Loss of p27 expression and microsatellite instability in sporadic colorectal cancer.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Sarli
Leopoldo
L
Department of Surgical Sciences, Section of General Surgical Clinics and Surgical Therapy, Parma University, Medical School, Via Gramsci 14, 43100 Parma, Italy. leosarli@unipr.it
Bottarelli
Lorena
L
Azzoni
Cinzia
C
Campanini
Nicoletta
N
Di Cola
Gabriella
G
Barilli
Angela Luciana
AL
Marchesi
Federico
F
Mazzeo
Antonio
A
Salvemini
Carlo
C
Morari
Silvia
S
Di Mauro
Davide
D
Donadei
Enrico
E
Necchi
Fransesca
F
Roncoroni
Luigi
L
Bordi
Cesare
C
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D018895:Microsatellite Repeats; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis*; D016896:Treatment Outcome
D018809:Proliferating Cell Nuclear Antigen; C413374:p27 antigen