title: Expression and clinical significance of Wee1 in colorectal cancer.
abstract: Wee1 is a nuclear kinase regulating cell cycle progression, and has emerged as a promising therapeutic target in cancer. Expression of Wee1 has been associated with poor outcome in certain tumor types, but the prognostic impact and clinical significance in colorectal cancer is unknown. The expression of Wee1 was examined by immunohistochemistry in primary colorectal carcinomas from a prospectively collected patient cohort, and associations with clinicopathological parameters and outcome were investigated. Cell culture experiments were performed using the cell lines RKO and SW620, and the relationship with the metastasis-promoting protein S100A4 was investigated. Nuclear expression was detected in 229 of the 258 tumors analyzed (89 %). Wee1 staining was associated with low pT stage, but no other significant associations with demographic or histopathological variables were found. Moderate Wee1 staining intensity was a predictor of favorable metastasis-free and overall survival compared to strong intensity and no or weak staining. The fraction of positive cells was not a prognostic factor in the present cohort. Inhibition of Wee1 expression using siRNA or treatment with the Wee1 inhibitor MK-1775 reduced expression of the metastasis-promoting protein S100A4, but no relationship between Wee1 and S100A4 was found in the patient samples. In conclusion, Wee1 is highly expressed in primary colorectal carcinomas, but few relevant associations with clinicopathological parameters or outcome were found. The lack of clinical significance of Wee1 expression could indicate that other tumor types might be better suited for further development of Wee1 inhibitors.
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, Nydalen, NO-0424, Oslo, Norway.
authors.forename: Eivind Valen
authors.initials: EV
authors.lastname: Egeland
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, Nydalen, NO-0424, Oslo, Norway.|Department of Gastroenterological Surgery, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.|Medical Faculty, University of Oslo, Oslo, Norway.
authors.forename: Kjersti
authors.initials: K
authors.lastname: Flatmark
authors.affiliation: Medical Faculty, University of Oslo, Oslo, Norway.|Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.affiliation: Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
authors.forename: Vivi Ann
authors.initials: VA
authors.lastname: Flørenes
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, Nydalen, NO-0424, Oslo, Norway.|Department of Pharmacy, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
authors.forename: Gunhild M
authors.initials: GM
authors.lastname: Mælandsmo
authors.affiliation: Department of Tumor Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, PO Box 4953, Nydalen, NO-0424, Oslo, Norway. kjetil.boye@rr-research.no.|Department of Oncology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. kjetil.boye@rr-research.no.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Boye
mesh_terms: D018797:Cell Cycle Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis* / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D011744:Pyrimidinones; D000071999:S100 Calcium-Binding Protein A4 / Q000032:analysis
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D011744:Pyrimidinones; D000071999:S100 Calcium-Binding Protein A4; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; C549567:adavosertib
keywords: Colorectal cancer; Prognostic marker; S100A4; Wee1