结直肠锯齿状腺瘤的临床特征及恶变影响因素分析

目的锯齿状腺瘤被公认为结直肠癌的癌前病变,锯齿状通路被认为是可以独立发展成结直肠癌的重要通路,但目前对于锯齿状腺瘤恶变的相关危险因素还知之甚少。本文旨在分析锯齿状腺瘤在结直肠中的分布特点及潜在恶变因素。方法采用病例对照研究方法,回顾性收集2017年4月至2019年7月期间在中国医学科学院肿瘤医院行肠镜检查并经病理诊断为锯齿状腺瘤患者的临床资料,排除同时具有两种及以上病理类型病变的患者。总结锯齿状腺瘤的临床特征,并进行单因素和Logistic多因素回归分析,探讨锯齿状腺瘤发生恶变的影响因素。结果共在28730例行肠镜检查患者中,发现311例(1.08%)锯齿状腺瘤患者,共发现锯齿状腺瘤372枚。按WHO分类,无蒂锯齿状腺瘤/息肉22枚(5.9%),传统锯齿状腺瘤84枚(22.6%),未分类锯齿状腺瘤266枚(71.5%)。病理结果显示:无异型增生病变106枚(28.5%),低级别上皮内瘤变病变228枚(61.3%),高级别上皮内瘤变或癌变38枚(10.2%)。病变长径<10 mm有204枚(54.8%),≥10 mm有168枚(45.2%);病变位于左半结直肠238枚(64.0%),右半结肠134枚(36.0%)。内镜下大体分型:扁平型16枚(4.3%),无蒂型174枚(46.8%),亚蒂型117枚(31.5%),带蒂型59枚(15.9%)。窄带成像国际结直肠内镜(NICE)分型:Ⅰ型85枚(22.8%),Ⅱ型280枚(75.3%),Ⅲ型4枚(1.1%)。单因素分析显示,病变大小、病变位置、病变部位及不同WHO分类与结直肠锯齿状腺瘤发生恶变有关(均P<0.05);不同NICE分型的锯齿状腺瘤,其恶变率的差异亦有统计学差异(P=0.001)。多因素分析结果显示,病变长径≥10 mm(OR=6.699,95%CI:2.843~15.786)以及病变位于左半结直肠(OR=2.657,95%CI:1.042~6.775)是结直肠锯齿状腺瘤发生恶变的独立危险因素。结论锯齿状腺瘤主要位于左半结直肠,当病变长径≥10 mm或病变位于左半结直肠时,易发生恶变。     

Ki-67蛋白和p53蛋白在肝胆管上皮内瘤变及癌变诊断中的意义

目的：研究增殖指标Ki-67蛋白和p53蛋白在人肝胆管上皮内瘤变及癌变中的表达及其诊断意义。
方法：运用免疫组织化学S-P方法检测70例肝胆管上皮内瘤变及癌变（低级别肝胆管上皮内瘤变42例,高级别上皮内瘤变28例,高级别中癌变16例）组织中Ki-67蛋白和p53蛋白的表达情况。
结果：（1）肝胆管上皮癌变组织中Ki-67的增殖指数为20.65±7.62,明显高于肝胆管上皮内瘤变（P＜0.05）,并随肝胆管上皮增生程度的增加其增值指数也增高。（2）在16例肝胆管癌变组织中p53蛋白的增值指数为14.73±5.57,明显高于胆管上皮内瘤变组织的蛋白表达（P＜0.05）。
结论：从肝胆管上皮内瘤变到癌变这一发展过程中,Ki-67及p53蛋白增值指数随着细胞增生程度而增高,为临床判断病变程度提供了较具体可靠的参考依据。

     

内镜下结直肠锯齿状病变的临床特征

结直肠癌在我国其发病率和病死率呈逐年上升趋势,故对结直肠癌前病变的早期诊断具有重要临床意义。结直肠锯齿状病变是近年来才被证实的一类新的结直肠癌前病变。2010年,WHO消化系统肿瘤分类对锯齿状病变做了明确定义,并对分类及诊断标准做了详细介绍［1］。将其定义为一组以上皮锯齿状结构为特征的病变,包括增生性息肉（HP）、无蒂锯齿状腺瘤（息肉）（SSA／P）及传统锯齿状腺瘤（TSA）;并在结直肠癌亚型中分出锯齿状腺癌（serrated adenocarcinoma,SAC）。一般认为,HP为良性病变,SSA／P和TSA是锯齿状癌前病变,可通过锯齿状分子遗传学及表观遗传学途径发生癌变,最终发展为锯齿状腺癌。     

hMLH1在直肠上皮内瘤变和早期直肠癌组织中的表达

目的探讨hMLH1在直肠上皮内瘤变与早期直肠癌组织中的表达情况及其早期诊断价值。方法采用PV-9000二步法免疫组织化学检测技术对术后确诊的28例早期浸润性直肠癌、36例直肠上皮内瘤变和30例正常直肠黏膜组织的石蜡切片进行hMLHl蛋白表达的检测。结果正常直肠黏膜组织、直肠上皮内瘤变组织和早期浸润性直肠癌组织hMLH1蛋白的阳性表达率分别为100％（30／30）、77．8％（28／36）和39．3％（11／28），3组比较差异有统计学意义（P〈0．05）。直肠上皮内瘤变组织hMLH1的阳性表达与患者的年龄、性别、肿瘤最大径、异型增生、肿瘤类型和距肛缘的距离均无关（P〉0．05）；早期直肠癌组织hMLH1阳性表达与其分化程度有关（P〈0．05）。结论hMLHI基因表达缺失可能是直肠癌发生的早期事件之一,hMLH1蛋白检测对于上皮内瘤变和早期直肠癌中两种疾病的早期诊断有一定的临床价值。     

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目的 探讨结直肠上皮内瘤变病理诊断的临床意义和外科治疗的原则.方法 江苏大学附属上海第八医院于2004年1月至20C16年12月共收治术前经内镜活检,病理诊断为"上皮内瘤变"的病例共96例,其中诊断为低级别上皮内瘤变47例,高级别上皮内瘤变49例.行腺瘤切除术2例,根治性结肠切除手术31例,直肠低位前切除术43例,经肛门局部切除术10例,Hartmann直肠经腹切除结肠造口术1例,腹会阴切除术2例,Parks结肠肛管吻合术7例.结果 术后62例(64.58%)病理证实为浸润性腺癌,49例术前诊断为高级别上皮内瘤变的腺瘤中89.80%术后病理是腺癌.在低级别上皮内瘤中亦有38.29%的浸润性癌.在62例腺癌中1例伴有肝转移,2例有邻近组织转移,术后病理证实有局部淋巴结转移或见癌结节17例(17/62,27.4%).结论 要重视结直肠上皮内瘤变的病理诊断,高度警惕高级别上皮内瘤变实际为浸润性癌的可能性极大,如果肿瘤的位置不涉及保肛的问题,宜首选作病变肠段切除,如术中可确诊为浸润性癌,则应行根治性切除手术.     

内镜黏膜切除术治疗消化道无蒂及亚蒂息肉

目的探讨内镜黏膜切除术（endoscopic mucosal resection,EMR）治疗消化道无蒂及亚蒂息肉的安全性及效果。方法 2010年6月～2012年4月,胃息肉85例（88枚）、大肠息肉62例（113枚）,直径〈1.0 cm 95枚,1.0～2.0 cm 101枚,2.0～3.5 cm 5枚;无蒂72枚,亚蒂129枚。最多一例为5枚。采用黏膜下注射-切除法治疗直径〈2.0 cm的无蒂或亚蒂胃、大肠息肉;透明帽负压吸引切除（EMR-C）治疗直径〉2.0 cm的无蒂胃息肉,圈套困难的直径〈2.0 cm的无蒂及亚蒂胃息肉;分片黏膜切除术（endoscopic picemeal mucosal resection,EPMR）治疗直径〉2.0 cm的亚蒂胃息肉,直径〉2.0 cm的无蒂、亚蒂大肠息肉。结果 1枚胃窦部扁平息肉行EMR-C;5枚直径〉2.5 cm的大肠亚蒂、无蒂息肉行EPMR;其余均行黏膜下注射-切除法。术中、术后无出血、穿孔。术后病理检查增生性息肉69枚,管状腺瘤64枚,炎性息肉47枚,管状绒毛状腺瘤10枚,绒毛状腺瘤5枚,锯齿状腺瘤2枚,腺瘤伴高级别上皮内瘤变2例（2枚）,腺瘤伴局部癌变2例（2枚）。腺瘤伴高级别上皮内瘤变的2例中,1例行肠段切除术,术后病理检查未见病变残留;1例EMR术后6个月未复查。腺瘤伴局部癌变的2例中,1例即行结肠癌根治术,术后病理直肠黏膜局部缺损,未见病变残留,区域淋巴结转移癌;1例拒绝手术,亦未复查。16例胃息肉及10例肠息肉术后1年内镜复查,2例肠息肉术后2年肠镜复查,均未见息肉复发。结论采用EMR治疗无蒂和亚蒂息肉安全、有效。     

结直肠上皮内瘤变的诊断意义与处理原则

目的 探讨结直肠上皮内瘤变病理诊断的临床意义和外科治疗的原则.方法 于2004年1月至2008年6月共收治术前经内镜活检、病理诊断为"上皮内瘤变"的病例共158例(共162个肿瘤),其中诊断为低级别上皮内瘤变73例,高级别上皮内瘤变89例.行腺瘤切除术5例,根治性结肠切除手术49例,直肠低位前切除术74例,经肛门局部切除术16例,Hartmann直肠经腹切除结肠造口术2例,腹会阴切除术4例,Parks结肠肛管吻合术7例,乙结肠造口术1例.经手术切除的标本常规作病理学检查,并与该患者的术前活检作比较,进行回顾性分析.结果 术后109例(67.3%)病理证实为浸润性腺癌,在89例术前诊断为高级别上皮内瘤变的腺瘤中,80例(89.9%)术后病理确定是腺癌;在低级别上皮内瘤变中亦有29例(39.7%)术后确定为浸润性腺癌.在109例腺癌中2例伴有肝转移(MI),18例则有邻近组织浸润(T4).术后病理证实有局部淋巴结转移或见癌结节者26例(23.9%).结论 应重视结直肠上皮内瘤变的病理诊断,高度警惕高级别上皮内瘤变.在临床和内镜中疑为恶性的病变,若不涉及保肛问题,宜首选作病变肠段切除,如术中可确诊为浸润性癌,则应作根治性切除.     

结直肠上皮内瘤变的诊断意义与处理原则

目的 探讨结直肠上皮内瘤变病理诊断的临床意义和外科治疗的原则.方法 于2004年1月至2008年6月共收治术前经内镜活检、病理诊断为"上皮内瘤变"的病例共158例(共162个肿瘤),其中诊断为低级别上皮内瘤变73例,高级别上皮内瘤变89例.行腺瘤切除术5例,根治性结肠切除手术49例,直肠低位前切除术74例,经肛门局部切除术16例,Hartmann直肠经腹切除结肠造口术2例,腹会阴切除术4例,Parks结肠肛管吻合术7例,乙结肠造口术1例.经手术切除的标本常规作病理学检查,并与该患者的术前活检作比较,进行回顾性分析.结果 术后109例(67.3%)病理证实为浸润性腺癌,在89例术前诊断为高级别上皮内瘤变的腺瘤中,80例(89.9%)术后病理确定是腺癌;在低级别上皮内瘤变中亦有29例(39.7%)术后确定为浸润性腺癌.在109例腺癌中2例伴有肝转移(MI),18例则有邻近组织浸润(T4).术后病理证实有局部淋巴结转移或见癌结节者26例(23.9%).结论 应重视结直肠上皮内瘤变的病理诊断,高度警惕高级别上皮内瘤变.在临床和内镜中疑为恶性的病变,若不涉及保肛问题,宜首选作病变肠段切除,如术中可确诊为浸润性癌,则应作根治性切除.     

结直肠上皮内瘤变的诊断意义与处理原则

目的 探讨结直肠上皮内瘤变病理诊断的临床意义和外科治疗的原则.方法 于2004年1月至2008年6月共收治术前经内镜活检、病理诊断为"上皮内瘤变"的病例共158例(共162个肿瘤),其中诊断为低级别上皮内瘤变73例,高级别上皮内瘤变89例.行腺瘤切除术5例,根治性结肠切除手术49例,直肠低位前切除术74例,经肛门局部切除术16例,Hartmann直肠经腹切除结肠造口术2例,腹会阴切除术4例,Parks结肠肛管吻合术7例,乙结肠造口术1例.经手术切除的标本常规作病理学检查,并与该患者的术前活检作比较,进行回顾性分析.结果 术后109例(67.3%)病理证实为浸润性腺癌,在89例术前诊断为高级别上皮内瘤变的腺瘤中,80例(89.9%)术后病理确定是腺癌;在低级别上皮内瘤变中亦有29例(39.7%)术后确定为浸润性腺癌.在109例腺癌中2例伴有肝转移(MI),18例则有邻近组织浸润(T4).术后病理证实有局部淋巴结转移或见癌结节者26例(23.9%).结论 应重视结直肠上皮内瘤变的病理诊断,高度警惕高级别上皮内瘤变.在临床和内镜中疑为恶性的病变,若不涉及保肛问题,宜首选作病变肠段切除,如术中可确诊为浸润性癌,则应作根治性切除.     

结直肠上皮内瘤变的诊断意义与处理原则

目的 探讨结直肠上皮内瘤变病理诊断的临床意义和外科治疗的原则.方法 于2004年1月至2008年6月共收治术前经内镜活检、病理诊断为"上皮内瘤变"的病例共158例(共162个肿瘤),其中诊断为低级别上皮内瘤变73例,高级别上皮内瘤变89例.行腺瘤切除术5例,根治性结肠切除手术49例,直肠低位前切除术74例,经肛门局部切除术16例,Hartmann直肠经腹切除结肠造口术2例,腹会阴切除术4例,Parks结肠肛管吻合术7例,乙结肠造口术1例.经手术切除的标本常规作病理学检查,并与该患者的术前活检作比较,进行回顾性分析.结果 术后109例(67.3%)病理证实为浸润性腺癌,在89例术前诊断为高级别上皮内瘤变的腺瘤中,80例(89.9%)术后病理确定是腺癌;在低级别上皮内瘤变中亦有29例(39.7%)术后确定为浸润性腺癌.在109例腺癌中2例伴有肝转移(MI),18例则有邻近组织浸润(T4).术后病理证实有局部淋巴结转移或见癌结节者26例(23.9%).结论 应重视结直肠上皮内瘤变的病理诊断,高度警惕高级别上皮内瘤变.在临床和内镜中疑为恶性的病变,若不涉及保肛问题,宜首选作病变肠段切除,如术中可确诊为浸润性癌,则应作根治性切除.     

结直肠无蒂锯齿状病变的特征和临床问题

无蒂锯齿状息肉/腺瘤（SSL）曾经被认为是良性病变,而现有研究表明,通过锯齿状瘤变途径,约15%～30%的SSL最终发展为结直肠癌。锯齿状息肉分为增生性息肉、无蒂锯齿状病变、伴发育不良的无蒂锯齿性病变、传统锯齿状腺瘤和未分类锯齿状腺瘤,每一种都具有不同的形态学和分子特征。尽管对SSL的理解有所提高,但由于频繁的病理错误分类、结肠内镜检测不足和不完全切除率高,SSL仍然是内镜和病理医生面临的诸多临床挑战。本文总结了目前对锯齿状息肉的新认识和诊断问题。     

IGF-Ⅱ和IGF-ⅠR及IGFBP-3在结直肠癌组织中的表达及其临床意义

目的 :检测IGF-Ⅱ、IGF-ⅠR、IGFBP-3在结直肠癌中的表达,探讨其表达在结直肠癌的早期诊断中的价值。方法:应用免疫组织化学SP法分别检测结直肠癌、结直肠腺瘤、炎性息肉及正常结肠黏膜组织中IGF-Ⅱ、IGF-ⅠR、IGFBP3的表达情况。结果:1)IGF-Ⅱ、IGF-ⅠR、IGFBP-3在结直肠癌组织中表达的阳性率均高于结直肠腺瘤、炎性息肉和正常组织,且具有统计学意义(P<0.05);2)IGF-Ⅱ、IGF-ⅠR、IGFBP-3在炎性息肉和管状腺瘤、混合型腺瘤及绒毛状腺瘤中表达阳性率依次增高,但差异无统计学意义(P>0.05);3)IGF-Ⅱ、IGF-ⅠR、IGFBP-3与患者的年龄、性别、吸烟情况、有无饮酒史及肿瘤家族史等指标之间均无统计学意义(P>0.05);4)IGF-Ⅱ、IGF-ⅠR、IGFBP-3间的表达呈正相关。结论:结直肠癌患者血清IGF-Ⅱ、IGF-ⅠR、IGFBP-3水平明显升高可能与结直肠癌的发生相关。     

Apoptosis index and apoptosis-related antigen expression in serrated adenoma of the colorectum: the saw-toothed structure may be related to inhibition of apoptosis.

Serrated adenoma of the colorectum is a recently proposed entity characterized by a saw-toothed structure of hyperplastic polyp and cytologic atypia of tubular adenoma. To clarify the role of apoptosis in morphogenesis of serrated adenoma, we investigated apoptotic indices and expression of apoptosis-related antigens in the tumor cells. Thirty-eight serrated adenomas were examined by the nick-end DNA labeling method and immunostained for CD95 (Fas), bcl-2, bax, and p53. Thirty-seven hyperplastic polyps, 48 tubular adenomas, and 16 sections containing normal colonic mucosa were similarly examined for comparison. The apoptotic indices in the upper and middle zones of the crypts of serrated adenomas and hyperplastic polyps were lower than those of normal colon mucosa and tubular adenomas with statistically significant differences. The CD95 expression was diffusely observed throughout the epithelium of normal crypts and tubular adenomas, whereas it was reduced in serrated adenomas and hyperplastic polyps. The bcl-2 expression was confined to the basal crypts in the latter two lesions but was diffuse throughout the neoplastic epithelium in tubular adenomas. The bax expression was increased in serrated adenomas and tubular adenomas but was decreased in hyperplastic polyps. Overexpression of p53 protein was observed in 50% of serrated adenomas, none of hyperplastic polyps, and 14% of tubular adenomas. These findings suggest that inhibition of apoptosis is caused by reduced CD95 expression in serrated adenomas and hyperplastic polyps, which may induce the characteristic saw-toothed structure in these lesions. Based on the similarities and differences between serrated adenoma and hyperplastic polyp observed in the present study, a progression from the latter to the former lesion may be postulated.     

Hyperplastic polyposis: association with colorectal cancer

Hyperplastic polyposis is a loosely defined syndrome initially thought not to confer a clinically important predisposition to colorectal cancer. The aim of the current study was to examine the clinical, histologic, and molecular features of a prospective series of cases meeting a strict definition of the condition. Twelve patients were identified, seven of whom had developed colorectal cancer. Most polyps were hyperplastic, but 11 patients also had polyps containing dysplasia as either serrated adenomas. mixed polyps, or traditional adenomas. The mean percentage of dysplastic polyps in patients with cancer was 35%, and in patients without cancer, 11% (p < 0.05). Microsatellite instability (MSI) was present in 3 of 47 hyperplastic polyps and two of eight serrated adenomas. Kras was mutated in 8 of 47 hyperplastic polyps and two of eight serrated adenomas. No polyps showed loss of heterozygosity of chromosomes 5q, 1p, or 18q. Two of seven cancers showed a high level of MSI. It is concluded that hyperplastic polyposis is associated with a high risk of colorectal cancer. Hyperplastic polyps are the dominant type of polyp, but most cases have some dysplastic epithelium. A higher proportion of dysplastic polyps is associated with increased cancer risk. Clonal genetic changes are observed in some hyperplastic polyps and serrated adenomas.     

细胞增殖标记物MCM2在结直肠腺瘤的表达差异及意义

目的探讨细胞增殖标记物微小染色体支持蛋白2（MCM2）在结直肠腺瘤中的表达及MCM2的表达差异与不同临床病理特征的关系。方法应用免疫组化SP法检测MCM2在结直肠腺瘤中的表达部位;应用实时荧光定量PCR法检测MCM2 mRNA在112例结直肠腺瘤中表达量的差异,同时用REST-XL软件分析不同临床病理特征的结肠腺瘤之间MCM2的表达差异及其意义。结果 MCM2在结直肠腺瘤呈全层上皮表达,MCM2 mRNA表达与结直肠腺瘤患者的年龄和腺瘤直径、形态及组织病理类型无关,不同腺瘤间不典型增生程度与MCM2 mRNA表达量有显著差异性（P〈0.05）。结论细胞增殖标记物MCM2在结直肠腺瘤表达与腺瘤不典型增生程度相关,可能作为早期筛查诊断结肠癌及评估腺瘤突变的指标之一。     

Twist 蛋白在结直肠癌和肝转移组织中的表达及临床意义

目的：探讨Twist蛋白在结直肠癌及肝转移组织中的表达及其临床意义。方法选取2001年1月至2012年12月伴有肝转移的结直肠癌患者成套组织标本（原发灶、肝转移灶、距肿瘤边缘10 cm以上的正常结直肠黏膜组织）54例患者。采用免疫组织化学SP法检测54例患者标本的原发灶、肝转移灶及正常结直肠黏膜组织中Twist蛋白的表达,数据分析处理采用SPSS 19．0统计软件包,计数资料采用R ＆#215;C表资料的χ2检验,生存分析采用Kaplan-Meier生存曲线法,Log-rank检验分析肿瘤浸润程度、淋巴结转移、组织学分型及Twist蛋白在原发灶及肝转移灶中表达的情况,采用Cox回归模型进行独立预后因素分析。结果 Twist蛋白在结直肠癌原发灶中的阳性表达率明显高于肝转移灶、正常结直肠黏膜组织（P＜0．001）;原发灶中Twist蛋白在不同浸润深度T2、T3、T4的阳性表达率分别为30．0％、64．9％、85．7％,其差异有统计学意义（P＝0．049）;单因素分析显示,原发灶及肝转移灶中Twist蛋白阳性表达组患者的总体生存率均显著低于阴性表达组（P＝0．034,P＝0．031）;多因素生存分析证实肿瘤浸润深度、淋巴结转移和肿瘤组织学分型为影响患者总体生存率的独立因素（P＜0．001,P＝0．002,P＝0．005）,而Twist蛋白在原发灶及肝转移灶中的表达不是总体生存率的独立因素（ P＝0．548,P＝0．742）。结论 Twist蛋白在结直肠癌肝转移患者的原发灶高表达,其可能参与结直肠癌肝转移的发生,对评价结直肠癌肝转移患者预后具有一定临床意义。     

Phenotype and polyp landscape in serrated polyposis syndrome: a series of 100 patients from genetics clinics

Serrated polyposis syndrome (SPS), also known as hyperplastic polyposis, is a syndrome of unknown genetic basis defined by the occurrence of multiple serrated polyps in the large intestine and associated with an increased risk of colorectal cancer (CRC). There are a variety of SPS presentations, which may encompass a continuum of phenotypes modified by environmental and genetic factors. To explore the phenotype of SPS, we recorded the histologic and molecular characteristics of multiple colorectal polyps in patients with SPS recruited between 2000 and 2010 from genetics clinics in Australia, New Zealand, Canada, and the United States. Three specialist gastrointestinal pathologists reviewed the polyps, which they classified into conventional adenomas or serrated polyps, with various subtypes, according to the current World Health Organization criteria. Mutations in BRAF and KRAS and mismatch repair protein expression were determined in a subset of polyps. A total of 100 patients were selected for the study, of whom 58 were female and 42 were male. The total polyp count per patient ranged from 6 to 150 (median 30). The vast majority of patients (89%) had polyposis affecting the entire large intestine. From this cohort, 406 polyps were reviewed. Most of the polyps (83%) were serrated polyps: microvesicular hyperplastic polyps (HP) (n=156), goblet cell HP (n=25), sessile serrated adenoma/polyps (SSA/P) (n=110), SSA/P with cytologic dysplasia (n=28), and traditional serrated adenomas (n=18). A further 69 polyps were conventional adenomas. BRAF mutation was mainly detected in SSA/P with dysplasia (95%), SSA/P (85%), microvesicular HP (76%), and traditional serrated adenoma (54%), whereas KRAS mutation was present mainly in goblet cell HP (50%) and in tubulovillous adenoma (45%). Four of 6 SSA/Ps with high-grade dysplasia showed loss of MLH1/PMS2 expression. CRC was diagnosed in 39 patients who were more often found to have a conventional adenoma compared with patients without CRC (P=0.003). Patients with SPS referred to genetics clinics had a pancolonic disease with a high polyp burden and a high rate of BRAF mutation. The occurrence of CRC was associated with the presence of conventional adenoma.     

Morphologic reappraisal of serrated colorectal polyps

The "hyperplastic polyp" is considered a benign lesion with no malignant potential, whereas "serrated adenoma" is a precursor of adenocarcinoma. The morphologic complexity of the serrated adenoma varies from being clearly adenomatous to being difficult to distinguish from hyperplastic polyp, which creates a need for more detailed morphologic analysis of all serrated polyps. We evaluated 24 morphologic variables in 289 serrated polyps from the colon and rectum. Cluster analysis and discriminant analysis were performed. A subset of polyps was immunostained for hMLH1 and hMSH2. Major differences were found between right-sided and left-sided polyps. A distinct group of serrated polyps with abnormal proliferation was identified throughout the colon and rectum. These polyps demonstrated decreased expression of hMHL1 and hMSH2 compared with polyps with normal proliferation. Left-sided serrated polyps with normal proliferation further clustered into three groups: vesicular cell-type, goblet cell-type, and mucin-poor-type. We recommend evaluation of the localization, size, and morphologic features when serrated polyps are included in colorectal carcinogenesis research. Polyps with abnormal proliferation are similar to the polyps in "hyperplastic polyposis" and, because of their decreased expression of hMLH1 and hMSH2, may be the subset of polyps associated with the development of colorectal carcinoma via the microsatellite instability pathway.