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Prognostic factors in colorectal cancer: aspects of tumour dissemination
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Immunology/Immunchemistry.
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Place, publisher, year, edition, pages
Umeå: Umeå Universitet , 2002. , 61 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 798
Keyword [en]
Colorectal neoplasms, prognosis, lymph node metastases, disseminated tumour cells, cytokeratins, micrometastases, metalloproteinases, immune cells, real-time quantitative RT-PCR, carsinoembryonic antigen
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-94103ISBN: 91-7305-264-7 (print)OAI: oai:DiVA.org:umu-94103DiVA: diva2:764204
Public defence
2002-09-20, Tandläkarhögskolan, Sal B, 9 tr., Umeå universitet, Umeå, 09:00
Opponent
Supervisors
Projects
digitalisering@umu
Note

Diss. (sammanfattning) Umeå : Umeå universitet, 2002

Available from: 2014-11-19 Created: 2014-10-03 Last updated: 2015-04-10Bibliographically approved
List of papers
1. Are lymph node micrometastases of any clinical significance in Dukes' stages A and B colorectal cancer?
Open this publication in new window or tab >>Are lymph node micrometastases of any clinical significance in Dukes' stages A and B colorectal cancer?
1998 (English)In: Diseases of the Colon & Rectum, ISSN 0012-3706, E-ISSN 1530-0358, Vol. 41, no 10, 1244-1249 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: The aim was to investigate the significance of lymph node micrometastases in Dukes Stages A and B colorectal cancer.

METHODS: Archival specimens were examined from 147 patients (96 colon, 51 rectum; 44 Stage A, 103 Stage B) who had surgery between 1987 and 1994. One lymph node section from each node (colon, 1-11; median, 4; rectum, 1-15; median, 3) was examined with use of an anticytokeratin antibody.

RESULTS: Forty-seven (32 percent) patients had micrometastases. At follow-up in June 1996, 23 patients had died of cancer or with known tumor relapse, after a median time of 28 (range, 5-67) months; 8 of 47 (17 percent) patients had micrometastases, 15 of 100 (15 percent) did not. No statistically significant differences were observed according to micrometastases when the results were analyzed with respect to Dukes stage or survival time. The median survival time of living patients with micrometastases was 48 (range, 18-97) months, and for patients without micrometastases, 48 (range, 19-111) months. Six of 96 living patients had a tumor relapse; three of these displayed micrometastases.

CONCLUSION: Lymph node micrometastases are not a useful prognostic marker in Dukes Stages A and B and do not imply different strategies for additional therapy or follow-up.

Place, publisher, year, edition, pages
Wolters Kluwer, 1998
Keyword
Colonic neoplasms, Cytokeratin, Immunohistochemistry, Lymph nodes, Micrometastases, Rectal neoplasms, Survival, Tumor stage
National Category
Gastroenterology and Hepatology Surgery
Identifiers
urn:nbn:se:umu:diva-68360 (URN)10.1007/BF02258221 (DOI)9788387 (PubMedID)
Projects
digitalisering@umu
Available from: 2013-04-17 Created: 2013-04-17 Last updated: 2017-12-06Bibliographically approved
2. Limited value of preoperative serum analyses of matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitors of matrix metalloproteinases (TIMP-1, TIMP-2) in colorectal cancer
Open this publication in new window or tab >>Limited value of preoperative serum analyses of matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitors of matrix metalloproteinases (TIMP-1, TIMP-2) in colorectal cancer
Show others...
2000 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 20, no 2B, 1085-1091 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: We studied whether preoperative serum levels of free MMP-2, the MMP-2/TIMP-2 complex, and total amounts of MMP-9, TIMP-1 and TIMP-2 correlated to the tumor stage and prognosis in colorectal cancer.

METHODS: Samples from 158 patients operated on for colorectal cancer (100 colon, 58 rectum) and samples from 80 healthy blood donors were analyzed using an ELISA technique. One hundred and thirty-three patients were resected for cure, (31, 61, and 41 in Dukes' stages A, B, and C, respectively). At follow-up in January 1998, 44 patients had died from their cancer after a median time 14 months (range 2-55). Fifteen patients died without tumor relapse. Ninety-nine patients were alive after, a median time of 46 months (range 17-68).

RESULTS: Wide, overlapping ranges were observed for all factors both in the patients and in the control group. The patients as compared to the control group had significantly higher levels of free MMP-2 and total amounts of MMP-9, TIMP-1 and TIMP-2, whereas the level of the MMP-2/TIMP-2 complex was significantly lower. TIMP-1 was significantly higher in Dukes' D compared to Dukes' A-C cases; the other factors did not correlate to tumor stage. Elevated TIMP-2 levels (median cut-off limit), only, correlated to worse prognosis when analysed in all patients (p < 0.05). None of the factors (median cut-off limit) correlated to survival in Dukes' A-C patients; analyses based on the upper quartile cut-off limit demonstrated that elevated MMP-2 levels correlated to shorter survival time (p < 0.05).

CONCLUSION: Serum analyses of free MMP-2 the MMP-2/TIMP-2 complex and total amounts of MMP-9, TIMP-1 and TIMP-2 are of limited value for tumor staging and prognosis in colorectal cancer.

National Category
Gastroenterology and Hepatology Surgery
Identifiers
urn:nbn:se:umu:diva-68361 (URN)10810401 (PubMedID)
Available from: 2013-04-17 Created: 2013-04-17 Last updated: 2017-12-06Bibliographically approved
3. Different occurrence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases from colorectal cancer as potential prognostic predictors
Open this publication in new window or tab >>Different occurrence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases from colorectal cancer as potential prognostic predictors
2002 (English)In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 17, no 1, 25-29 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: To study whether there are differences in the immunohistochemical staining of CD8, CD45R0, and CD68 of immune cells in regional lymph node metastases from colorectal cancer that are of potential interest in prognostic prediction.

MATERIALS AND METHODS: Analysis of archival specimens from 93 patients operated on for colorectal cancer (based on monoclonal antibodies, the ABC technique, and semiquantitative classification).

RESULTS: There was a significant difference in survival time between patients with respect to the number of positive immune cells. The cancer-specific 5-year survival rate was 77% for patients with high numbers of CD8+ cells, compared to 33% for those with lower numbers. The corresponding figures for patients with CD45R0+ cells were 66% vs. 33%, and for patients with CD68+ cells 60% vs. 38%. Significant differences remained among the 74 patients without adjuvant radio/chemotherapy regarding CD8 and CD45R0 but not CD68.

CONCLUSION: The presence of CD8+, CD45R0+, and CD68+ immune cells in regional lymph node metastases may serve as predictors of patients survival in colorectal cancer Dukes' stage C.

Place, publisher, year, edition, pages
Springer, 2002
National Category
Gastroenterology and Hepatology Surgery
Identifiers
urn:nbn:se:umu:diva-68362 (URN)10.1007/s003840100337 (DOI)12018450 (PubMedID)
Available from: 2013-04-17 Created: 2013-04-17 Last updated: 2017-12-06Bibliographically approved
4. Detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR for CEA and CK20 mRNAS
Open this publication in new window or tab >>Detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT-PCR for CEA and CK20 mRNAS
Show others...
2004 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 111, no 1, 101-110 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of our study was to develop specific, sensitive, objective assays for early detection of disseminated tumour cells in patients with colorectal cancer (CRC). Carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) were chosen as markers because they are selectively expressed in epithelial cells with maintained expression in CRC. Real-time quantitative RT-PCR assays with RNA copy standards were constructed. Regional lymph nodes were collected from patients with CRC (n = 51) and benign intestinal disease (n = 10). Results were compared to routine histopathology and anti-CEA immunohistochemistry. Lymph node levels of CEA and CK20 mRNA correlated strongly (p < 0.0001, r = 0.8). Lymph nodes from non-CRC patients had <0.01 CEA and <0.001 CK20 mRNA copies/18S rRNA unit. Lymph nodes from 3/6 Dukes' A, 17/26 Dukes' B, 10/10 Dukes' C and 7/9 Dukes' D patients had CEA mRNA levels above cut-off. Corresponding figures for CK20 mRNA were 3/6, 10/26, 9/10 and 5/9, respectively. CEA mRNA levels varied from 0.001 to 100 copies/18S rRNA unit in Dukes' A and B, and 50% of the Dukes' B patients had CEA mRNA levels within the range of Dukes' C patients. Three Dukes' B patients have died from CRC or developed distant metastases. All 3 had high CEA and CK20 mRNA levels. Determination of mRNA was superior to immunohistochemistry in showing CEA expression in lymph nodes. The present qRT-PCR assay for CEA mRNA seems to be a superior tool to identify individuals with disseminated tumour cells. Future extended studies will establish the clinically most relevant cut-off level.

Place, publisher, year, edition, pages
Geneve: International union against cancer, 2004
Keyword
colorectal neoplasm, carcinoembryonic antigen, cytokeratin 20, real-time quantitative RT-PCR, lymph node metastases, minimal residual cancer
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-21218 (URN)10.1002/ijc.20231 (DOI)15185350 (PubMedID)
Available from: 2009-04-07 Created: 2009-04-07 Last updated: 2017-12-13Bibliographically approved

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