结直肠锯齿状腺瘤内镜和病理形态特征分析

目的 探讨锯齿状腺瘤（SA）内镜下形态和病理组织学特征.方法 回顾分析南方医院消化内镜中心2002年1月至2005年7月检出的大肠息肉病例,了解SA的检出率、内镜形态、腺管开口分型和病理组织学特征.结果 11894例肠镜检查共检出息肉病例1928例（2811枚）,检出率为16.21%,其中SA 61例（71枚）,检出率为0.51%,占息肉构成比为3.16%.SA直径＞1 cm者占39.44%,明显大于增生性息肉;内镜下表现为有蒂息肉所占的比例（26.76%）高于增生性息肉（13.25%）,但低于腺瘤性息肉（43.95%）.1815枚息肉进行腺管开口分型,SA多表现为Ⅲ型腺管开口（41.67%）,部分表现为Ⅳ型腺管开口（18.33%）,与腺瘤性息肉较接近.SA中度以上异型增生发生率介于管状腺瘤和绒毛状腺瘤之间,并有2.82%的癌变率.结论 SA内镜形态、腺管开口分型和病理学特点提示其本质上与增生性息肉不同,与肿瘤性息肉表现类似,具有恶变潜能.     

结直肠锯齿状腺瘤内镜表现和病理学特征分析

目的探讨锯齿状腺瘤（SA）内镜下表现和病理学特征。方法回顾分析滨州医学院附属医院2000年1月～2008年5月检出的大肠息肉病例,了解SA的检出率、内镜形态和病理学特征。结果8726例肠镜检查共检出大肠息肉1062例（1457枚）,检出率为12．17％,其中SA32例（60枚）,检出率为0．37％,占息肉构成比为3．01％。SA直径〉1cm者占21．63％,明显大于增生性息肉（8．57％）;SA表现为有蒂息肉所占的比例（8．33％）略高于增生性息肉（5．71％）,但都低于腺瘤性息肉（40．84％）。SA癌变率介于管状腺瘤和绒毛状腺瘤之间,接近于管状绒毛状腺瘤。结论SA内镜形态、病理学特点提示SA是兼有增生性息肉形态学特征和腺瘤性息肉组织学特点的息肉,具有恶变潜能.     

窄带成像放大内镜鉴别大肠肿瘤性与非肿瘤性病变的价值

目的 探讨窄带成像放大内镜（NBI—ME）鉴别大肠肿瘤性与非肿瘤性病变表面网状微血管结构改变的临床价值。方法选择常规内镜检出大肠肿瘤性、非肿瘤性病变144处（102例）,记录NBI—ME观察病变表面微血管结构（CP）形态和染色放大内镜观察病变黏膜表面腺管开口（pit）形态。分析pit周围CP形态变化,比较两者形态间的关系。所有病变经内镜或手术治疗后行组织病理学检查。结果常规内镜鉴别病变是否为肿瘤性的准确率75．7％、敏感性85．1％、特异性40．0％,明显低于NBI—ME和染色放大内镜（P〈0．005）,NBI—ME和染色放大内镜间则未见差异。CP分型与pit分型对照,CP—Ⅰ型、Ⅱ型、Ⅳ型、Ⅵa型分别与pitⅠ型、Ⅱ型、Ⅳ型、Ⅴ1型间一致性达100％。144处病变中,内镜治疗129处,手术治疗15处。组织病理学检查：非肿瘤性30处（增生性息肉17处、炎症性息肉13处）;肿瘤性114处（腺瘤95处、腺癌19处）。结论初步显示NBI—ME和染色放大内镜之间具有正相关性,两种检查方法互补可作为当前鉴别大肠病变是否为肿瘤性的重要手段。     

大肠腺管开口分型的超微结构研究

目的通过对大肠息肉的超微结构观察,分析其表面腺管开口形态（pit pattern）的演化过程与息肉性质发生改变的关系。方法对50例大肠息肉患者行结肠放大内镜检查,结合内镜下黏膜染色对病灶行pit pattern分型,内镜或手术切除病灶,所有样本分别行组织病理学分析、扫描及透射电镜观察。结果本组50例样本,pit pattern记录Ⅰ型10个、Ⅱ型8个、Ⅲ型15个、Ⅳ型9个、Ⅴ型5个、混合型3个。组织学诊断验证其阳性预测准确率达86％（43／50）,鉴别腺瘤性息肉的准确率达94％（30／32）。扫描电镜下Ⅰ、Ⅱ型隐窝规则洞状,隐窝周围细胞大小一致,吸收细胞微绒毛多,杯状细胞丰富;Ⅲ、Ⅳ、Ⅴ型隐窝逐渐变形,表面细胞及组织异型程度不断加重。透射电镜下Ⅰ、Ⅱ型腺上皮细胞排列整齐,连接紧密,腔面微绒毛规则,胞浆线粒体、内质网丰富,核卵圆形位于基底部,基底膜平滑连续;Ⅲ、Ⅳ、Ⅴ型腺上皮细胞绒毛逐渐稀疏紊乱,胞浆线粒体肿胀,内质网扩张,溶酶体数量增加,核异型、核分裂明显加重,基板逐渐出现中断或消失。结论pit pattern的变化受大肠隐窝表面细胞的形态、比例以及构成等因素的影响,腺上皮细胞的超微结构变化是pit pattern形态和息肉性质发生改变的物质基础。     

内镜智能分光比色放大内镜对胃息肉的诊断价值

[目的]探讨内镜智能分光比色技术(FICE)染色放大内镜对胃息肉的诊断价值。[方法]回顾性分析FICE染色放大内镜下178枚胃息肉的腺管开口分型,将FICE染色放大内镜诊断与病理结果进行对比。[结果]178枚息肉中,胃底40枚,胃体75枚,胃窦63枚。腺管开口Ⅰ型53枚,Ⅱ型74枚、ⅢL型34枚、Ⅲs型6枚,Ⅳ型10枚、Ⅴi型1枚。病理结果提示炎性息肉多为Ⅰ型,少数为Ⅱ型和ⅢL型,增生性息肉主要为Ⅱ型,胃底腺息肉主要为Ⅲl型,腺瘤性息肉主要为Ⅳ型。[结论]FICE染色放大内镜诊断胃息肉与病理诊断符合率高,可有效拟诊胃息肉性质,为胃息肉的治疗提供参考依据。     

大肠黏膜腺管开口分型对早期大肠癌的诊断价值

目的 评价腺管开口分型对诊断早期大肠癌及癌前病变的临床实用价值。方法 2000年11月～2002年8月结肠镜检查4176例次，采用内镜下黏膜染色技术，部分病变结合放大内镜及实体显微镜观察腺管开口分型(pit分型)并与病理诊断对照，pit分型采用工藤分型。结果 752例患者发现大肠隆起、扁平等不同病变共955个，共检出早期大肠癌14例，进展期癌209例，Ⅱa、Ⅱb、Ⅱc、Ⅱa Ⅱc病变76个。侧向发育型肿瘤(LST型)病变43个，直径16～110mm，其中Ⅱ型2个，ⅢL18个，Ⅳ19个，ⅤA型1个，ⅤN型3个。非肿瘤性息肉以Ⅰ、Ⅱ型腺管开口为主，占85．4％(303／355)；而腺瘤性息肉则以Ⅲ、Ⅳ型腺管开口为主，占86．0％(504／586)；进展期癌均表现为黏膜腺管开口破坏无结构，为ⅤN型；14例早期癌中有8例腺管开口为Ⅴ型，其中ⅤA型2个，ⅤN型6个。结论 大肠腺管开口分型对于判断肿瘤性、非肿瘤性病变以及早期大肠癌并指导及时的内镜治疗或手术切除具有重要意义及临床实用价值。     

大肠锯齿状腺瘤7例报告

大肠的锯齿状腺瘤指大肠的一类特殊病理形态的腺瘤,其成瘤上皮成分有明显增生,使腺管或绒毛呈现锯齿状外观,类似于增生性息肉样改变,或腺瘤成分与增生性息肉成分同时存在。1990年Longacre TA报告了110例这种形态的腺瘤,并将其命名为混合型增生性腺瘤样息肉／Serrated腺瘤,后被简称为Serrated腺瘤即锯齿状腺瘤。     

智能染色内镜对早期大肠癌及其癌前病变的诊断价值

目的评价富士能智能电子分光技术（FICE）结合放大内镜在早期大肠癌诊断中的价值。方法2010年1月至2011年12月经普通内镜发现存在大肠黏膜可疑病灶且符合研究要求的患者共325例,行FICE结合放大内镜及靛胭脂染色检查,部分病变结合放大内镜及实体显微镜观察腺管开口分型（pit分型）并与病理诊断对照,pit分型采用工藤分型。结果396个病变中非肿瘤性病变占13．6％（544396）;各类腺瘤占76．0％（301／396）,其中3例腺瘤恶变,占腺瘤的1．0％（3／301）;进展期肠癌41例,占10．4％（41／301）。上述病变黏膜腺管开口类型分析显示在非肿瘤性病变中尤其增生性病变、炎性息肉绝大部分为Ⅰ、Ⅱ型腺管开口,占92．7％（38／41）。在肿瘤性病变中,管状腺瘤及管状绒毛腺瘤之腺管开口以Ⅲ。型为主,而绒毛状腺瘤则以Ⅳ型为多见。在进展期癌中,无1例外地表现为腺管开口的破坏。甚至无腺管结构。将FICE结合放大内镜及靛胭脂染色检查结果及病理检查结果进行统计得出：FICE结合放大内镜诊断早期大肠癌的诊断符合率、敏感性、特异性、假阳性率、假阴性率分别为97．8％（361D96）、92．6％（38／41）、99．4％（353／355）、92．6％（38／41）、99．4％（353／355）：靛胭脂染色诊断早期大肠癌的诊断符合率、敏感性、特异性分别为97．7％（390／396）、87．8％（36／41）、98．9％（351／355）、1．12％（4／355）、12．3％（5／41）;二者比较差异均无统计学意义（P均〉0．05）。结论FICE结合放大内镜可以提供清晰的大肠黏膜血管图像,有助于早期大肠癌的诊断．可提高活检检查的准确性．与靛胭脂染色联用可提高早期大肠癌的诊断率。     

大肠侧向发育型肿瘤内镜下的诊断与治疗

目的探讨大肠侧向发育型肿瘤（LST）临床病理特征及内镜下黏膜切除术的有效性、安全性。方法经普通内镜检查发现LST 119例,染色后观察病灶大小及部位并进行形态分型,再结合放大内镜确定腺管开口类型。有治疗适应证者行内镜下黏膜切除术,切除病灶黏膜送病理检查。结果 28个月中共发现119例LST 124个病变。内镜下分型：颗粒均一型44个,结节混合型48个,平坦隆起型23个,假凹陷型9个。病变直径：10～20 mm 65个,21～30 mm 23个,31 mm以上36个,最大病变110 mm×100 mm。病变部位：直肠50个,乙状结肠25个,降结肠11个,横结肠10个,升结肠＋盲肠28个。黏膜腺管开口类型：Ⅲ型30个,其中17个为管状绒毛状腺瘤,12个为管状腺瘤;Ⅳ型56个,其中30个为绒毛状腺瘤,4个为黏膜内癌;Ⅴ型5个,其中2个为黏膜内癌,2个累及黏膜下层下1/3以下;Ⅱ型7个,其中5个为炎性增生性息肉,2个为锯齿状腺瘤（腺瘤性增生性息肉）：其余为ⅢL＋V型,其中23个为管状绒毛状腺瘤。符合适应证95例98个病变择期进行内镜下黏膜切除治疗,发生出血11例,均在操作过程中,无肠穿孔发生。结论大肠LST内镜形态具有一定特殊性,内镜下黏膜切除术是治疗在大肠的有效而安全的方法,可达到根治目的 。     

靛胭脂染色内镜检查对大肠微小腺瘤和息肉的诊断价值

目的探讨靛胭脂染色内镜检查在诊断大肠微小腺瘤和息肉中的价值。方法将31个大肠微小息肉分别行普通内镜及靛胭脂染色内镜检杏的结果与组织学检查结果比较,并比较2种内镜检查方法对大肠微小腺瘤和息肉的诊断准确率。结果靛胭脂染色内镜对大肠微小腺瘤和息肉的诊断准确率显著高于普通内镜,D组与A组、C组比较差异有娃著性（55．2％vs12％、10％）,P〈0．05;D组与B组比较差异无显著性i55．2％（腺瘤13．8％）VS50％（腺瘤10％）],P〉0．05。结论靛胭脂染色内镜检查可提高大肠微小腺瘤和息肉的诊断准确率。     

Clinicopathologic and endoscopic features of colorectal serrated adenoma: differences between polypoid and superficial types

BACKGROUND: Serrated adenoma is a distinct histologic colorectal lesion. There are two macroscopic types: polypoid and superficial. The aim of this study was to clarify clinicopathologic and endoscopic differences between polypoid and superficial serrated adenomas. METHODS: An analysis was conducted of the clinicopathologic and endoscopic features for 240 polypoid and 127 superficial serrated adenomas examined by colonoscopy, and the surface pit patterns of 114 polypoid and 64 superficial serrated adenomas examined by magnifying videoendoscopy. RESULTS: The male:female gender ratio for the polypoid serrated adenomas (3.5:1) was significantly higher than that for the superficial serrated adenomas (1.7:1). Superficial serrated adenomas were significantly larger than polypoid serrated adenomas (mean [standard deviation], respectively, 10.1 [7.9] mm vs. 6.3 [4.6] mm). In the distal segments of the colorectum, polypoid serrated adenomas were more common than superficial serrated adenomas. Granulonodular and lobular appearances at endoscopy were significantly more common for polypoid (23.3%) than for superficial serrated adenomas (7.1%). Pit patterns differed between the lesion types: polypoid serrated adenomas had type III(L) or IV pit patterns; all superficial serrated adenomas had the type II pit pattern. The relative frequency of occurrence of high-grade dysplasia and carcinoma in situ among superficial serrated adenomas (25.2%) was significantly greater than that among polypoid serrated adenomas (9.2%). The tubulovillous growth pattern was significantly more common in polypoid tumors (31.5%) than in superficial tumors (0%). CONCLUSIONS: Polypoid and superficial serrated adenomas have different clinicopathologic characteristics and growth patterns.     

Clinico-pathological aspects of colorectal serrated adenomas

AIM: To study the association of colorectal serrated adenomas (SAs) with invasive carcinoma, local recurrence, synchronicity and metachronicity of lesions. METHODS: A total of 4536 polyps from 1096 patients over an eight-year period (1987-1995) were retrospectively examined. Adenomas showing at least 50% of serrated architecture were called SAs by three reviewing pathologists. RESULTS: Ninety-one (2%) of all polyps were called SAs, which were found in 46 patients. Invasive carcinomas were seen in 3 out of 46 (6.4%) patients, of whom one was a case of familial adenomatous polyposis (FAR). A male preponderance was noted and features of a mild degree of dysplasia were seen in majority (n=75, 83%) of serrated adenomas. Follow-up ranged 1-12 years with a mean time of 5.75 years. Recurrences of SAs were seen in 3 (6.4%) cases, synchronous SAs in 16 (34.8%) cases and metachronous SAs in 9 (19.6%) cases. CONCLUSION: Invasive carcinoma arising in serrated adenoma is rare, accounting for 2 (4.3%) cases studied in this series.     

Emerging concepts in colorectal serrated polyps

Colorectal serrated polyps are heterogeneous epithelial lesions characterized by a serrated architecture. They include the classical hyperplastic polyps and the much rarer serrated adenomas and mixed polyps. Whereas serrated adenomas are composed of an unequivocal adenomatous epithelium with architectural serrated, mixed polyps include two separate hyperplastic and adenomatous components. During the past few years, another type of serrated polyp with only very subtle proliferation abnormalities has been described. These atypical serrated polyps may occur either sporadically or in the context of colorectal polyposis. Despite their close resemblance to traditional hyperplastic polyps, some authors argued that they should be regarded as authentically neoplastic lesions and have proposed to call them "sessile serrated adenomas". Their malignant potential requires their removal when discovered during colonoscopy. This article reviews the histological features, the endoscopic appearance, the natural history and the molecular phenotype of the different categories of serrated polyps and introduces the concept of "serrated neoplastic pathway" in the development of colorectal cancer.     

Serrated adenomas

Serrated adenomas are categorized as sessile serrated adenomas (SSAs) and traditional serrated adenomas (TSAs). SSAs are more prevalent in the proximal colon and lack classic dysplasia, whereas TSAs are more prevalent in the rectosigmoid and have cytologic dysplasia. Serrated adenomas may progress to colorectal adenocarcinoma through diverse molecular alterations. Colonoscopy is the only test for the early detection of serrated adenomas that allows inspection of the entire colon and same-session biopsy sampling or polypectomy, if necessary. If an endoscopic biopsy at the right colon reveals SSA without cytologic dysplasia or biopsy at the rectosigmoid reveals SSA or TSA, those polyps should be excised or surgically resected as necessary. Postpolypectomy surveillance for removed SSAs without dysplasia and TSAs must be performed at 5- and 3-year intervals, respectively, with colonoscopy to prevent recurrence and progression to colorectal adenocarcinoma.     

Molecular characteristics of serrated adenomas of the colorectum

BACKGROUND: Serrated adenomas (SAs) of the colorectum combine architectural features of hyperplastic polyps and cytological features of classical adenomas. Molecular studies comparing SAs and classical adenomas suggest that each may be a distinct entity; in particular, it has been proposed that microsatellite instability (MSI) distinguishes SAs from classical adenomas and that SAs and the colorectal cancers arising from them develop along a pathway driven by low level microsatellite instability (MSI-L). AIMS: To define the molecular characteristics of SAs of the colorectum. MATERIALS AND METHODS: We analysed 39 SAs from 27 patients, including eight SAs from patients with familial adenomatous polyposis (FAP). We screened these polyps for selected molecular changes, including loss of heterozygosity (LOH) close to APC (5q21) and CRAC1 (15q13-q22), MSI, and mutations of K-ras, APC, p53, and beta-catenin. Expression patterns of beta-catenin, p53, MLH1, MSH2, E-cadherin, and O(6)-methylguanine DNA methyltransferase (MGMT) were assessed by immunohistochemistry. Comparative genomic hybridisation was performed on several polyps. RESULTS: MSI was rare (<5% cases) and there was no loss of expression of mismatch repair proteins. Wnt pathway abnormalities (APC mutation/LOH, beta-catenin mutation/nuclear expression) occurred in 11 SAs, including 6/31 (19%) non-FAP tumours. CRAC1 LOH occurred in 23% of tumours. K-ras mutations and p53 mutations/overexpression were found in 15% and 8% of SAs, respectively. Loss of MGMT expression occurred in 18% of polyps and showed a borderline association with K-ras mutations. Aberrant E-cadherin expression was found in seven polyps. Comparative genomic hybridisation detected no gains or deletions of chromosomal material. CONCLUSIONS: The serrated pathway of colorectal tumorigenesis appears to be heterogeneous. In common with classical adenomas, some SAs develop along pathways involving changes in APC/beta-catenin. SAs rarely show MSI or any evidence of chromosomal-scale genetic instability. K-ras mutations may however be less common in SAs than in classical adenomas. Some SAs may harbour changes in the CRAC1 gene. Changes in known genes do not account for the growth of the majority of SAs.     

BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum

BACKGROUND AND AIMS: Mutations in BRAF have been linked with colorectal cancers (CRC) showing high level microsatellite instability (MSI-H). However, the distribution of BRAF mutations in MSI-H cancers remains to be clarified with respect to precursor lesions and the CpG island methylator phenotype (CIMP). METHODS: Forty three hyperplastic polyps (HP), nine mixed polyps (MP), five serrated adenomas (SA), 28 conventional adenomas (AD), 18 hereditary non-polyposis colorectal cancers (HNPCC), and 127 sporadic CRC (46 MSI-H and 81 non-MSI-H) were collected from patients undergoing colectomy for either CRC or hyperplastic polyposis. Twenty five of 57 serrated lesions were derived from four patients with hyperplastic polyposis. HP were further subdivided according to recently documented morphological criteria into 27 classical HP and 16 variant lesions described as "sessile serrated adenoma" (SSA). All tumours were screened for BRAF activating mutations. RESULTS: The BRAF mutation was more frequent in SSA (75%) and MP (89%) than in classical HP (19%), SA (20%), and AD (0%) (p<0.0001), and also in sporadic MSI-H cancers (76%) compared with HNPCC (0%) and sporadic non-MSI-H cancers (9%) (p<0.0001). The BRAF mutation was identified more often in CIMP-high serrated polyps (72%) and CIMP-high CRC (77%) than in CIMP-low (30%) and CIMP-negative (13%) polyps (p = 0.002) as well as CIMP-low (18%) and CIMP-negative (0%) CRC (p<0.0001). CONCLUSIONS: The BRAF mutation was frequently seen in SSA and in sporadic MSI-H CRC, both of which were associated with DNA methylation. Sporadic MSI-H cancers may originate in SSA and not adenomas, and BRAF mutation and DNA methylation are early events in this "serrated" pathway.     

Clinicopathologic findings of colorectal traditional and sessile serrated adenomas in Korea: a multicenter study

Background/Aims: Serrated polyps have emerged as important evidence supporting the serrated polyp-neoplasia pathway in colorectal carcinogenesis, an alternate to the classical adenoma-carcinoma sequence. However, there is confusion over the diagnostic criteria for serrated polyps including traditional serrated adenoma (TSA) and sessile serrated adenoma (SSA). In addition, clinical and pathologic characteristics of each are largely unknown and need further exploration. Methods: The 753 polyps that were previously diagnosed as serrated adenoma (SA) from 14 tertiary care university hospitals in Korea between 2003 and 2005 were evaluated for the clinicopathologic findings of TSA and SSA. Results: Among 753 cases, 420 (55.8%) were reclassified as TSA and 56 (7.4%) as SSA. Among the pathologic parameters, crypt branching, crypt dilatation, and horizontal crypts were more frequent in SSA than in TSA (p < 0.001). SSA was larger than TSA (12.6 +/- 7.3 vs. 9.8 +/- 6.9 mm, p = 0.005), was more likely to be flat type (p = 0.006), and was more frequently located in the proximal colorectum (p = 0.012). There were no significant differences in age, sex, and body mass index between TSA and SSA. Conclusions: Locationand endoscopic features of the polyps with abnormal crypt morphology in histologic findings could be helpful for the diagnosis and classification of SAs.     

High prevalence of sessile serrated adenomas with BRAF mutations: a prospective study of patients undergoing colonoscopy

BACKGROUND & AIMS: Sporadic colorectal cancers with a high degree of microsatellite instability are a clinically distinct subgroup with a high incidence of BRAF mutation and are widely considered to develop from serrated polyps. Previous studies of serrated polyps have been highly selected and largely retrospective. This prospective study examined the prevalence of sessile serrated adenomas and determined the incidence of BRAF and K-ras mutations in different types of polyps. METHODS: An unselected consecutive series of 190 patients underwent magnifying chromoendoscopy. Polyp location, size, and histologic classification were recorded. All polyps were screened for BRAF V600E and K-ras codon 12 and 13 mutations. RESULTS: Polyps were detected in 72% of patients. Most (60%) were adenomas (tubular adenomas, tubulovillous adenomas), followed by hyperplastic polyps (29%), sessile serrated adenomas (SSAs; 9%), traditional serrated adenomas (0.7%), and mixed polyps (1.7%). Adenomas were more prevalent in the proximal colon (73%), as were SSAs (75%), which tended to be large (64% >5 mm). The presence of at least one SSA was associated with increased polyp burden (5.0 vs 2.5; P < .0001) and female sex (P < .05). BRAF mutation was rare in adenomas (1/248 [0.4%]) but common in SSAs (78%), traditional serrated adenomas (66%), mixed polyps (57%), and microvesicular hyperplastic polyps (70%). K-ras mutations were significantly associated with goblet cell hyperplastic polyps and tubulovillous adenomas (P < .001). CONCLUSIONS: The prevalence of SSAs is approximately 9% in patients undergoing colonoscopy. They are associated with BRAF mutation, proximal location, female sex, and presence of multiple polyps. These findings emphasize the importance of identifying and removing these lesions for endoscopic prevention of colorectal cancer.     

Different apoptotic activity and p21<Superscript>WAF1/CIP1</Superscript>, but not p27<Superscript>Kip1</Superscript>, expression in serrated adenomas as compared with traditional adenomas and hyperplastic polyps of the colorectum

PURPOSE: Serrated adenomas (SAs), which include a wide spectrum of lesions, can be broadly divided into two subtypes: type I, closely mimicking hyperplastic polyps (HPs), and type II, unequivocal adenomatous tumor. Our preliminary findings showed clinicopathologic differences between them. The present study was conducted to investigate apoptotic activity and expression of the cell cycle regulator proteins p21(WAF1/CIP1) and p27(Kip1) in type I and II SAs, as compared with traditional adenomas (TAs) and HPs. METHODS: Apoptotic activity was estimated in hematoxylin-eosin stained specimens, and p21(WAF1/CIP1) or p27(Kip1) immunoreactivity was determined in 62 SAs (19 type I and 43 type II), 50 TAs and 19 HPs. The numbers (percentages) of apoptotic or immunoreactive cells were counted per 1,000 epithelial cells in equally separated crypt zones (upper, middle, and lower thirds). RESULTS: The apoptotic activity in the middle, but not the upper or lower crypt zone was higher in type II SAs (median 0.2%, interquartile range 0.1-0.5%) than in HPs (0.1%, 0.1-0.2%, P<0.01), whereas it was lower in type I SAs (0.2%, 0.1-0.3%) than in TAs (0.5%, 0.2-0.6%, P<0.001). P21(WAF1/CIP1) expression in the lower crypt zone was higher in both type I and type II SAs (19.8%, 7.0-33.2% and 20.4%, 3.9-47.8%, P<0.0001) than in TAs (1.2%, 0.6-5.2%), and a similar tendency was also observed for the middle crypt zone. p27(Kip1) expression did not vary among the groups. CONCLUSIONS: The differences in apoptotic activity and p21(WAF1/CIP1) expression between SAs and TAs or HPs indicate that SA should be considered as a distinct subtype of colorectal neoplasm. The two subtypes of SA do not differ in these parameters despite specific clinicopathological features.