Biochemical and clinical approaches in evaluating the prognosis of colon cancer.
BACKGROUND
Colorectal adenocarcinoma is a common malignant neoplasm in the Western world. To achieve optimal treatment results, the risk estimation of recurrence should be as accurate as possible.


METHODS
Tissue material from tumour and normal mucosa was taken from six patients and was analysed to screen aberrantly expressed genes using cDNA microarray. Selected up-regulated genes were chosen for further analysis by immunohistochemistry. For this purpose a tissue array material of 114 colorectal cancer patients was obtained. In addition to the routinely used proliferation marker Ki-67, the analysed proteins included securin and CDC25B.


RESULTS
Processes such as cellular defense, cell structure, motility and cell division were found to be notably represented among the most deregulated genes. A significant portion of the overexpressed genes included those functioning in the cell cycle. Immunohistochemical stainings of securin and CDC25B showed a consistent expression pattern with that of cDNA microarray analysis. There was no statistical association between the studied proliferation markers and survival. Instead, there was a significant association between the Dukes' class and the histological grade (p=0.04), but not between histological grade and survival. The survival of Dukes' B patients was significantly poorer if no regional lymph nodes were studied compared with the Dukes' B patients with even a single lymph node was studied (p=0.04, hazard ratio 2.7).


CONCLUSIONS
Tumour stage is superior in estimating the prognosis of patients with colonic cancer compared with the grading of cell cycle regulators or histological grade of the cancer. The study of regional lymph nodes is essential to identify the patients who would benefit from adjuvant chemotherapy.
Talvinen
Kati
K
Department of Pathology, University of Turku, 20520 Turku, Finland.
Tuikkala
Johannes
J
Grönroos
Juha
J
Huhtinen
Heikki
H
Kronqvist
Pauliina
P
Aittokallio
Tero
T
Nevalainen
Olli
O
Hiekkanen
Heikki
H
Nevalainen
Timo
T
Sundström
Jari
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D003110:Colonic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D064249:Securin; D015854:Up-Regulation; D020687:cdc25 Phosphatases / Q000096:biosynthesis / Q000235:genetics
D018797:Cell Cycle Proteins; D009363:Neoplasm Proteins; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases