Tumour markers of prognosis in colorectal cancer

McLeod, Howard L.; Murray, Graeme I.

doi:10.1038/sj.bjc.6690033

Cited by 205 publications

(142 citation statements)

References 88 publications

(99 reference statements)

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“…Loss of heterozygosity (LOH) is one of the major types of genetic inactivation, and the long arm of chromosome 18 is the most frequently deleted region in colorectal cancers. To date, many reports suggest that this deletion is a molecular predictor that affects survival (Fearon et al, 1990;Jen et al, 1994;Chung, 1998;Lanza et al, 1998;Ogunbiyi et al, 1998;Jernvall et al, 1999;McLeod and Murray, 1999;Sarli et al, 2004). We too reported that the allelic deletion of chromosome 18q was associated with poorer prognosis in stage III colon cancer after adjuvant chemotherapy (Watanabe et al, 2001.…”

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confidence: 77%

Chromosome 18q deletion and Smad4 protein inactivation correlate with liver metastasis: a study matched for T- and N- classification

et al. 2006

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Smad4 protein, whose gene is coded at chromosome 18q21.1, is an important tumour suppressor that mediates transforming growth factor-beta. It has been reported that inactivation of the Smad4 gene and allelic loss of chromosome 18q correlate with liver metastasis and poorer prognosis in colorectal cancers. Utilising a recently developed method of immunohistochemical staining for Smad4 protein, we focused on the specific impact of Smad4 protein expression on liver metastasis in colorectal cancer. We also evaluated the association between chromosome18q deletion and liver metastasis. We selected 20 colorectal cancers with liver metastasis for the experimental group, and 20 cases without liver metastasis for the control. In order to exclude the influence of lymph node metastasis, all cases were lymph node negative. In addition, the two groups were matched for tumour depth, tumour differentiation and tumour location. We compared the expression level of Smad4 protein immunohistochemically in these 20 matched pairs. We also compared the loss of heterozygosity status at chromosome 18q in these 20 matched pairs. Immunohistochemical staining revealed a significant difference (P ¼ 0.024) in the level of Smad4 protein between the two groups. We also observed a significantly different (P ¼ 0.0054) ratio of allelic deletion at chromosome 18q21. Smad4 protein expression level and allelic loss at 18q21 are associated with the process of liver metastasis in colorectal cancers evaluated when excluding clinical and pathological features except for liver metastasis. (Vogelstein et al, 1988(Vogelstein et al, , 1989Benhattar et al, 1993;Kinzler and Vogelstein, 1996;Span et al, 1996;Kambara et al, 2004;Nassif et al, 2004). Loss of heterozygosity (LOH) is one of the major types of genetic inactivation, and the long arm of chromosome 18 is the most frequently deleted region in colorectal cancers. To date, many reports suggest that this deletion is a molecular predictor that affects survival (Fearon et al, 1990;Jen et al, 1994;Chung, 1998;Lanza et al, 1998;Ogunbiyi et al, 1998;Jernvall et al, 1999;McLeod and Murray, 1999;Sarli et al, 2004). We too reported that the allelic deletion of chromosome 18q was associated with poorer prognosis in stage III colon cancer after adjuvant chemotherapy (Watanabe et al, 2001. These reports suggest that there might be tumour suppressor genes located at chromosome 18q, which has a strong influence on survival. Smad4 gene, which mediates the intracellular signalling pathway of transforming growth factor (TGF)-beta receptor, has been detected as one of the target genes at 18q21 (Wang et al, 1995;Eppert et al, 1996;Hahn et al, 1996;Thiagalingam et al, 1996;Carethers et al, 1998;Markowitz, 2000;Fink et al, 2003;Alazzouzi et al, 2005;Li et al, 2005). Recently, an immunohistochemical method for evaluating Smad4 protein has been developed and several studies found higher frequency of Smad4 protein inactivation in the cases with liver metastasis and in the cases presenting unfavourable survival (Maitra et al, 20...

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confidence: 77%

Chromosome 18q deletion and Smad4 protein inactivation correlate with liver metastasis: a study matched for T- and N- classification

et al. 2006

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“…1,2 Approximately 40 -50% of all patients undergoing curative resection for colorectal carcinoma may die of recurrent disease and metastasis. [3][4][5] Reports suggest that half of the recurrent cancers may be detected within the first year after surgery, and 80 -90% of all recurrences may be detected within the first three years. 4 Therefore, new informative prognostic markers, which may identify high-risk patients after curative resection, are urgently needed for selection of patients for adjuvant treatment.…”

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confidence: 99%

“…4 Therefore, new informative prognostic markers, which may identify high-risk patients after curative resection, are urgently needed for selection of patients for adjuvant treatment. 3 In addition, postoperative surveillance after curative resection of colorectal carcinoma may be beneficial to give patients a second option for curative surgery. Serologic markers may be an option to perform such surveillance analyses, 6 and serum carcinoembryonic antigen (CEA) has been proposed as such a marker.…”

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confidence: 99%

High serum YKL‐40 level after surgery for colorectal carcinoma is related to short survival

Cintin

Johansen

Christensen

et al. 2002

Cancer

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“…Commercially available antibodies which have been widely used for prognostic investigations in colorectal cancer were chosen for the analysis (Baas et al, 1994;McLeod and Murray, 1999;Sturm et al, 1999).…”

Section: Bax and P53 Analysesmentioning

confidence: 99%

“…Recent investigations have focused on innovative molecular markers which may explain differences in the outcome of colorectal cancer patients belonging to a homogenous TNM stage group (McLeod and Murray, 1999).…”

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confidence: 99%

An analysis of p53, BAX and vascular endothelial growth factor expression in node-positive rectal cancer. Relationships with tumour recurrence and event-free survival of patients treated with adjuvant chemoradiation

Cascinu

Graziano

Catalano³

et al. 2002

Br J Cancer

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Tumours of patients with node-positive rectal cancer were studied by immunohistochemistry for p53, BAX and vascular endothelial growth factor expressions. Results were correlated to the relapse rate, the pattern of relapse and the event-free survival after radical surgery and adjuvant chemoradiation. After a median follow-up of 60 months, 39 patients remained disease-free and 40 patients relapsed (18 local relapses and 22 distant metastases). The majority of disease-free patients showed p53 negative and vascular endothelial growth factor negative tumours. Local relapses occurred more frequently in patients with p53 overexpressing tumours (P50.01), while distant metastases were in patients with vascular endothelial growth factor positive tumours (P50.003). Patients with p53 negative or vascular endothelial growth factor negative tumours showed better event-free survival than patients with p53 positive or vascular endothelial growth factor positive tumours. BAX analysis did not show any association with patients' outcome and it was unrelated to the p53 status. Adjuvant treatment strategies for node-positive rectal cancer may be improved by identifying categories of high-risk patients. In this study, vascular endothelial growth factor and p53 expressions correlated with recurrent disease, pattern of relapse and poor event-free survival.

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Tumour markers of prognosis in colorectal cancer

Cited by 205 publications

References 88 publications

Chromosome 18q deletion and Smad4 protein inactivation correlate with liver metastasis: a study matched for T- and N- classification

Chromosome 18q deletion and Smad4 protein inactivation correlate with liver metastasis: a study matched for T- and N- classification

High serum YKL‐40 level after surgery for colorectal carcinoma is related to short survival

An analysis of p53, BAX and vascular endothelial growth factor expression in node-positive rectal cancer. Relationships with tumour recurrence and event-free survival of patients treated with adjuvant chemoradiation

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