Cyclooxygenase-2 expression in primary human colorectal cancers and bone marrow micrometastases.
BACKGROUND
Both the expressions of the inducible form of cyclooxygenase-2 and the presence of bone marrow micrometastases are poor prognostic markers in patients with colorectal carcinoma.


OBJECTIVE
As cyclooxygenase-2 expression in these tumours is associated with increased metastatic potential in vitro, our objectives were to determine the relationship between cyclooxygenase-2 and haematogenous spread to bone marrow.


METHODS
Thirty-two patients with resection of colorectal carcinoma were evaluated (median age: 69.5 years). Bone marrow was obtained from all patients from both iliac crests before manipulation of the primary tumour. The tumours were of varying stages at diagnosis (5 Dukes' A, 14 Dukes' B, 11 Dukes' C and 2 Dukes' D). Tumour sections were stained for cyclooxygenase-2 using the avidin-biotin immunohistochemical technique. Extent of staining was graded depending on the percentage of epithelial cells staining positive for cyclooxygenase-2. Micrometastases were detected by staining contaminant cytokeratin-18 positive cells in the bone marrow aspirates by either immunohistochemical (ARAAP) or immunological (flow cytometry) methods. Fisher's exact probability test was used to calculate statistical significance.


RESULTS
Cyclooxygenase-2 expression in the primary tumour was detected in 72% of the patients. Twelve (38%) patients had bone marrow micrometastases detected by either immunohistochemistry or flow cytometry. Of the 12 patients who had bone marrow micrometastases, 8 tumours demonstrated increased expression of cyclooxygenase-2 protein (66.6%). In contrast, 9 out of the 20 (45%) patients in whom micrometastases were not detected expressed increased levels of cyclooxygenase-2 (P = 0.29). When dividing the patients into subgroups of localised (Dukes' A and B) versus disseminated (Dukes' C and D) disease, there was no further association between cyclooxygenase-2 expression and bone marrow micrometastases (P = 0.179 and 1.0).


CONCLUSIONS
In this pilot study, there was no association between cyclooxygenase-2 expression and bone marrow micrometastases in patients with otherwise localised or disseminated disease.
Sheehan
K M
KM
Department of Pathology, Beaumont Hospital and Royal College of Surgeons, Beaumont Road, Dublin 9, Ireland. katherinesheehan@hotmail.com
Cahill
R A
RA
McGreal
G
G
Steele
C
C
Byrne
M F
MF
Kirwan
W O
WO
Kay
E W
EW
Fitzgerald
D J
DJ
Redmond
H P
HP
Murray
F E
FE
D000368:Aged; D000369:Aged, 80 and over; D019046:Bone Marrow Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000556:secondary*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010544:Peroxidases / Q000096:biosynthesis; D010865:Pilot Projects; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*
D007527:Isoenzymes; D008565:Membrane Proteins; D010544:Peroxidases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases