Alterations of Gene Expression in Human Colorectal Cancer

Steele, Glenn; Davis, Samuel; Yow, Hsiukang; Wong, Jau Min; Rivers, Elissa N.; Summerhayes, Ian C.; Ravikumar, T. S.; Chen, Lan Bo

doi:10.1001/archsurg.1990.01410160079018

Cited by 10 publications

(3 citation statements)

References 5 publications

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“…AEC kit (Nichirei, Japan) for MT expression and DAB kit (Nichirei, Japan) for PCNA expression were used to visualize the sites of HRP. As positive control for MT staining, normal human colonic mucosa, which was already reported to express MT (Mulder et al, 1990;Steele et al, 1990) was used. To ensure consistency of PCNA staining, a known positive control oesophageal carcinoma was included in each run (Kinugasa et al, 1996).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Metallothionein expression correlates with metastatic and proliferative potential in squamous cell carcinoma of the oesophagus

et al. 1999

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Squamous cell carcinoma (SCC) of the oesophagus is well recognized for its aggressive biological behaviour, in respect of local infiltration and metastases to regional lymph nodes and distant organs (Orrigner, 1997). Extra-oesophageal tumour spread is present in 70% of cases at the time of diagnosis, and the 5-year survival is only 3% when lymph node metastases are present, compared with 42% in lymph node negative patients (Orrigner, 1997). Patients with distant metastasis also have a poor prognosis, with a 5-year survival rate of 5% or less (Mandard et al, 1984;Orrigner, 1997).Metastasis is a multistep process involving complex associations of tumour cells with host cells or with matrix (Stracke and Liotta, 1995). Recently, genetic mechanisms underlying metastasis and pathogenesis of oesophageal SCC have been explored in several studies: int-2/hst-1 co-amplification correlated with high incidence of metastasis in distant organs (Kitagawa et al, 1991), loss of heterozygosity of the DCC gene associated with the degree of lymph node metastasis (Miyake et al, 1994), and mutation of the p53 gene in the pathogenesis (Hollstein et al, 1990;Meltzer et al, 1991) of SCC. However, there are only a limited number of reports on the prognostic indicators for invasion and metastasis of oesophageal SCC.Metallothioneins (MTs) have been described in most vertebrate and invertebrate species as low molecular weight proteins. Overexpression of MT was described in a variety of human tumours, in relation to different stages of tumour development and progression (Jasani and Schmid, 1997). MT was considered as a potential prognostic marker in invasive ductal carcinoma of the breast by Schmid et al (1993) and others (Fresno et al, 1993;Goulding et al, 1995, Oyama et al, 1996. In skin carcinoma (Zelger et al, 1994), melanoma (Zelger et al, 1993), cervical carcinoma (Lim et al, 1996) and pancreatic carcinoma (Ohshio et al, 1996), MT overexpression appears to be predominantly associated with more advanced, highly malingant tumours. To the contrary, Öfner et al (1994) reported that MT overexpression in colorectal carcinoma was associated with better clinical outcome and tumour stages. Therefore, MT overexpression may be paradoxically associated in some tumours with better clinical outcome.Tumour MT level also has been reported to correlate with resistance to anticancer reagents (Kelley et al, 1988;Kasahara et al, 1991;Chin et al, 1993;Kondo et al, 1995;Hishikawa et al, 1997). In oesophageal SCC, we already reported that MT protein expression might be a significant determinant of prognosis, in particular, associated with cisplatin resistance (Hishikawa et al, 1997). Patients with MT protein-negative tumours survived longer when treated with cisplatin than those with MT protein-positive tumours. However, the exact biological significance of the expression of MT protein and mRNA is largely unknown in the clinical setting of oesophageal SCC.Therefore, in the present study, we have investigated the expressions of both MT mRNA and its protein in...

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Section: Immunohistochemistrymentioning

confidence: 99%

Metallothionein expression correlates with metastatic and proliferative potential in squamous cell carcinoma of the oesophagus

et al. 1999

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“…Counter staining for nuclei was done with hematoxylin. As a positive control normal human colonic mucosa, which was already reported to express MT [10], was used as a negative control nonimmune mouse serum was used instead of the primary antibody. …”

Section: Im M Unohistochem Ical Analysismentioning

confidence: 99%

Overexpression of Metallothionein Correlates with Chemoresistance to Cisplatin and Prognosis in Esophageal Cancer

et al. 1997

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The aim of this study was to determine the correlation of metallothionein (MT) expression with resistance to cisplatin and to identify prognostic factors in esophageal cancer. Immunostaining for MT was performed on the specimens of squamous cell carcinoma of the esophagus resected from 68 patients with curative intent. The expression of MT was evaluated in terms of clinicopathologic variables, effect of cisplatin, and the patients’ survival. Overexpression of MT in the tumor was found in 70.6% of the patients. Stage III and IV tumors were more common in MT-positive tumors (p = 0.0282) but there was no difference in other clinicopathologic variables between MT-positive and MT-negative groups. Stage, cisplatin therapy, and tumor length were the independent prognostic indicators by multivariate analysis. Among 43 patients treated with cisplatin, the 5-year survival rate was 56% for MT-negative and 26% for MT-positive patients (p = 0.0277). In the MT-negative patients, multivariate analysis revealed that curability, stage, cisplatin therapy, and tumor length were the independent prognostic factors. These findings suggest that MT expression in squamous cell carcinoma of the esophagus is a major determinant of the chemoresistance to cisplatin and may be a predictor of poor prognosis.

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“…The process of colonic tumor growth partly originates from complex interactions between growth factors, their inhibitors, and loss of tumor suppressor genes [13][14][15] . The epidermal growth factor (EGF) family of proteins includes a group of structurally related growth factors and receptors.…”

Section: Introductionmentioning

confidence: 99%

Does the EGFR and VEGF Expression Predict the Prognosis in Colon Cancer?

Döger¹,

Meteoğlu²,

Tuncyurek³

et al. 2006

Eur Surg Res

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Background/Aim: Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) are frequently encountered with aggressive tumor phenotype and poor prognosis, but the relationship between EGFR/VEGF expression and survival remains unclear. The aim of our study was to further investigate the prognostic value of EGFR and VEGF expression in colon cancer. Materials and Methods: The pathological specimens of 60 colon carcinoma patients were retrospectively evaluated and grouped according to EGFR and VEGF staining intensity and percentage of stained neoplastic cells. A final score was assigned to each case by multiplying percentage and staining score. The patients were stratified into the following categories: negative (score 0), low expression (score 1 or 2), and high expression (score 4). The remaining patient data were filtered out from the institutional cancer database. Results: The mean survival time was 28.93 ± 14.1 (range 2–52) months in the EGFR-negative group, 23.92 ± 14.0 (range 6–46) months in the group with a low EGFR expression, and 17.00 ± 12.8 (range 10–40) months in the group with a high EGFR expression. The median survival time was 27.50 ± 14.7 (range 4–52) months in the VEGF-negative group, 29.33 ± 12.8 (range 6–48) months in the group with a low VGEF expression, and 14.50 ± 14.2 (range 2–40) months in the group with a high VGEF expression. The expression of EGFR and VEGF was not an independent factor that affects survival. Conclusions: The EGFR and VEGF expression rates of colon tumors do not predict the survival. In addition, the EGFR expression in the primary tumor was not predictive of metastatic lymph nodes. The prognostic value of EGFR/VEGF staining may be further questioned.

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Alterations of Gene Expression in Human Colorectal Cancer

Cited by 10 publications

References 5 publications

Metallothionein expression correlates with metastatic and proliferative potential in squamous cell carcinoma of the oesophagus

Metallothionein expression correlates with metastatic and proliferative potential in squamous cell carcinoma of the oesophagus

Overexpression of Metallothionein Correlates with Chemoresistance to Cisplatin and Prognosis in Esophageal Cancer

Does the EGFR and VEGF Expression Predict the Prognosis in Colon Cancer?

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