Intestinal Low-grade Tubuloglandular Adenocarcinoma in Inflammatory Bowel Disease
Intestinal Low-grade Tubuloglandular Adenocarcinoma in Inflammatory Bowel Disease
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炎症性肠病中的肠道低度管状腺癌
DOI：
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发表时间：
2006
影响因子：
5.6
通讯作者：
N. Harpaz
中科院分区：
文献类型：
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作者：
Gabriel S Levi;N. Harpaz
慢性特发性炎症性肠病（IBD）与广泛的结肠累及容易发展成结肠腺癌。在这种情况下发生的癌症类型中，有一种异常分化良好的低级别管腺腺癌（LGTGA），迄今尚未进行系统研究。在我们机构进行的149例ibd相关肿瘤切除术的回顾中，根据以下组织学特征，17例（11%）患者的21例肿瘤被分类为LGTGA：分化非常良好的小到中等直径腺体，呈圆形或管状，低级别细胞学特征，缺乏或缺乏促结缔组织增生反应。溃疡性结肠炎12例，克罗恩病4例，不确定性结肠炎1例。他们的中位年龄为41.5岁（28 - 58岁）。5名患者分别患有常规类型的同步癌症。LGTGAs的大小从0.4到10厘米不等，大体外观各不相同。其中包括5例扁平性病变，肉眼无法识别，但通过触诊未固定的手术标本（1例）或组织学随机切片（4例）检测到。浸润性腺体通常与上覆的低级别或不确定的发育不良隐窝具有密切的组织学相似性。12例（57%）LGTGA浅表区明确的癌在组织学上进展为深部常规腺癌。这些肿瘤明显比整个过程中维持低级别组织学的9个癌更晚期。13例患者（76%）平均随访4.0年（范围0.75 - 9.0年），10例（77%）预后良好，3例（23%）预后不良。2个不良结局可归因于同步晚期常规癌症，3个不良结局可归因于从LGTGA进展为低分化腺癌。LGTGA上覆及周围粘膜表现为低级别发育不良（LGD） 18例（86%），不明确发育不良伴局灶性LGD 1例（5%），LGD伴局灶性高度发育不良（HGD） 2例（10%）。免疫组织化学研究显示MUC2的表达率为72%，MUC6的表达率为0%，CK7的表达率为69%，CK20的表达率为100%。CK7和CK20的共表达在LGTGA衍生的常规腺癌区域中是保守的。11个肿瘤中有6个（55%）发生了hMLH1免疫组织化学表达沉默，暗示其发病机制中存在DNA复制错误修复缺陷。我们得出结论，LGTGA是一种独特的临床病理实体，其特征是直接衍生于IBD的LGD粘膜，形态分化非常好，CK7和CK20频繁共表达，hMLH1频繁沉默。从LGTGA到常规类型腺癌的组织学进展与临床进展相似。LGD可能直接导致LGTGA，并通过LGTGA导致更具侵袭性的癌症，这加强了对诊断为LGD的IBD患者进行积极治疗的建议。
Chronic idiopathic inflammatory bowel disease (IBD) with extensive colonic involvement predisposes to the development of colorectal adenocarcinoma. Among the types of cancer occurring in this setting is an unusually well-differentiated low-grade tubuloglandular adenocarcinoma (LGTGA) that has not been studied systematically thus far. A review of 149 IBD-associated cancer resections performed at our institution yielded 17 patients (11%) with 21 tumors classified as LGTGA based on the following histologic characteristics: very well-differentiated small to medium diameter glands with round or tubular profiles, low-grade cytologic characteristics and absence or paucity of desmoplastic reaction. Twelve patients had ulcerative colitis, 4 Crohn disease, and 1 indeterminate colitis. Their median age was 41.5 years (range, 28 to 58 y). Five patients had separate synchronous cancers of conventional types. LGTGAs ranged from 0.4 to 10 cm in size and varied in gross appearance. They included 5 flat lesions that were not identified visually but were detected either by palpation of the unfixed surgical specimen (1 case) or histologically in random sections (4 cases). The invasive glands usually bore a close histologic resemblance to overlying low-grade or indefinite dysplastic crypts. Twelve carcinomas (57%) with well-defined superficial regions of LGTGA progressed histologically to conventional adenocarcinoma in deeper regions. These tumors were significantly more advanced than 9 carcinomas that maintained low-grade histology throughout. Follow-up of 13 patients (76%) for a mean 4.0 years (range, 0.75 to 9.0 y) disclosed 10 (77%) with favorable outcomes and 3 (23%) with adverse outcomes. Two adverse outcomes were attributable to synchronous advanced-stage conventional cancers and the third to progression from LGTGA to poorly differentiated adenocarcinoma. The mucosa overlying and surrounding LGTGA showed low-grade dysplasia (LGD) in 18 cases (86%), indefinite dysplasia with focal LGD in 1 case (5%), and LGD with focal high-grade dysplasia (HGD) in 2 cases (10%). Immunohistochemical studies disclosed expression of MUC2 in 72%, MUC6 in 0%, CK7 in 69%, and CK20 in 100%. Coexpression of CK7 and CK20 was conserved in regions of conventional adenocarcinoma derived from LGTGA. Silencing of immunohistochemical expression of hMLH1 occurred in 6 of 11 tumors tested (55%), implicating defective DNA replication error repair in their pathogenesis. We conclude that LGTGA is a distinct clinicopathologic entity characterized by direct derivation from LGD mucosa of IBD, very well-differentiated morphology, frequent coexpression of CK7 and CK20, and frequent silencing of hMLH1. Histologic progression from LGTGA to conventional types of adenocarcinoma parallels clinical progression to more aggressive neoplasia. The potential of LGD to give rise directly to LGTGA, and by way of LGTGA to more aggressive cancers, reinforces recommendations in favor of aggressive management of IBD patients diagnosed with LGD.
影响因子：
3.2
作者：
Weiss, AA;Babyatsky, MW;Itzkowitz, SH
通讯作者：
Itzkowitz, SH
影响因子：
11.2
作者：
A. Fleisher;M. Esteller;N. Harpaz;A. Leytin;A. Rashid;Yan Xu;Jingliang Liang;O. Stine;Jing Yin-Jing
通讯作者：
A. Fleisher;M. Esteller;N. Harpaz;A. Leytin;A. Rashid;Yan Xu;Jingliang Liang;O. Stine;Jing Yin-Jing
影响因子：
29.4
作者：
CHANG, SK;DOHRMAN, AF;KIM, YS
通讯作者：
KIM, YS