Correlation of cyclooxygenase-2 (COX-2) and aromatase expression in human endometrial cancer: tissue microarray analysis.
OBJECTIVE
The objective of this study was to compare the prevalence of cyclooxygenase-2 (COX-2), aromatase, and hormone receptor immunohistochemical (IHC) expression to well defined clinical-pathologic prognostic factors in a large group of surgically staged endometrial cancer patients.


METHODS
A tissue microarray (TMA) was constructed from 336 separate specimens of endometrial cancer. IHC was performed for estrogen (ER) and progesterone (PR) receptor, COX-2, COX-1, and aromatase.


RESULTS
The majority of tumors expressed COX-2 (59%) and aromatase (65%). COX-2 staining significantly correlated with aromatase expression ( P < .014) but did not correlate with ER and PR. COX-2 expression was correlated with worsening histologic grade ( P < .026) and approached statistical significance for deep myometrial invasion ( P < .055). After applying multivariate analysis, no single IHC or combination of IHCs correlated with intrauterine poor prognostic factors or advanced stage. Only myometrial invasion >50% (OR 6.98, P < .001) and nonendometrioid histology (OR 4.933, P < .001) were predictive of advanced stage after multivariate analysis.


CONCLUSIONS
COX-2 and aromatase are expressed in the majority of endometrial cancer patients. COX-2 expression was not associated with the great majority of surgical-pathologic prognostic factors. COX-2 expression did significantly correlate with aromatase expression, suggesting that intratumoral production of estrogen in endometrial cancer may be an important mechanism in tumorigenesis.
Fowler
Jeffrey M
JM
Division of Gynecologic Oncology, The Ohio State University Medical School, Columbus, OH 43210, USA. Fowler-1@medctr.osu.edu
Ramirez
Nilsa
N
Cohn
David E
DE
Kelbick
Nicole
N
Pavelka
James
J
Ben-Shachar
Inbar
I
Morrison
Carl
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001141:Aromatase / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D051546:Cyclooxygenase 2; D016889:Endometrial Neoplasms / Q000201:enzymology* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008565:Membrane Proteins; D046228:Microarray Analysis; D008875:Middle Aged; D009367:Neoplasm Staging; D009924:Organ Culture Techniques; D011336:Probability; D011379:Prognosis; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D001141:Aromatase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases