| 1. |
- Emterling, A, et al.
(författare)
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Clinicopathological significance of microsatellite instability and mutated RIZ in colorectal cancer
- 2004
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 15:2, s. 242-246
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have shown that microsatellite instability (MSI) is related to favourable survival in colorectal cancer patients but there are controversial results. Tumour suppressor gene RIZ is a susceptible mutational target of MSI. However, its clinicopathological significance has not been investigated. We investigated the prognostic significance of MSI in Swedish colorectal cancer patients and the clinicopathological significance of RIZ mutations. Patients and methods: We analysed 438 colorectal adenocarcinomas for MSI by microsatellite analysis. Among them, 29 MSI and 28 microsatellite stable (MSS) tumours were examined for RIZ mutations by DNA sequencing. Results: MSI (13% of 438 cases) was not associated with survival (rate ratio=0.97, 95% confidence interval =0.57-1.64, P=0.90), although it was related to proximal tumour (P <0.001), poor differentiation and mucinous carcinomas (P <0.001), multiple tumours (P=0.01) and negative/weak expression of hMLH1 (P=0.03). RIZ mutations were detected in 31% of 29 MSI tumours but in none of the 28 MSS tumours. The mutations were related to female (P=0.01), proximal tumour (P=0.01), stage B (P=0.01) and poor differentiation (P=0.047). Conclusions: MSI was not a prognostic factor in the Swedish patients included in this study. Clinicopathological variables associated with RIZ mutations might be a consequence of the MSI characteristics.
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| 2. |
- Emterling, Anna, et al.
(författare)
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Clinicopathological significance of Nup88 expression in patients with colorectal cancer
- 2003
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Ingår i: Oncology. - : S. Karger AG. - 0890-9091 .- 0030-2414 .- 1423-0232. ; 64:4, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The nucleoporin Nup88 is overexpressed in a series of human malignancies, however, its clinicopathological significance has not been studied. Our aims were to analyze Nup88 expression in normal mucosa, primary tumors and metastases from colorectal cancer patients and further to identify relationships of Nup88 expression with clinicopathological and other factors.Materials and Methods: Using immunohistochemistry, we investigated Nup88 expression in 198 primary colorectal tumors, 96 normal mucosa samples and 35 lymph node metastases.Results: The results showed that the intensity of Nup88 expression increased from the normal mucosa to the primary tumors (p < 0.0001) and tended to increase from the primary tumors to the metastases (p = 0.15). Both primary tumors and metastases presented stronger expression in the invasive margin and vascular-invaded areas. Nup88 expression was positively related to distal tumor location (p = 0.01), infiltrative growth pattern (p = 0.04) and higher proliferative activity (p = 0.04) and reversely to the grade of differentiation (p = 0.02) and apoptosis (p = 0.049). Strong expression of Nup88 predicted a worse outcome in the patients with distal tumors during the follow-up period of up to 3 years (p = 0.02).Conclusions: It seems that overexpression of Nup88 was involved in the tumorigenesis and aggressiveness of colorectal cancers, and Nup88 may be used as a prognostic factor in patients with distal tumors.
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| 3. |
- Evertsson, Sofia, 1972-, et al.
(författare)
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Microsatellite instability and MBD4 mutation in unselected colorectal cancer
- 2003
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 23:4, s. 3569-3574
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We investigated the prognostic significance of microsatellite instability (MSI) and the association with clinicopathological factors in colorectal cancer, and further identified MBD4 mutations and their clinicopathological significance.PATIENTS AND METHODS: MSI was analyzed in 201 colorectal cancers. Sequencing analysis of MBD4 was performed in 26 MSI and 28 microsatellite stable (MSS) tumors.RESULTS: Twenty-seven tumors (13.4%) were MSI but did not correlate with improved survival. MSI was significantly correlated with proximal colon tumors (p < 0.001), poor differentiation or mucinous type (p = 0.005) and multiple tumors (p = 0.04). MBD4 mutations were found in 15% MSI but not in MSS tumors. The mutated cases showed female overrepresentation, proximal site and poorly-differentiated/mucinous type.CONCLUSION: MSI was not correlated with survival, but shared other features associated with MSI in colorectal cancer as demonstrated by others. The clinicopathological variables associated with the MBD4 mutations were probably the reflection of MSI features.
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| 4. |
- Gao, Jingfang, et al.
(författare)
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Stromal staining for PINCH is an independent prognostic indicator in colorectal cancer
- 2004
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Ingår i: Neoplasia. - : Elsevier BV. - 1522-8002 .- 1476-5586. ; 6:6, s. 796-801
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Tidskriftsartikel (refereegranskat)abstract
- Particularly interesting new cysteine-histidine-rich protein (PINCH), a LIM domain adapter protein that functions in the integrin and growth factor signal transduction pathway, is upregulated in stroma associated with many common cancers. The finding suggested that PINCH may be involved in promoting tumor-stromal interactions that support tumor progression, and, if so, tumors with abundant PINCH stromal staining may have a worse prognosis. To test this hypothesis, 174 primary colorectal adenocarcinomas with 39 distant normal mucosa samples and 26 metastases in the lymph nodes were studied by immunohistochemistry, and 7 additional colon tumors were studied by Western blot analysis and immunofluorescence. The abundance of PINCH protein in stroma increased from normal mucosa to primary tumor to metastasis (P < .05), and was more intense at the invasive margin than it was in the intratumoral stroma. Strong stromal immunostaining for PINCH was shown to predict a worse outcome (rate ratio 2.1, 95% CI 1.16-3.37, P = .01), independent of Dukes stage, growth pattern, and tumor differentiation. PINCH was detected in fibroblasts, myofibroblasts, and a proportion of endothelial cells of the tumor vasculature, supporting the involvement of PINCH in promoting tumor-stromal interactions that support tumor progression. Interestingly, stromal staining for PINCH was an independent prognostic indicator in colorectal cancer.
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| 5. |
- Jansson, Agneta, 1973-, et al.
(författare)
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Combined deficiency of hMLH1, hMSH2, hMSH3 and hMSH6 is an independent prognostic factor in colorectal cancer
- 2003
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Ingår i: International Journal of Oncology. - 1019-6439 .- 1791-2423. ; 22:1, s. 41-49
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Tidskriftsartikel (refereegranskat)abstract
- We examined biological and clinicopathological significance of individual and combined hMLH1, hMSH2, hMSH3 and hMSH6 expression with immunohistochemistry in 301 unselected colorectal cancers. Weak hMLH1 expression was correlated to microsatellite instability (P=0.04), negative p53 expression (P=0.005) and mucinous carcinomas (P=0.02). Weak hMSH2 expression was related to negative ras (P<0.001) and p53 expression (P=0.005), and better survival (P=0.03). hMSH2, hMSH3 and hMSH6, as well as hMLH1, hMSH2, hMSH3 and hMSH6, were combined into a 'functional' and a 'less-functional' group, respectively. Both 'less-functional' groups were/tended to be associated with microsatellite instability, negative ras and p53 expression, and better survival. In summary, hMLH1 and hMSH2 were more important when investigated individually, and the combined groups were more related to the mutator pathway, suggesting that combined deficiencies of the proteins are more efficiently involved in the mutator pathway. Our result from weak versus strong staining may suggest that the intensity of staining should be considered in future studies on mismatch repair proteins.
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| 6. |
- Jansson, Agneta, 1973-, et al.
(författare)
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mRNA and protein expression of PUMA in sporadic colorectal cancer.
- 2004
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Ingår i: Oncology Reports. - 1021-335X .- 1791-2431. ; 12:6, s. 1245-1249
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Tidskriftsartikel (refereegranskat)abstract
- PUMA is a BH3-only member of the Bcl-2 family, up-regulated by p53 as a response to DNA damage. We have investigated the mRNA expression of PUMA with real-time PCR in 94 colorectal adenocarcinomas and the corresponding normal mucosa. Among them PUMA protein expression was investigated with immunohistochemistry in 23 tumours and 17 corresponding normal mucosa samples. The mRNA expression of PUMA decreased in 4% and increased in 4% of the tumours compared with the normal mucosa. The protein expression of PUMA decreased in 6% and increased in 29% of the tumours compared with the normal mucosa. Decreased PUMA expression in the tumour compared with the corresponding mucosa was correlated with the distal colon and rectum (P=0.02). We did not find any other relationship to clinical or pathological features. We suggest that the changes in PUMA expression may be of minor importance in the development of colorectal cancer.
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| 7. |
- Jansson, Agneta, 1973-, et al.
(författare)
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Noxa in colorectal cancer : A study on DNA, mRNA and protein expression
- 2003
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 22:30, s. 4675-4678
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Tidskriftsartikel (refereegranskat)abstract
- Noxa is a BH3-only member of the Bcl-2 family, upregulated by p53 as a response to DNA damage. Mutations in the BH3-only region of other BH3-only members lead to an inactive protein. We have investigated the mRNA expression of Noxa with real-time PCR in 94 unselected colorectal adenocarcinomas and the corresponding normal mucosa. Among them, Noxa protein expression was investigated with immunohistochemistry in 16 tumors and six corresponding normal mucosa samples. Further, we searched for Noxa mutations in all the cases using single-stranded conformation polymorphism and DNA sequencing. The mRNA expression of Noxa was weak in 9% and strong in 2% of the tumors, and decreased in 9% and increased in 16% of the tumors compared with the normal mucosa, however, these changes did not have any clinical or pathological significance. The protein level in most of the cases investigated was correlated with the mRNA level. We did not find any mutations in the Noxa gene. Thus, we suggest that Noxa may not be of importance in the development of colorectal cancer.
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| 8. |
- Skoglund, Johanna, et al.
(författare)
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Clinicopathological significance of stromelysin-3 expression in colorectal cancer
- 2004
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Ingår i: Oncology. - : S. Karger AG. - 0890-9091 .- 0030-2414 .- 1423-0232. ; 67:1, s. 67-72
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Stromelysin-3 (ST3) is a member of the matrix metalloproteinases and suggested to play a role in tissue remodeling observed in growth and metastasis of tumors. ST3 overexpression in breast cancer is associated with a worse outcome. Our aims were to analyze ST3 expression in primary colorectal tumors and metastases, and further to identify relationships of the expression to clinicopathological factors. Materials and Methods: ST3 expression was immunohistochemically analyzed in 200 primary colorectal adenocarcinomas and 36 corresponding lymph node metastases. Results: Scoring was performed by counting the percentages of positive cells and the percentages of positive areas. One hundred and one (51%) cases showed ≤5% positive cells and 99 (49%) >5% positive cells. One hundred and two (51%) cases showed ≤30% positive area and 98 (49%) >30% positive area. ST3 expression determined by both scoring methods was individually related to females, distally located tumors, infiltrative growth pattern and microsatellite stability. No relationship was found with age, Dukes' stage, differentiation and survival. Conclusions: These results suggest that ST3 protein was more involved in the pathway of colorectal cancer development in females, distal locations, infiltrative growth patterns and microsatellite stability. Copyright © 2004 S. Karger AG, Basel.
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| 9. |
- Zhang, Hong, 1957-, et al.
(författare)
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Codon 201 polymorphism of DCC gene is a prognostic factor in patients with colorectal cancer
- 2003
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Ingår i: Cancer Detection and Prevention. - 0361-090X .- 1873-443X. ; 27:3, s. 216-221
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Tidskriftsartikel (refereegranskat)abstract
- The polymorphism at codon 201 of the "deleted in colorectal carcinoma" (DCC) gene has been liked to susceptibility to colorectal cancer. However, its clinicopathological significance has not been reported. We examined the codon 201 polymorphism and loss of heterozygosity (LOH) by PCR-restriction fragment length polymorphism (PCR-RFLP) in 59 colorectal cancers, 48 samples from transitional mucosa and 67 samples from normal mucosa. The frequencies of the polymorphism did not significantly differ from normal to transitional mucosa and to tumor, but LOH was increased from transitional mucosa to tumor. Almost all of the LOH cases showed the polymorphism. The polymorphism was increased from well/moderately to poorly differentiated and to mucinous carcinoma (P = 0.03). The polymorphism was more frequently seen in advanced stages than in earlier stages (P = 0.02), and further predicted worse survival (P = 0.04). The data suggest that the codon 201 polymorphism of the DCC gene was a target of LOH, and predicted prognosis in colorectal cancer patients. ⌐ 2003 International Society for Preventive Oncology. Published by Elsevier Science Ltd. All rights reserved.
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