Loss of p27 expression and microsatellite instability in sporadic colorectal cancer

The role of the loss of p27 protein expression in the oncogenesis of colorectal cancer is still in debate. In this study, we prospectively examined the immunohistochemical expression of p27 in 108 consecutive colorectal cancers, and we analysed the relationship with the results, the clinicopathologi...

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Published in:	Surgical oncology Vol. 15; no. 2; pp. 97 - 106
Main Authors:	Sarli, Leopoldo, Bottarelli, Lorena, Azzoni, Cinzia, Campanini, Nicoletta, Di Cola, Gabriella, Barilli, Angela Luciana, Marchesi, Federico, Mazzeo, Antonio, Salvemini, Carlo, Morari, Silvia, Di Mauro, Davide, Donadei, Enrico, Necchi, Fransesca, Roncoroni, Luigi, Bordi, Cesare
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ltd 01-08-2006 Elsevier Limited
Subjects:	Adenocarcinoma - genetics Adenocarcinoma - metabolism Adult Aged Aged, 80 and over Colorectal cancer Colorectal Neoplasms - genetics Colorectal Neoplasms - metabolism Deoxyribonucleic acid DNA Female Fhit Gene Expression Regulation, Neoplastic hMlh1 hMsh2 Humans Immunohistochemistry Kinases Loss of Heterozygosity Male Microsatellite Instability Microsatellite Repeats Middle Aged MSI p27 Polymerase Chain Reaction Proliferating Cell Nuclear Antigen - biosynthesis Proteins Studies Surgery Treatment Outcome MSI p27 Fhit hMsh2 hMlh1 Colorectal cancer
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Summary:	The role of the loss of p27 protein expression in the oncogenesis of colorectal cancer is still in debate. In this study, we prospectively examined the immunohistochemical expression of p27 in 108 consecutive colorectal cancers, and we analysed the relationship with the results, the clinicopathological data, microsatellite instability (MSI) and other genetic alterations of tumours. Unselected patients (108) who underwent curative colorectal resection for sporadic colorectal cancer in a three-year period were evaluated for MSI using 6 microsatellite markers, and for the presence of p27, p53, Fhit, Mlh1 and Msh2 proteins by means of immunostaining. The relationships between these markers were analysed. p27 protein expression was examined for association with disease recurrences and survival. Lack of p27 expression was noted in 33 out of 108 (30.5%) colorectal cancer cases ( P<0.05). This altered expression was significantly higher in proximal cancers ( P<0.05), mucinous tumours ( P<0.001), poorly differentiated histology ( P<0.01), cancers with MSI ( P<0.05), tumours with altered expression of Mlh1 ( P<0.01), of Msh2 ( P<0.05), and of Fhit ( P<0.01). Overall survival was better in the patient group with altered level of phenotypic p27 expression, although the difference does not reach statistical significance ( P=0.069). The analysis performed only for patients with tumour at stage II showed significantly better survival when the tumour exhibited altered p27 expression ( P<0.02). The results of the present study support the hypothesis that altered expression of p27 may be part of the genetic pathway involving MSI, which is responsible for the development of some colorectal cancers.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-7404 1879-3320
DOI:	10.1016/j.suronc.2006.09.002