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Survivin expression is an independent prognostic factor in rectal cancer patients with and without preoperative radiotherapy
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
2004 (Engelska)Ingår i: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 60, nr 1, s. 149-155Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Purpose: Survivin, as an inhibitor of apoptosis, is undetectable in normal tissues but expressed in tumors. Survivin expression in rectal cancer patients who have undergone preoperative radiotherapy (RT) alone has not been studied. We analyzed the relationships of survivin expression to RT, clinicopathologic variables, apoptosis, and p53 expression in rectal cancer patients who participated in a trial of preoperative RT. Methods and Materials: Survivin was immunohistochemically examined in 98 rectal tumors (74 had adjacent normal mucosa). Of 98 patients, 57 underwent surgery alone and 41 underwent RT before surgery. Results: Survivin positivity was related to worse survival, independent of Dukes' stage, local and distant recurrence, differentiation, gender, age, apoptosis, and p53 expression (p = 0.02). Survivin was not associated with survival in the patients without (p = 0.08) or with (p = 0.19) RT. After RT, survivin tended to be increased in adjacent normal mucosa (p = 0.057) but not in tumors (p = 0.71). Conclusion: Survivin was independently related to survival in rectal cancer patients who participated in a trial of preoperative RT, but not in either treatment group (surgery alone or surgery plus RT). Whether the effect of survivin on tumors is associated with RT and further related to patient survival needs to be investigated in a larger number of patients. (C) 2004 Elsevier Inc.

Ort, förlag, år, upplaga, sidor
2004. Vol. 60, nr 1, s. 149-155
Nyckelord [en]
radiotherapy, prognosis, rectal cancer, immunohistochemistry
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-46183DOI: 10.1016/j.ijorbp.2004.02.007OAI: oai:DiVA.org:liu-46183DiVA, id: diva2:267079
Tillgänglig från: 2009-10-11 Skapad: 2009-10-11 Senast uppdaterad: 2018-02-27
Ingår i avhandling
1. Biological and histological factors as predictors in rectal cancer patients: A study in a clinical trial of preoperative radiotherapy
Öppna denna publikation i ny flik eller fönster >>Biological and histological factors as predictors in rectal cancer patients: A study in a clinical trial of preoperative radiotherapy
2011 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

With improved surgical techniques and preoperative radiotherapy (RT) the local recurrence rate in rectal cancer patients has been reduced, however the mortality rate is still high and there is a huge variation in the response to preoperative RT in patients with the same tumour stage. To improve patient’s survival, it is of great importance to identify good prognostic and predictive factors that help us to select the best suited patients for preoperative RT in the future.

For many years, studies of neoplastic transformation have mainly focused on tumour cells. In recent years, researchers have realised that the stroma around tumour cells and their extracellular matrix components also play an important role in tumour carcinogensesis.

The aim of this thesis was to investigate the biological factors, survivin and particularly interesting new cysteine-histidine rich protein (PINCH), histological factors, inflammatory infiltration, fibrosis, necrosis, mucinous content, angiogenesis and lymphangiogenesis as well as their relationships to preoperative RT and to clinical variables in rectal cancer patients who participated in a Swedish rectal cancer trial of preoperative RT.

In paper I, the expression of survivin and its relationship to preoperative RT and clinical factors were investigated in 98 primary rectal tumours and adjacent normal mucosa. In all patients, positive survivin expression was independently related to worse survival compared to negative survivin expression in a multivariate analysis.

In paper II, PINCH expression and its relationship to RT, clinical, histological and biological factors were investigated at the invasive margin and inner tumour area in 137 primary rectal tumours and in cell line of fibroblasts. In patients without RT, strong PINCH expression was independently related to worse survival in a multivariate analysis. No survival relationship was found in the patients with RT, and there was no difference in PINCH expression between the subgroups of non-RT and RT at the invasive margin/inner tumour area. In patients with RT, strong PINCH expression at the inner tumour area was related to a high level of lymphatic vessel density (LVD).

In paper III, the frequency of LVD/blood vessel density (BVD) was analysed at the periphery, the inner tumour area and the invasive margin of 138/140 primary rectal tumours and correlated to RT, clinical, histological and biological factors. In all patients, LVD at the periphery of the tumour was independently related to better survival compared to LVD at the inner tumour area/invasive margin. In all patients, a higher LVD at the periphery was related to negative (wild type) p53 expression.

In paper IV, the inflammatory infiltration, fibrosis, necrosis and mucinous content were studied in relation to RT, clinical and biological parameters in preoperative biopsies (n = 153) and in primary tumours (n = 148). In all patients and in the subgroups of non-RT and RT a higher grade of inflammatory infiltration was independently related to improved survival compared to weak inflammatory infiltration in a multivariate analysis.

In this thesis, survivin, PINCH, LVD and inflammatory infiltration are independent prognostic factors in rectal cancer patients who participated in a clinical trial of preoperative RT. This information may help us to improve patient’s survival by selecting the best suited patients for preoperative RT in the future.

Ort, förlag, år, upplaga, sidor
Linköping: Linköping University Electronic Press, 2011. s. 71
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1226
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
urn:nbn:se:liu:diva-66207 (URN)978-91-7393-234-9 (ISBN)
Disputation
2011-03-25, Linden, Hälsouniversitetet, Ingång 65, Campus US, Linköpings univeristet, Linköping, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2011-07-05 Skapad: 2011-03-08 Senast uppdaterad: 2020-02-03Bibliografiskt granskad

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