Alterations in plasminogen activation correlate with epithelial cell dysplasia grading in colorectal adenomas

Protiva, Petr; Sordat, Isabelle; Chaubert, Pascal; Saraga, E.; Trân-Thang, C; Sordat, Bernard; Al, Blum; Dorta, Gian

doi:10.1038/bjc.1998.46

Cited by 5 publications

(6 citation statements)

References 32 publications

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“…Increased expression of uPA and PAI-1 along the adenoma-carcinoma sequence (table 2, 3) is in agreement with Abe et al [13] and Provita et al [29]. In the present study, the number of samples in each stage were not enough for correct use of the ¯2 test, so stages were examined as groups of A/B and C/D and Fisher's exact test was applied.…”

Section: Discussionsupporting

confidence: 74%

Significance of Urokinase-Type Plasminogen Activator and Plasminogen Activator Inhibitor-1 (PAI-1) Expression in Human Colorectal Carcinomas

Papadopoulou¹,

Scorilas²,

Yotis³

et al. 2002

Tumor Biol

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Despite the advances in the medical care of colorectal carcinoma patients, the prognosis has improved only marginally over recent decades. Thus, additional prognostic indicators would be of great clinical value to select patients for adjuvant therapy. In the present study, the antigen levels of urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1, and their immunohistochemical staining were compared in paired colorectal tumor (n = 64) and background colon tissue of the same patients with clinical and pathological staging. The antigen levels, measured with an ELISA method, were found to be significantly higher in cancer tissue (mean 1.92 ng/mg protein for uPA and 7.08 for PAI-1) than in corresponding normal mucosa (0.29 ng/mg protein for uPA and 1.11 ng/mg protein for PAI-1). There was a positive correlation between uPA and PAI-1 antigen levels and clinicopathological parameters such as grade (p < 0.001 and p = 0.01, respectively), while for Dukes’ stage, only PAI-1 correlated positively (p = 0.018). Nodal status correlated positively with uPA but not with PAI-1 antigen levels. Immunohistochemical localization of both antigens was observed mainly in cancer cells and much less in stromal cells. Staining intensity increased from adenoma to adenocarcinoma. The degree of staining was associated with grade, Dukes’ stage and nodal status for uPA (p < 0.001, p = 0.002, p < 0.001, respectively) and only with grade for PAI-1 (p = 0.007).

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Section: Discussionsupporting

confidence: 74%

Significance of Urokinase-Type Plasminogen Activator and Plasminogen Activator Inhibitor-1 (PAI-1) Expression in Human Colorectal Carcinomas

Papadopoulou¹,

Scorilas²,

Yotis³

et al. 2002

Tumor Biol

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“…It has been hypothesized that this correlation may be explained by the capacity of PAI-1 to protect the tumour cells from proteolysis at points of invasion [29]. Interestingly, our previous findings suggested that PAI-1, and not uPA, levels found in adenomas and adjacent mucosae could be indicators of postpolypectomy tumour recurrence [14]. The link between PAI-1 levels, poor patient prognosis and possible adenoma recurrence may reflect, in addition to PAI-1 activity as a uPA inhibitor, the existence of dynamic interactions among cells and ECM components, including signalling events, and possibly taking place at a distance from a premalignant or malignant site.…”

Section: Discussionmentioning

confidence: 89%

“…In human colon adenomas, we and others have previously shown that high levels of certain PA members are associated with the early stages of colonic tumour development [13,14]. It is our understanding that these studies were restricted to comparing values obtained from adenomatous versus adjacent mucosa full tissue extracts.…”

Section: Discussionmentioning

confidence: 98%

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The Plasminogen System in Microdissected Colonic Mucosa Distant from an Isolated Adenoma

Saucy

Bachmann

Peterman³

et al. 2010

Pathol. Oncol. Res.

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In the colon, the urokinase-type plasminogen activator (uPA), its receptor (uPAR), and plasminogen activator inhibitors, PAI-1 and PAI-2, are implicated in the transition from mucosa to adenoma and tumour progression. However, expression in the mucosa adjacent, or distant, to an adenoma has not yet been investigated. Three biopsies from mucosae adjacent (20 cm, ipsilateral) and distant (contralateral) to an isolated tubular adenoma were analysed in 14 patients and 8 controls. Laser microdissection isolated stromal and epithelial crypt components, and quantitative RT-PCR analyses of uPA, uPAR, PAI-1 and PAI-2 mRNA levels were performed. Among controls, no significant differences in the markers were noted. With left colon isolated tubular adenoma, uPA, uPAR, and PAI-2 mRNA levels were significantly increased in the adjacent mucosal stroma compared to epithelial crypt levels (p < 0.05). In right colon adenoma, the mRNA levels of these 3 molecular markers were significantly increased only in the adjacent mucosal stromal samples (p < 0.05). Isolated tubular adenoma in the colon increases significantly the mRNA levels of 3 proteolysis-associated molecular markers in the stromal, but not in the epithelial, components of adjacent mucosa. These results suggest the presence of regional and dynamic interactions in apparently non-involved mucosae.

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“…Some studies on colorectal adenomas were based on tissue extracts 10,11. According to these studies, before the tissues were taken by colonoscopic biopsy or surgery, it was difficult to predict the presence of colorectal adenomas.…”

Section: Introductionmentioning

confidence: 99%

Association between Plasma Levels of Plasminogen Activator Inhibitor-1 and Colorectal Neoplasms

Kim¹,

Yang²,

Lim³

et al. 2013

Gut Liver

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Background/AimsPlasminogen activator inhibitor-1 (PAI-1) is important for tumor growth, Invasion, and metastasis. In this study, we investigated the relationship between plasma levels of PAI-1 and colorectal adenomas.MethodsWe reviewed the medical records of 3,136 subjects who underwent colonoscopy as a screening exam. The subjects were classified into a case group with adenomas (n=990) and a control group (n=2,146). Plasma PAI-1 levels were categorized into three groups based on tertile.ResultsThe plasma levels of PAI-1 were significantly higher in adenoma cases than in controls (p=0.023). The prevalence of colorectal adenomas increased significantly with increasing levels of PAI-1 (p=0.038). In the adenoma group, advanced pathologic features, size, and number of adenomas did not differ among the three groups based on tertiles for plasma PAI-1 levels. Using multivariate analysis, we found that plasma level of PAI-1 was not associated with the risk of colorectal adenomas (p=0.675). Adjusted odds ratios for colorectal adenomas according to increasing plasma levels of PAI-1 were 0.980 (95% confidence interval [CI], 0.768 to 1.251) for the second-highest plasma level and 1.091 (95% CI, 0.898 to 1.326) for the highest level, compared with the lowest levels.ConclusionsThese results suggest that elevated plasma PAI-1 levels are not associated with the risk of colorectal neoplasms.

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Alterations in plasminogen activation correlate with epithelial cell dysplasia grading in colorectal adenomas

Cited by 5 publications

References 32 publications

Significance of Urokinase-Type Plasminogen Activator and Plasminogen Activator Inhibitor-1 (PAI-1) Expression in Human Colorectal Carcinomas

Significance of Urokinase-Type Plasminogen Activator and Plasminogen Activator Inhibitor-1 (PAI-1) Expression in Human Colorectal Carcinomas

The Plasminogen System in Microdissected Colonic Mucosa Distant from an Isolated Adenoma

Association between Plasma Levels of Plasminogen Activator Inhibitor-1 and Colorectal Neoplasms

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