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- Holmqvist, Annica, 1974-
(författare)
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Biological and histological factors as predictors in rectal cancer patients : A study in a clinical trial of preoperative radiotherapy
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 2. |
- Holmqvist Knutsen, Annica, 1974-, et al.
(författare)
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PINCH is an independent prognostic factor in rectal cancer patients without preoperative radiotherapy : A study in a Swedish rectal cancer trial of preoperative radiotherapy
- 2012
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407 .- 1471-2407. ; 12:65
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients. Material and Methods: PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by Western blot. Results: In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (p = 0.03). No survival relationship in patients with RT was observed (p = 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (p = 0.68)/inner tumour area (p = 0.49). Conclusions: PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.
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