“Filiform” Serrated Adenomas: A Clinicopathologic and Immunophenotypic Study of 18 Cases
“Filiform” Serrated Adenomas: A Clinicopathologic and Immunophenotypic Study of 18 Cases
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“丝状”锯齿状腺瘤：18例临床病理及免疫表型研究
DOI：
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发表时间：
2007
影响因子：
5.6
通讯作者：
R. Odze
中科院分区：
文献类型：
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作者：
R. Yantiss;Kirstine Oh;Yao;M. Redston;R. Odze
在这项研究中，我们描述了一个以前没有特点的类型腺瘤性息肉的结直肠，显示突出，薄，细长的突起的肿瘤上皮与锯齿状轮廓，我们称之为“丝状锯齿状腺瘤”（SA）。对18例丝状SA患者和23例传统（非丝状）SA患者的经内镜处理的息肉切除标本进行临床和病理学特征评价，并对各种标记物（O 6-甲基鸟嘌呤甲基转移酶、MLH 1、MSH 2、CDX 2、核β-连环蛋白、p53和Ki-67）进行化学染色，以评价其分子和增殖特征。从石蜡包埋的材料中提取DNA，通过聚合酶链反应扩增，并分析微卫星不稳定性、BRAF、K-ras和p53突变状态。5例病例含有足够的非肿瘤组织进行解剖和DNA提取，允许分析杂合性缺失。研究组包括7名男性和11名女性，平均年龄64岁（范围：42 - 89岁）。所有18例丝状SA均位于左结肠，其中15例（83%）发生在直肠，对照组为43%（P=0.03）。丝状SA（1.6 cm）也大于SA（平均值：1.2 cm，P=0.02），但未观察到其他临床差异。大多数（56%）丝状SA含有显着的基质水肿和高的非粘液细胞丰富的嗜酸性细胞质（61%）。4/18例（22%）病例存在高度异型增生。4例（22%）丝状SA还含有非锯齿状腺瘤成分，具有绒毛状（3例）或管状（1例）生长模式。2例（11%）包含无蒂SA的相邻区域，4例（22%）有增生区域。对照组中没有息肉显示间质水肿、高度异型增生或混合成分。两组息肉的O 6-甲基鸟嘌呤甲基转移酶、MLH-1、MSH-2、CDX 2、β-连环蛋白和Ki-67染色模式相似，均未显示核p53表达增加。5/12（42%）丝状SA存在低频微卫星不稳定，7/12（58%）微卫星稳定。71%的病例中存在丝裂原活化蛋白激酶途径异常[7/14例（50%）BRAF和3/14例（21%）K-ras突变]。4例经直接测序显示p53基因沉默突变，4例在所评估的位点显示杂合性缺失，包括1例D5 S346 [腺瘤性结肠息肉病（APC）基因]，1例D17 S250（p53基因）和2例MYCL（染色体1 p34）。我们的结论是丝状SA可能代表了SA的一个不寻常的变种，好发于左结肠，特别是直肠。
In this study, we describe a previously uncharacterized type of adenomatous polyp of the colorectum that shows prominent, thin, elongated projections of neoplastic epithelium with a serrated contour, which we have termed “filiform serrated adenoma” (SA). Routinely processed polypectomy specimens from 18 patients with filiform SA and 23 controls with traditional (nonfiliform) SA were evaluated for their clinical and pathologic features, and immunohistochemically stained for a variety of markers (O6-methylguanine methyltransferase, MLH1, MSH2, CDX2, nuclear β-catenin, p53, and Ki-67) designed to evaluate their molecular and proliferative characteristics. DNA was extracted from the paraffin-embedded materials, amplified by polymerase chain reaction, and analyzed for microsatellite instability, BRAF, K-ras, and p53 mutational status. Five cases contained sufficient non-neoplastic tissue for dissection and DNA extraction, allowing analysis of loss of heterozygosity. The study group consisted of 7 males and 11 females of mean age 64 years (range: 42 to 89 y). All 18 filiform SAs were located in the left colon, including 15 (83%) that occurred in the rectum, compared with 43% of the control group (P=0.03). Filiform SAs were also larger (1.6 cm) than SAs (mean: 1.2 cm, P=0.02), but no other clinical differences were noted. Most (56%) filiform SAs contained marked stromal edema and tall nonmucinous cells with abundant eosinophilic cytoplasm (61%). High-grade dysplasia was present in 4/18 (22%) cases. Four (22%) filiform SAs also contained nonserrated adenomatous elements with a villous (3 cases) or tubular (1 case) growth pattern. Two (11%) cases contained adjacent areas of sessile SAs and 4 (22%) had hyperplastic areas. None of the polyps in the control group showed stromal edema, high-grade dysplasia, or mixed elements. Polyps in both groups demonstrated comparable staining patterns for O6-methylguanine methyltransferase, MLH-1, MSH-2, CDX2, β-catenin, and Ki-67, and none showed increased nuclear p53 expression. Low-frequency microsatellite instability was present in 5/12 (42%) filiform SAs, 7/12 (58%) were microsatellite stable. Mitogen-activated protein kinase pathway abnormalities were present in 71% of the cases [7/14 (50%) with BRAF and 3/14 (21%) with K-ras mutations]. Four cases showed silent p53 mutations upon direct sequencing and 4 revealed loss of heterozygosity at the loci evaluated, including 1 at D5S346 [adenomatous polyposis coli (APC) gene], 1 at D17S250 (p53 gene), and 2 at MYCL (chromosome 1p34). We conclude that filiform SA potentially represents an unusual variant of SA with a predilection for the left colon, particularly the rectum.