Farley John, Uyehara Catherine, Hashiro Glenn, Belnap Christina, Birrer Michael, Salminen Eric
Department of Obstetrics and Gynecology, Tripler Army Medical Center, TAMC, HI 96859-5000, USA.
Gynecol Oncol. 2004 Feb;92(2):596-602. doi: 10.1016/j.ygyno.2003.10.052.
To evaluate the expression of Cox-2 protein by immunohistochemistry in cervical dysplasias, and to determine any relationship to clinical factors such as degree or recurrence of dysplasia.
Immunohistochemical expression of p27 and Cox-2 was initially examined in 62 cervical LEEP specimens, which spanned the histologic spectrum from benign to severe dysplasia. Histology and cytology from colposcopic follow-up exams were reviewed for 1 year after LEEP procedure. Primary outcome variable was recurrent dysplasia, either cytologic or histologic. Statistical analysis utilizing chi-square test for trend and Fisher's Exact tests were performed to determine relative risk of recurrent dysplasia.
A total of 62 LEEP specimens were examined by immunohistochemistry (IHC). This included 18 mild, 19 moderate, and 25 severely dysplastic LEEP specimens. The percentage of tumor cells in each specimen that stained for p27 protein or Cox-2 enzyme was documented. A specimen was considered positive for p27 or Cox-2 if 50% or more of the cells in a specimen were stained: 94% of mild, 89% of moderate, and 44% of severe dysplasias stained positive for p27; 50% of mild, 42% of moderate, and 68% of severe dysplasia specimens stained positive for Cox-2. The average intensity of Cox-2 staining increased with severity of dysplasia-1.6 for mild, 1.8 for moderate, and 2.1 for severe dysplasia. There was a significant increase in both Cox-2 and p27 staining when severely dysplastic specimens were compared to mild and moderate dysplasia (P < 0.001). Of the 35 specimens that stained positive for Cox-2 protein, 59% of these specimens had positive Cox-2 staining that extended to the margins of the LEEP resection specimen. The average length of Cox-2 protein staining beyond the histologic dysplasia was 1.64 mm. Positive margin status for Cox-2 was a significant independent risk factor for persistent and recurrent dysplasia, RR 1.68 95% CI (1.07 < RR < 2.65), P < 0.027.
Cox-2 and p27 protein expression could be involved in squamous cervical cancer carcinogenesis. Cox-2 staining is often found outside the dysplastic lesion and this factor is associated with an increased risk of persistent and recurrent dysplasia following LEEP procedure. Should the histologic margin of LEEP resection approach 2.0 mm, follow-up algorithms for these patients should include intensive surveillance to ensure adequate treatment of disease.
通过免疫组织化学评估Cox-2蛋白在宫颈发育异常中的表达，并确定其与发育异常程度或复发等临床因素之间的关系。
最初在62例宫颈环形电切术（LEEP）标本中检测p27和Cox-2的免疫组织化学表达，这些标本涵盖了从良性到重度发育异常的组织学范围。在LEEP手术后1年，对阴道镜随访检查的组织学和细胞学结果进行回顾。主要结局变量是细胞学或组织学上的复发性发育异常。利用趋势卡方检验和Fisher精确检验进行统计分析，以确定复发性发育异常的相对风险。
共对62例LEEP标本进行了免疫组织化学（IHC）检查。其中包括18例轻度、19例中度和25例重度发育异常的LEEP标本。记录每个标本中p27蛋白或Cox-2酶染色的肿瘤细胞百分比。如果标本中50%或更多的细胞被染色，则该标本被认为p27或Cox-2呈阳性：94%的轻度、89%的中度和44%的重度发育异常标本p27染色呈阳性；50%的轻度、42%的中度和68%的重度发育异常标本Cox-2染色呈阳性。Cox-2染色的平均强度随着发育异常程度的加重而增加——轻度为1.6，中度为1.8，重度发育异常为2.1。与轻度和中度发育异常相比，重度发育异常标本中的Cox-2和p27染色均显著增加（P < 0.001）。在35例Cox-2蛋白染色呈阳性的标本中，59%的标本Cox-2阳性染色延伸至LEEP切除标本的边缘。Cox-2蛋白染色超出组织学发育异常的平均长度为1.64 mm。Cox-2切缘阳性状态是持续性和复发性发育异常的显著独立危险因素，相对风险1.68，95%可信区间（1.07 < 相对风险 < 2.65），P < 0.027。
Cox-2和p27蛋白表达可能参与宫颈鳞状细胞癌的致癌过程。Cox-2染色常出现在发育异常病变之外，且该因素与LEEP术后持续性和复发性发育异常风险增加相关。如果LEEP切除的组织学切缘接近2.0 mm，这些患者的随访方案应包括强化监测，以确保疾病得到充分治疗。
