Its Precursor Lesions

Overexpression and β-1,6-N-Acetylglucosaminylation-initiated Aberrant Glycosylation of TIMP-1

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