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Decreased tumor cell proliferation as an indicator of the effect of preoperative radiotherapy of rectal cancer
Linköping University, Department of Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Biomedicine and Surgery, Cell biology. Linköping University, Faculty of Health Sciences.
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.
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2001 (English)In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 50, no 3, 659-663 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Rectal cancer is a common malignancy, with significant local recurrence and death rates. Preoperative radiotherapy and refined surgical technique can improve local control rates and disease-free survival.

PURPOSE: To investigate the relationship between the tumor growth fraction in rectal cancer measured with Ki-67 and the outcome, with and without short-term preoperative radiotherapy.Method: Ki-67 (MIB-1) immunohistochemistry was used to measure tumor cell proliferation in the preoperative biopsy and the surgical specimen.

MATERIALS: Specimens from 152 patients from the Southeast Swedish Health Care region were included in the Swedish rectal cancer trial 1987-1990.

RESULTS: Tumors with low proliferation treated with preoperative radiotherapy had a significantly reduced recurrence rate. The influence on death from rectal cancer was shown only in the univariate analysis. Preoperative radiotherapy of tumors with high proliferation did not significantly improve local control and disease-free survival. The interaction between Ki-67 status and the benefit of radiotherapy was significant for the reduced recurrence rate (p = 0.03), with a trend toward improved disease-free survival (p = 0.08). In the surgery-alone group, Ki-67 staining did not significantly correlate with local recurrence or survival rates.

CONCLUSION: Many Ki-67 stained tumor cells in the preoperative biopsy predicts an increased treatment failure rate after preoperative radiotherapy of rectal cancer.

Place, publisher, year, edition, pages
2001. Vol. 50, no 3, 659-663 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-24827DOI: 10.1016/S0360-3016(01)01515-2PubMedID: 11395233Local ID: 9224OAI: oai:DiVA.org:liu-24827DiVA: diva2:245149
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically 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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Adell, GunnarZhang, HongJansson, AgnetaSun, Xiao-FengStål, OlleNordenskjöld, Bo

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