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Infiltration of mononuclear inflammatory cells into primary colorectal carcinomas: an immunohistological analysis
Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Neuroscience and Locomotion, Pathology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
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1997 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 75, no 3, 374-380 p.Article in journal (Refereed) Published
Abstract [en]

Local immunoregulation mediated by mononuclear tumour-infiltrating cells is considered of importance for tumour progression of colorectal cancer, although the balance between immunosuppressor and cytotoxic activities is unclear. Colorectal cancers from 26 patients were investigated using a panel of monoclonal antibodies in order to identify subsets of mononuclear inflammatory cells and to study their pattern of distribution in relation to tumour stage and cytotoxic immune reactivity against the tumour. In all but five tumours, mononuclear cells, lymphocytes or monocytes were present in fairly large numbers, particularly in the stroma. The infiltration of CD4+ mononuclear cells predominated over the CD8+ subset. Infiltration near the tumour cells was found in four cancers only. Stromal infiltration of CD11c+ macrophages was found in all but eight tumours. Small regressive areas, in which the histological architecture of the tumours was broken down, were found in 17 tumours with intense or moderate infiltration by CD4+ lymphocytes or CD11c+ macrophages. Probably this destruction of tumour tissue was caused by cytotoxic activity of the tumour-infiltrating mononuclear cells. In Dukes' class A and B tumours, CD4+ lymphocytes predominated over CD4+ cells with macrophage morphology, but the latter were increasingly found in Dukes' class C and D disease. The occurrence of MHC II-positive macrophages and lymphocytes in different Dukes' classes was similar to that of CD4+ cells. In contrast to this, CD11c+ and CD11a+ cells were more frequent in Dukes' A and B class tumours compared with Dukes' C and D. Four out of nine tumours of the latter stages showed a poor inflammatory reaction. The interpretation of our results is that the subsets of tumour-infiltrating mononuclear cells change with advancing Dukes' class and that the local immune control is gradually broken down in progressive tumour growth, even if some cytotoxic activity is still present.

Place, publisher, year, edition, pages
1997. Vol. 75, no 3, 374-380 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-79592PubMedID: 9020482OAI: oai:DiVA.org:liu-79592DiVA: diva2:543876
Available from: 2012-08-10 Created: 2012-08-10 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Indicators of colorectal cancer prognosis and response to preoperative radiotherapy
Open this publication in new window or tab >>Indicators of colorectal cancer prognosis and response to preoperative radiotherapy
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Colorectal cancer is one of the three most common malignant diseases in Sweden, with about 5,000 new cases each year. Thirty-five percent of these are rectal cancer, for which local recurrence after surgery has been a serious problem. The five-year survival rate in colorectal cancer has improved from about 40% in 1960 to 55% in 1995. Adjuvant chemotherapy of colon cancer, preoperative radiotherapy and improved surgical techniques in rectal cancer have contributed to the improved  results. To select patients best suited for pre- or postoperative therapy, we need indicators of both prognosis and response to therapy.

Using antibodies against cytokeratin, we found that 39% of patients with colorectal carcinoma that had penetrated the muscularis propria but without lymph-node metastases by routine light microscopy, had got micrometastases. Survival among patients with micrometastases was not significantly different from that among patients without such metastases.

We also identified subsets of tumour-infiltrating mononuclear cells and studied their pattern of distribution in relation to regressive tumour areas and Dukes class. Our interpretation is that the subsets of tumourinfiltrating mononuclear cells change with advancing Dukes class, indicating gradual deterioration of the local immune control.

We also investigated the interaction between p53, Ki-67, apoptosis and the outcome in rectal cancer with and without short-term preoperative radiotherapy. The expression of nuclear p53 protein seemed to be a significant predictive factor for local treatment failure after preoperative radiotherapy. Low tumour cell proliferation measured with Ki-67 in the preoperative biopsy correlated with improved local control and disease-free survival after preoperative radiotherapy.

High apoptotic index was associated with improved local control of rectal cancer even without pre-operative radiotherapy, whereas local control of tumours with low and intermediate apoptotic index was significantly improved by preoperative radiotherapy.

In conclusion, micrometastases in regional lymph nodes are an interesting phenomenon but with limited prognostic value. The subsets of tumour-infiltrating mononuclear cells change with advancing Dukes class, and its seems that the local immune control is gradually broken down. In rectal cancer, p53 expression, tumour proliferation measured with Ki-67 and apoptotic index seem to be interesting indicators of rectal cancer prognosis and response to preoperative radiotherapy.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2000. 53 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 626
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25542 (URN)9989 (Local ID)91-7219-583-5 (ISBN)9989 (Archive number)9989 (OAI)
Public defence
2000-05-12, Onkologens föreläsningssal, Hälsouniversitetet, Campus US, Linköpings Universitet, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-08-10Bibliographically approved

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