Cohn David E, Frankel Wendy L, Resnick Kimberly E, Zanagnolo Vanna L, Copeland Larry J, Hampel Heather, Kelbick Nicole, Morrison Carl D, Fowler Jeffrey M
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, the Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, Ohio 43210, USA.
Obstet Gynecol. 2006 Nov;108(5):1208-15. doi: 10.1097/01.AOG.0000239097.42987.0c.
To correlate survival and surgical-pathologic factors with DNA mismatch repair status in patients with endometrial cancer.
Specimens from 336 patients with endometrial cancer were used to create a tissue microarray. Immunohistochemistry with antibodies against the mismatch repair genes MLH1, MSH2, MSH6, and PMS2 were used to stain the tissue microarray. Clinical, pathologic, and survival data were collected and correlated with the immunohistochemistry results.
Mismatch repair deficiency was seen in 29% (84 of 294) of cases. Correlation was noted between lack of expression of MLH1 and an increased risk for lymphvascular space involvement (32% versus 21%, P=.05) and cervical involvement (26% versus 14%, P=.02). Lack of expression of either MLH1 or MSH2 was associated with thinner patients (85% had a body mass index less than 40 versus 73% of patients with normal expression, P=.02), as well as with the absence of a history of previous primary malignancy (0 verus 13 cases [4%], P=.023). The estimated disease-free survival is 88%; despite a small number of recurrences, there was a nonsignificant improvement in disease-free survival in tumors with an intact mismatch repair system (P=.1). Significantly improved disease-free survival was seen in patients with normal MLH1 and MSH2 expression compared with those with abnormal expression (92% versus 81%, P=.035).
Defects in DNA mismatch repair in endometrial cancer is correlated with negative prognostic factors and worse progression-free survival (without a difference in overall survival) compared with tumors with an intact mismatch repair system.
II-3.
探讨子宫内膜癌患者的生存及手术病理因素与DNA错配修复状态之间的相关性。
采用336例子宫内膜癌患者的标本制作组织芯片。使用针对错配修复基因MLH1、MSH2、MSH6和PMS2的抗体进行免疫组织化学染色，对组织芯片进行染色。收集临床、病理和生存数据，并与免疫组织化学结果进行相关性分析。
294例病例中有29%（84例）存在错配修复缺陷。MLH1表达缺失与淋巴血管间隙浸润风险增加（32%对21%，P = 0.05）和宫颈浸润风险增加（26%对14%，P = 0.02）相关。MLH1或MSH2表达缺失与体型较瘦的患者相关（85%的体重指数小于40，而正常表达患者为73%，P = 0.02），也与既往无原发性恶性肿瘤病史相关（0例对13例[4%]，P = 0.023）。估计无病生存率为88%；尽管复发例数较少，但错配修复系统完整的肿瘤在无病生存率方面有非显著性改善（P = 0.1）。与表达异常的患者相比，MLH1和MSH2表达正常的患者无病生存率显著提高（92%对81%，P = 0.035）。
与错配修复系统完整的肿瘤相比，子宫内膜癌中DNA错配修复缺陷与不良预后因素及较差的无进展生存期相关（总生存期无差异）。
II - 3。
