Department of Epidemiology, University of California, Irvine, School of Medicine, Irvine, CA, USA.
Br J Cancer. 2013 Feb 19;108(3):613-20. doi: 10.1038/bjc.2012.578. Epub 2013 Jan 8.
Lobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied.
In all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16(INK)4(a) (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology.
Out of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression.
Our study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection.
小叶宫颈腺上皮增生（LEGH）是宫颈的一种罕见病变。有人提出，LEGH 可能代表一组与高危型人乳头瘤病毒（H-HPV）感染无关的具有胃型表型的黏液性腺癌（GA）的癌前病变。碳酸酐酶-IX（CA-IX）在常规腺性病变（CGLs）中高度表达。然而，CA-IX 在 LEGH 或 GA 中的表达尚未研究。
总共从细胞学诊断为意义不明的非典型腺细胞的日本女性中确定了 12 例 CGLs、7 例 LEGHs、6 例共存原位腺癌（AIS，3 例）和 GA（3 例）。使用免疫组化检测组织中的 CA-IX 和 p16(INK)4(a)（以下简称 p16）蛋白表达以及巴氏涂片（PSs）中的 CA-IX 蛋白表达。聚合酶链反应用于检测液基细胞学中的 H-HPV DNA。
在 12 例（83%）CGLs 中，有 10 例 H-HPV 阳性，所有病例（100%）均显示高水平的 CA-IX 表达。在 12 例中有 11 例（92%）观察到 p16 蛋白表达。无 LEGH、LEGHs 伴 AIS 或 GA 对 H-HPV 阳性，仅有 8 例（62%）显示局灶性弱（1+）p16 表达。相比之下，所有病例（100%）均显示出强烈的 CA-IX 蛋白表达。
我们的研究表明，CGLs 与 LEGHs 伴 AIS 或 GA 的致癌发生机制不同。LEGHs 与 GAs 之间也可能存在关联。此外，CA-IX 表达可能作为在缺乏 H-HPV 感染的情况下检测 GAs 的有用生物标志物。
