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FXYD-3 expression in relation to local recurrence of rectal cancer
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Oncology.
Department of Surgery, Karolinska Institute, Stockholm, Sweden.
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2016 (English)In: Radiation Oncology Journal, ISSN 2234-1900 (print), 2234-3156 (online), Vol. 34, no 1, 52-58 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer.

Materials and Methods: FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81).

Results: Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without.

Conclusion: Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence.

Place, publisher, year, edition, pages
Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea , 2016. Vol. 34, no 1, 52-58 p.
Keyword [en]
Rectal cancer, Human FXYD3 protein, Local recurrence
National Category
Radiology, Nuclear Medicine and Medical Imaging Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-132758DOI: 10.3857/roj.2016.34.1.52PubMedID: 27104167OAI: oai:DiVA.org:liu-132758DiVA: diva2:1049023
Available from: 2016-11-23 Created: 2016-11-23 Last updated: 2016-12-07Bibliographically approved
In thesis
1. Response to neoadjuvant treatment in rectal cancer surgery
Open this publication in new window or tab >>Response to neoadjuvant treatment in rectal cancer surgery
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT.

Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer.

Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer.

Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour.

Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 66 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1553
National Category
Cancer and Oncology Surgery Clinical Laboratory Medicine Urology and Nephrology Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-132759 (URN)10.3384/diss.diva-132759 (DOI)9789176856383 (Print) (ISBN)
Public defence
2016-12-15, Hasselqvistsalen, Växthuset, Campus US, Linköping, 09:00 (Swedish)
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Available from: 2016-11-23 Created: 2016-11-23 Last updated: 2016-11-24Bibliographically approved

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Loftås, PerArbman, GunnarSun, Xiao-FengHallböök, Olof
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Division of Clinical SciencesFaculty of Medicine and Health SciencesDepartment of Surgery in NorrköpingDepartment of OncologyDepartment of Surgery in Linköping
Radiology, Nuclear Medicine and Medical ImagingCancer and Oncology

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