DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study.
OBJECTIVE
The aim of this study was to determine TP53 and NM23-H1 immunoreactivity, DNA ploidy, and S-phase fraction (SPF) in a series of 160 patients undergoing resective surgery for primary operable colorectal cancer (CRC) and to establish whether these alterations have any clinical value in predicting CRC patients' prognosis.


METHODS
TP53 and NM23-H1 expressions were evaluated on paraffin-embedded tissue by immunohistochemistry and DNA-ploidy and SPF on frozen tissue by flow-cytometric analysis.


RESULTS
The median follow-up time in our study group was 71 months (range 34-115 months). P53 protein expression was associated with distal tumors (P<0.05) and DNA aneuploid tumors (P<0.05) tumors. DNA-aneuploidy was associated with distal tumors (P<0.01), histological grade (G3) (P<0.05), advanced Dukes' stage (C and D) (P<0.01), lymph node metastases (P<0.01) and high SPF (>18.3%) (P<0.01). The major significant predictors for both disease relapse and death were advanced Dukes' stage, DNA-aneuploidy, and high SPF, while lymphohematic invasion was the only independent factor for relapse and non-curative resection for death.


CONCLUSIONS
Our results indicate that DNA aneuploidy and high SPF are associated in CRC with a poor clinical 5-year outcome, while in contrast the prognostic role of TP53 and NM23-H1 expression is still to be clarified.
Bazan
V
V
School of Medicine, University of Palermo, Palermo, Italy.
Migliavacca
M
M
Zanna
I
I
Tubiolo
C
C
Corsale
S
S
Calò
V
V
Amato
A
A
Cammareri
P
P
Latteri
F
F
Grassi
N
N
Fulfaro
F
F
Porcasi
R
R
Morello
V
V
Nuara
R B
RB
Dardanoni
G
G
Salerno
S
S
Valerio
M R
MR
Dusonchet
L
L
Gerbino
A
A
Gebbia
N
N
Tomasino
R M
RM
Russo
A
A
D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002288:Adenocarcinoma, Mucinous / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis; D002455:Cell Division; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004273:DNA, Neoplasm / Q000235:genetics*; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D054778:NM23 Nucleoside Diphosphate Kinases; D009367:Neoplasm Staging; D009701:Nucleoside-Diphosphate Kinase; D011003:Ploidies; D011237:Predictive Value of Tests; D016196:S Phase; D016019:Survival Analysis; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins