Department of Pathology, Johns Hopkins Hospital Medical Institutions, Baltimore, MD 21287, USA.
Hum Pathol. 2011 Nov;42(11):1613-9. doi: 10.1016/j.humpath.2011.01.007. Epub 2011 Apr 14.
The histogenesis of clear cell adenocarcinoma of the bladder/urethra is uncertain. Hepatocyte nuclear factor-1β is a homeodomain protein that has been reported to be frequently overexpressed in ovarian clear cell adenocarcinoma in comparison with rare or no expression in other types of epithelial ovarian tumors. We assessed the expression of hepatocyte nuclear factor-1β in a series of 18 clear cell adenocarcinomas of the bladder and urethra and compared it with that of invasive high-grade transitional/urothelial carcinoma (n = 35); adenocarcinomas of the bladder, urethra, and paraurethral glands (n = 21); as well as nephrogenic adenomas of the bladder (n = 8). Staining intensity and extent were evaluated using a 4-tiered grading system (0-3). A case was considered positive for hepatocyte nuclear factor-1β if 10% or more of tumor cells showed at least weak nuclear staining or if any moderate or strong nuclear staining was observed. All 18 clear cell adenocarcinomas exhibited nuclear staining in at least 50% of tumor cells (16 strong, 1 moderate, and 1 weak with focal strong nuclear staining) in comparison with positive nuclear staining (moderate) in 1 of 21 bladder adenocarcinoma, 1 of 35 invasive high-grade transitional/urothelial carcinoma (weak to moderate staining), and 2 of 8 nephrogenic adenomas (1 weak and 1 moderate to strong staining). We concluded that hepatocyte nuclear factor-1β is a useful marker in differentiating clear cell adenocarcinomas of the bladder/urethra from invasive high-grade transitional/urothelial carcinoma and other types of bladder adenocarcinomas and to a lesser extent from nephrogenic adenomas. Hepatocyte nuclear factor-1β is of no diagnostic utility in discriminating primary bladder/urethral clear cell adenocarcinomas from metastatic clear cell adenocarcinomas of the female genital tract to the bladder/urethra. From a histogenesis standpoint, although the expression of hepatocyte nuclear factor-1β in both gynecologic and urologic tract clear cell adenocarcinomas may point to a Müllerian derivation/differentiation, this immunohistochemical evidence is insufficient to completely exclude an urothelial association.
膀胱/尿道透明细胞腺癌的组织发生尚不确定。肝细胞核因子-1β 是一种同源域蛋白，据报道在卵巢透明细胞腺癌中频繁过度表达，而在其他类型的卵巢上皮性肿瘤中则很少或没有表达。我们评估了一系列 18 例膀胱和尿道透明细胞腺癌中肝细胞核因子-1β的表达，并将其与浸润性高级别移行/尿路上皮癌（n = 35）；膀胱、尿道和尿道旁腺腺癌（n = 21）；以及膀胱肾源性腺瘤（n = 8）进行比较。使用 4 级分级系统（0-3）评估染色强度和范围。如果 10%或更多的肿瘤细胞显示至少弱核染色，或者观察到任何中度或强核染色，则认为病例为肝细胞核因子-1β阳性。与 21 例膀胱腺癌中 1 例（中度）、35 例浸润性高级别移行/尿路上皮癌中 1 例（弱至中度染色）和 8 例肾源性腺瘤中 2 例（1 例弱、1 例中度至强染色）相比，所有 18 例透明细胞腺癌的肿瘤细胞至少有 50%显示核染色（16 例强、1 例中度、1 例弱且有局灶性强核染色）。我们的结论是，肝细胞核因子-1β是一种有用的标志物，可将膀胱/尿道透明细胞腺癌与浸润性高级别移行/尿路上皮癌和其他类型的膀胱腺癌区分开来，与肾源性腺瘤的区分程度较小。肝细胞核因子-1β在鉴别原发性膀胱/尿道透明细胞腺癌与女性生殖道转移至膀胱/尿道的透明细胞腺癌方面无诊断价值。从组织发生学的角度来看，尽管妇科和泌尿系统透明细胞腺癌中肝细胞核因子-1β的表达可能指向 Müllerian 来源/分化，但这种免疫组织化学证据不足以完全排除尿路上皮的关联。
