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p53 status: an indicator for 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, 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 Biomedicine and Surgery, Oncology. Linköping University, Faculty of Health Sciences.
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1999 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 51, no 2, 169-174 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Rectal carcinoma is a common malignancy, with a history of high local recurrence rates following surgery. In recent years. preoperative radiotherapy and refined surgical technique have improved local control rates.

AIM: To investigate the relationship between expression of nuclear p53 protein and the outcome in rectal carcinoma, with and without short-term preoperative radiotherapy.

MATERIAL: Specimens from 163 patients from the Southeast Swedish Health Care region included in the Swedish rectal cancer trial between 1987-1990.

METHOD: New sections from the paraffin blocks of the preoperative biopsy and the surgical specimen were examined immunohistochemically using a p53 antibody (PAb 1801).

RESULT: Expression of nuclear p53 protein was seen in 41% of the tumours. The p53 negative patients treated with preoperative radiotherapy had a significant reduction of local failure compared with the non-irradiated p53 negative patients (P = 0.0008). In contrast, p53 positive patients showed no benefit from preoperative radiotherapy. The interaction between p53 status and the benefit of radiotherapy was statistically significant (P = 0.018).

CONCLUSION: Expression of nuclear p53 protein in rectal carcinoma seems to be a significant predictive factor for local treatment failure after preoperative radiotherapy. Further investigations are necessary to select patients for preoperative treatment based on analysis of the preoperative biopsies.

Place, publisher, year, edition, pages
1999. Vol. 51, no 2, 169-174 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-24826DOI: 10.1016/S0167-8140(99)00041-9PubMedID: 10435809Local ID: 9223OAI: oai:DiVA.org:liu-24826DiVA: diva2:245148
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, GunnarSun, Xiao-FengStål, OlleKlintenberg, ClaesSjödahl, RuneNordenskjöld, Bo

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