Expression of cyclooxygenase-2 (COX-2), receptors for estrogen (ER), and progesterone (PR), p53, ki67, and neu protein in endometrial cancer.
OBJECTIVE
We aimed at investigating by immunohistochemistry the relationship between cyclooxygenase-2 (COX-2) and estrogen (ER), and progesterone (PR) receptors in a single institution series of 90 primary untreated endometrial cancer patients. The simultaneous assessment of p53 protein, ki67, and neu protein has been carried out.


METHODS
Immunohistochemistry was performed on paraffin-embedded sections by using rabbit polyclonal antiserum against human COX-2, anti-ER (clone 1D5), and anti-PR (clone 1A6) monoclonal antibodies, anti ki67 (clone MIB-1) and p53 (clone DO-7), and polyclonal antibody anti human c-erbB2/neu.


RESULTS
There was no difference in the distribution of COX-2, p53, and neu positive cases according to ER or PR positivity, while the percentage of ki67 positive endometrial tumors was significantly higher in ER negative versus ER positive tumors (54.5% versus 31.6%, P value = 0.044). ER and PR positive tumors showed a statistically significant association with clinicopathological parameters of better clinical outcome. There was no clear association between COX-2 positivity and any of the clinicopathological features. The percentage of ki67, p53, and neu positive tumors was found to be strictly related to more aggressive features. Only advanced stage of disease was found to be a predictor of poor prognosis (P value = 0.034). None of the biological parameters examined was shown to be associated with patient outcome.


CONCLUSIONS
We showed that COX-2 expression is not correlated with ER, PR, p53, and neu, thus suggesting that COX-2-mediated activities may follow independent pathways. Our findings provide the rationale to design trials based on the combination of antihormones with inhibitors of COX-2 and neu in recurrent/metastatic endometrial cancer.
Gynecologic Oncology Unit, Catholic University of Rome, Catholic University of the Sacred Heart, Largo F. Vito 1, 00168 Rome, Italy. gabriella.ferrandina@libero.it
Gabriella
G
Ferrandina
Franco Oreste
FO
Ranelletti
Valerio
V
Gallotta
Enrica
E
Martinelli
Gian Franco
GF
Zannoni
Marco
M
Gessi
Giovanni
G
Scambia
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051546:Cyclooxygenase 2; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008565:Membrane Proteins; D008875:Middle Aged; D016612:Paraffin Embedding; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000096:biosynthesis*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D051546:Cyclooxygenase 2; D019394:Ki-67 Antigen; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C496540:PTGS2 protein, human