Clinicopathologic and prognostic significance of matrilysin expression at the invasive front in human colorectal cancers

Adachi, Yasushi; Yamamoto, Hiroyuki; Itoh, Fumio; Arimura, Yoshiaki; Nishi, Motoi; Endo, Takao; Imai, Kohzoh

doi:10.1002/1097-0215(20010920)95:5<290::aid-ijc1050>3.0.co;2-i

Cited by 97 publications

(109 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[28][29][30][31][32][33] Tumor budding is at least in part driven by the wnt signaling pathway as attested by the fact that nuclear b-catenin accumulates in the nuclei in tumor buds (dedifferentiated cancer cells) at the invasive tumor border. [34][35][36][37] In the present study, nuclear pERK expression was correlated with increasing RHAMM expression in MMR proficient (P ¼ 0.012) and with complete RHAMM expression in presumed Lynch syndrome (P ¼ 0.03), whereas an association was not found in MLH1-negative CRC. This finding leads to the hypothesis that pERK is involved in the mechanism of tumor progression of MMR-proficient CRC and Lynch syndrome by interacting with the wnt signaling pathway and RHAMM: (1) KRAS mutation is found in approximately 35% of unselected CRCs, whereas it is mutated at a particularly low frequency in sporadic MSI-H cancers.…”

Section: Discussionmentioning

confidence: 66%

Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer

et al. 2006

View full text Add to dashboard Cite

RHAMM, a member of the microtubule-associated protein family that interacts with the mitogen-activated protein kinase pathway, is associated with tumor progression, aggressive disease and shortened survival in several tumor types. This study aimed to determine the prognostic value of RHAMM in colorectal cancer (CRC). A series of 1420 unselected, nonconsecutive CRC resections were subdivided into three groups: (1) DNA mismatch repair (MMR)-proficient, (2) MLH1 negative and (3) presumed Lynch syndrome. Immunohistochemical analysis of RHAMM expression (0 vs 40%), increasing expression (increasing percentage positivity) and complete expression (100 vs o100%) was performed using tissue microarray technique and the results were correlated with clinicopathological parameters. Fifty-seven tissue samples of normal colonic mucosa were included as a control group. In a univariate analysis increasing and complete expression of RHAMM were associated with higher N stage (P ¼ 0.023 and 0.021) and worse survival (Po0.0001) in MMR-proficient CRC. Complete expression of RHAMM was associated with worse survival in presumed Lynch syndrome (P ¼ 0.016). In MLH1-negative CRC there was no association between RHAMM expression and the clinicopathological features. In a multivariate analysis, increasing RHAMM expression was an independent adverse prognostic factor in MMR-proficient CRC (Po0.0001) and complete expression in MMR-proficient CRC and presumed Lynch syndrome (Po0.0001 and P ¼ 0.031, respectively). Nuclear pERK expression was associated with increasing RHAMM expression in MMR-proficient CRC (P ¼ 0.012) and with complete RHAMM expression in presumed HNPCC (P ¼ 0.03). Increasing and complete RHAMM expressions are independent adverse prognostic factors in MMR-proficient CRC and presumed Lynch syndrome.

show abstract

Section: Discussionmentioning

confidence: 66%

Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Matrix metalloproteinase-1 reactivity was found to be associated with poor outcome in patients with oesophageal (Murray et al, 1998) and CRC (Murray et al, 1996), whereas MMP-9 immunoreactivity correlated with a markedly poorer outcome in patients with SCC of the head and neck (5-year cause specific survival of 45% in MMP-9-positive tumours vs 92% in MMP-9 negative cases) (Ruokolainen et al, 2004). Matrix metalloproteinase-7 positively correlated with depth of invasion, lymph node metastasis, lymphatic invasion, tumour stage, and poorer outcome in patients with CRC (Adachi et al, 2001). Similarly, abundant MMP-11 (Chenard et al, 1996) and MMP-2 (Talvensaari-Mattila et al, 2003) immunoreactivity in tissue from patients with breast cancer corresponded to a shorter disease-free survival and poorer overall survival.…”

Section: Discussionmentioning

confidence: 99%

“…Despite this literature linking enhanced MMP production with poorer outcome for patients with cancer, the majority of these studies have been at best semi-quantitative and are a measure of expression at a single time point over the course of malignant progression (Chenard et al, 1996;Murray et al, 1996Murray et al, , 1998Adachi et al, 2001;Papadopoulou et al, 2001;Yorioka et al, 2002;Talvensaari-Mattila et al, 2003;Roeb et al, 2004;Ruokolainen et al, 2004). The discovery of polymorphisms in MMP promoters that alter gene expression has revealed strong associations between these genetic variants and increased susceptibility to the development of malignancies and other diseases (Henney et al, 2000;Ye, 2000).…”

Section: Discussionmentioning

confidence: 99%

The collagenase-1 (MMP-1) gene promoter polymorphism - 1607/2G is associated with favourable prognosis in patients with colorectal cancer

et al. 2007

View full text Add to dashboard Cite

Matrix metalloproteinase (MMP) overexpression has been implicated in the pathogenesis of colorectal carcinoma (CRC). Accumulating evidence suggests that MMP promoter single nucleotide polymorphisms (SNPs) effecting gene transcription are associated with enhanced susceptibility for the development of malignant disease, increased tumour invasiveness and poor patient survival. The aim of the current investigation was to determine whether such associations exist in a large CRC patient/control study population. Using an allelic discrimination real-time polymerase chain reaction, polymorphisms in the MMP-1, MMP-2 and MMP-3 gene promoters (À1607, À1306, and À1612 bp, respectively) were assessed in normal blood mononuclear cells from patients with CRC (n ¼ 503) and control subjects (n ¼ 471). Genotypes corresponding to each MMP SNP were correlated with tumour characteristics and clinical outcome. The frequency of each genotype was not statistically different between patients and control subjects and no significant differences were noted between the genotypes and tumour characteristics for the three MMP SNPs. CRC patients with the 2G/2G genotype for the MMP-1 SNP had significantly better 5-year survival compared to patients with a 1G allele (Po0.05). Our results demonstrate that CRC patients with a 2G/2G genotype in the MMP-1 gene promoter SNP have a favourable prognosis. Although our results were unexpected, given that this genotype is associated with enhanced MMP-1 transcriptional activity, they are consistent with recent data highlighting the anti-tumorigenic properties of MMPs.

show abstract

“…This immunohistochemical pattern was most pronounced at the invasive front, an area of the tumor that is particularly active in invasion and metastasis. [25][26][27] The correlation between intensely staining inflammatory infiltration and intensely staining tumor cells at the invasive front suggests an interaction, between inflammatory and tumor cells, which increases matrix metalloproteinase-2 expression and promotes tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Metalloproteinase-2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas

2004

View full text Add to dashboard Cite

Matrix metalloproteinases compose a family of enzymes involved in degradation of the extracellular matrix. Tumor cells must penetrate the basement membrane and traverse the extracellular matrix in order to invade surrounding structures and metastasize to distant sites. Gelatinases, particularly gelatinase A (matrix metalloproteinase-2), demonstrate degradative activity against components of the basement membrane and may be involved in the progression of in situ squamous cell carcinoma lesions. Matrix metalloproteinase-2 overexpression has been correlated with tumor invasiveness and metastasis in a wide variety of cancer types, including squamous cell carcinoma arising on mucous membranes. However, correlation between matrix metalloproteinase-2 overexpression and the spread and prognosis of cutaneous squamous cell carcinoma has not been characterized in the literature at present. In this study, we used immunohistochemical techniques to examine the expression of matrix metalloproteinase-2 in 10 actinic keratosis, 15 in situ, 13 invasive, 13 primary (with documented metastatic disease), 11 metastatic, and 8 recurrent squamous cell carcinoma cases. We found that while the average staining intensity (scale 0-3 þ , 3 þ being strongest) of actinic keratosis and in situ lesions was not statistically significant (0.87-1.3 and 0.75-1.4, respectively), the average staining intensity of invasive squamous cell carcinomas (1.6-2.5) was significantly greater than that of actinic keratosis and in situ lesions. Likewise, while the average staining intensity of primary squamous cell carcinomas and metastatic squamous cell carcinomas was not found to be statistically significant (3.1-3.5 and 3.1-3.8, respectively), the average staining intensity of these lesions was significantly higher than that of invasive lesions. We also found that the intensity of matrix metalloproteinase-2 staining correlates with cellular atypia, inflammation, neovascularization, and the invasive tumor front, as well as tumor aggressiveness, and may play a role in the pathogenesis, invasion, and metastasis of cutaneous squamous cell carcinoma.

show abstract

Clinicopathologic and prognostic significance of matrilysin expression at the invasive front in human colorectal cancers

Cited by 97 publications

References 25 publications

Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer

Overexpression of the receptor for hyaluronic acid mediated motility is an independent adverse prognostic factor in colorectal cancer

The collagenase-1 (MMP-1) gene promoter polymorphism - 1607/2G is associated with favourable prognosis in patients with colorectal cancer

Metalloproteinase-2 expression correlates with aggressiveness of cutaneous squamous cell carcinomas

Contact Info

Product

Resources

About