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The location of lymphangiogenesis is an independent prognostic factor in rectal cancers with or without preoperative radiotherapy
Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Oncology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
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2010 (English)In: ANNALS OF ONCOLOGY, ISSN 0923-7534, Vol. 21, no 3, 512-517 p.Article in journal (Refereed) Published
Abstract [en]

Background: Lymphangiogenesis and angiogenesis are essential for tumour development and progression. The lymphatic vessel density (LVD) and blood vessel density (BVD) and their relationship to outcome have been studied extensively, however the clinical significance of the location of LVD/BVD in tumour is not known. In the present study, the location and degree of LVD/BVD and their relationship to preoperative radiotherapy (RT), clinicopathological, histopathological and biological factors were studied in rectal cancer patients participating in a Swedish clinical trial of preoperative RT. Patients and methods: The location and degree of LVD/BVD were analysed in primary tumours (n = 138/140) and in their subgroups of non-RT (n = 74) and RT (n = 64/66). Further, the degree of LVD/BVD was examined in the corresponding distant normal mucosa (n = 35/31) and adjacent normal mucosa (n = 72/91). All sections were immunohistochemically examined by using D2-40 and CD34 antibodies. Results: In the whole series of the patients, a higher LVD at the periphery was related to negative p53 expression (P = 0.03) and favourable survival independent of tumour-node-metastasis stage, differentiation and p53 expression (P = 0.03). LVD was increased in p53-negative tumours after RT (P = 0.01). Conclusion: LVD at the periphery of the tumour was an independent prognostic factor in rectal cancer patients.

Place, publisher, year, edition, pages
2010. Vol. 21, no 3, 512-517 p.
Keyword [en]
angiogenesis, lymphangiogenesis, prognosis, radiotherapy, rectal cancer
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-54786DOI: 10.1093/annonc/mdp486ISI: 000276045300012OAI: oai:DiVA.org:liu-54786DiVA: diva2:309831
Note
This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Annals of Oncology following peer review. The definitive publisher-authenticated version: A Holmqvist, Jingfang Gao, Gunnar Adell, John Carstensen and Xiao-Feng Sun, The location of lymphangiogenesis is an independent prognostic factor in rectal cancers with or without preoperative radiotherapy, 2010, ANNALS OF ONCOLOGY, (21), 3, 512-517. is available at: http://dx.doi.org/10.1093/annonc/mdp486 Copyright: Oxford University Press http://www.oxfordjournals.org/ Available from: 2010-04-09 Created: 2010-04-09 Last updated: 2011-09-21
In thesis
1. Biological and histological factors as predictors in rectal cancer patients: A study in a clinical trial of preoperative radiotherapy
Open this publication in new window or tab >>Biological and histological factors as predictors in rectal cancer patients: A study in a clinical trial of preoperative radiotherapy
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
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.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 71 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1226
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-66207 (URN)978-91-7393-234-9 (ISBN)
Public defence
2011-03-25, Linden, Hälsouniversitetet, Ingång 65, Campus US, Linköpings univeristet, Linköping, 09:00 (Swedish)
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Supervisors
Available from: 2011-07-05 Created: 2011-03-08 Last updated: 2011-12-05Bibliographically approved

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Gao, JingfangAdell, GunnarCarstensen, JohnSun, Xiao-Feng

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