Expression of cyclooxygenase-2 (COX-2) in non-neoplastic and neoplastic vulvar epithelial lesions.
OBJECTIVE
Cyclooxygenase-2 (COX-2) overexpression has been associated with parameters of tumor aggressiveness and unfavourable clinical outcome in several solid tumors. We investigated by immunohistochemistry the expression of COX-2 in normal vulvar tissue, non-neoplastic vulvar epithelial lesions, vulvar intraepithelial neoplasia (VIN) and invasive vulvar cancer (IVC).


METHODS
The expression pattern of COX-2 was studied in normal vulvar tissue, in six cases of lichen sclerosus (LS), seven cases of squamous cell hyperplasia (SCH), 20 VIN, 2 Paget's disease and 36 IVC. The relationship between COX-2 expression and clinicopathologic parameters in IVC patients has been also addressed. Sections were incubated with normal rabbit serum for 15 min, then with rabbit polyclonal antiserum against human COX-2 (Cayman, Ann Arbor, MI, USA). The results were reported as mean +/- standard error (SE) of COX-2 integrated density values (IDV).


RESULTS
Higher levels of tumor/stroma COX-2 IDV ratio were found in stages III-IV (mean +/- SE = 3.5 +/- 0.8) than stages I-II disease (mean +/- SE = 1.4 +/- 0.3) (P value = 0.04). In the subgroup of stage I cases, tumor/stroma COX-2 IDV values were higher in cases with > 1 mm stromal invasion (T1b) than cases with <== 1 mm stromal invasion (T1a) (mean +/- SE = 1.6 +/- 0.3 vs. mean +/- SE = 0.6 +/- 0.1) (P = 0.033). Moreover, we observed higher tumor/stroma COX-2 IDV in cases with metastatic lymph node involvement than cases without lymph node involvement (mean +/- SE = 3.5 +/- 0.8 vs. mean +/- SE = 1.3+/-0.4) (P = 0.037).


CONCLUSIONS
This study suggests that COX-2 overexpression may contribute to vulvar tumorigenesis and progression. Moreover, the correlation of tumor/stroma COX-2 IDV ratio with tumor extension and metastatic lymph node involvement, which represent the major prognostic parameters in this neoplasia, implies that tumor/stroma COX-2 IDV ratio could have a prognostic role in vulvar cancer.
Ferrandina
Gabriella
G
Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.
Ranelletti
Franco Oreste
FO
Salutari
Vanda
V
Gessi
Marco
M
Legge
Francesco
F
Zannoni
Gian Franco
GF
Scambia
Giovanni
G
Lauriola
Libero
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D051546:Cyclooxygenase 2; D004848:Epithelium / Q000201:enzymology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D008875:Middle Aged; D009367:Neoplasm Staging; D010145:Paget Disease, Extramammary / Q000201:enzymology / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D014844:Vulva / Q000201:enzymology*; D014845:Vulvar Diseases / Q000201:enzymology / Q000473:pathology; D014846:Vulvar Neoplasms / Q000201:enzymology* / Q000473:pathology
D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases