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环氧化酶-2(COX-2)在非肿瘤性和肿瘤性外阴上皮病变中的表达。

Expression of cyclooxygenase-2 (COX-2) in non-neoplastic and neoplastic vulvar epithelial lesions.

作者信息

Ferrandina Gabriella, Ranelletti Franco Oreste, Salutari Vanda, Gessi Marco, Legge Francesco, Zannoni Gian Franco, Scambia Giovanni, Lauriola Libero

机构信息

Department of Obstetrics and Gynecology, Catholic University of the Sacred Heart, Rome, Italy.

出版信息

Gynecol Oncol. 2004 Feb;92(2):537-44. doi: 10.1016/j.ygyno.2003.10.054.

Abstract

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).

CONCLUSION

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.

摘要

目的

环氧化酶-2(COX-2)过表达与多种实体瘤的肿瘤侵袭性参数及不良临床结局相关。我们通过免疫组织化学方法研究了COX-2在正常外阴组织、非肿瘤性外阴上皮病变、外阴上皮内瘤变(VIN)和浸润性外阴癌(IVC)中的表达。

方法

研究了COX-2在正常外阴组织、6例硬化性苔藓(LS)、7例鳞状细胞增生(SCH)、20例VIN、2例佩吉特病及36例IVC中的表达模式。还探讨了IVC患者中COX-2表达与临床病理参数之间的关系。切片先与正常兔血清孵育15分钟,然后与抗人COX-2兔多克隆抗血清(美国密歇根州安阿伯市开曼公司)孵育。结果以COX-2积分密度值(IDV)的平均值±标准误(SE)表示。

结果

III-IV期(平均值±SE = 3.5±0.8)的肿瘤/基质COX-2 IDV比值高于I-II期疾病(平均值±SE = 1.4±0.3)(P值 = 0.04)。在I期病例亚组中,基质浸润>1 mm(T1b)的病例的肿瘤/基质COX-2 IDV值高于基质浸润≤1 mm(T1a)的病例(平均值±SE = 1.6±0.3对平均值±SE = 0.6±0.1)(P = 0.033)。此外,我们观察到有转移性淋巴结受累的病例的肿瘤/基质COX-2 IDV高于无淋巴结受累的病例(平均值±SE = 3.5±0.8对平均值±SE = 1.3±0.4)(P = 0.037)。

结论

本研究表明COX-2过表达可能有助于外阴肿瘤的发生和进展。此外,肿瘤/基质COX-2 IDV比值与肿瘤浸润范围和转移性淋巴结受累相关,而这两者是该肿瘤主要的预后参数,这意味着肿瘤/基质COX-2 IDV比值在外阴癌中可能具有预后作用。

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