结直肠锯齿状病变104例形态学及细胞增殖活性的观察

目的 探讨结直肠锯齿状病变增生性息肉(HP)、广基锯齿状腺瘤(SSA)、传统锯齿状腺瘤(TSA)的临床特征,组织病理学诊断,鉴别诊断及细胞增殖状况.方法 复习北京军区总医院2002年11月至2007年12月2628例病理诊断为结直肠息肉/腺瘤的病理切片,从中收集104例结直肠锯齿状病变,综合文献标准进行分类,观察各类型病变临床病理学特征,以及细胞增殖指数Ki-67的表达特点.结果 104例锯齿状病变中包括HP 60例,TSA 20例,SSA 11例,混合性锯齿状息肉/腺瘤7例,混合件锯齿状息肉/腺瘤+普通腺瘤6例.对各型组织学特征进行总结归纳.免疫组织化学显示正常结肠黏膜Ki-67阳性细胞位于基底(隐窝下1/3),呈间隔分布;51例HP中阴性或阳性细胞数最<25%的40例(78%),大多数阳性位于隐窝下1/3(基底);15例TSA中11例阳性细胞数量在25%～50%或>50%,其中大多数位于隐窝中1/3,少数(2例)隐窝弥漫分布;SSA的数量与分布和TSA相似;相比之下低级别管状腺瘤26例中24例(92%)阳性数量>50%,18例(69%)分布于隐窝表面,6例(23%)弥漫分布;高分化管状腺癌10例全部呈弥漫分布,7例Ki-67阳性指数在70%左右.阳性细胞多少与分布部位差异有统计学意义,阳性细胞)χ2=34.601,P=0.000,阳性分布χ2=63.077,P=0.000.结论 HP、SSA、TSA组织学鉴别诊断的主要难点是在HP与SSA两者之间,SSA锯齿状隐窝基底扩张结构特征是诊断的关键,比细胞学改变更重要.TSA与SSA的主要形态鉴别在于TSA锯齿状腺体有明显异型增生(普通腺瘤样增生)以及几乎所有TSA异型增生的腺体都不与黏膜肌相邻(ECF现象).细胞增殖指数Ki-67数量及分布的表达可为HP、SSA及TSA鉴别诊断提供一定帮助.锯齿状腺瘤中TSA和SSA的Ki-67表达指数都比普通腺瘤要低.     

结直肠锯齿状病变及癌变组织中PI3Kp110α、PI3Kp110β的表达及意义

目的探讨PI3Kp110α、PI3Kp110β在结直肠锯齿状病变及其癌变组织中的表达及意义。方法采用免疫组化和Western blot法检测PI3Kp110α、PI3Kp110β在结直肠正常黏膜、管状腺瘤、锯齿状病变及来自管状腺瘤和锯齿状腺瘤癌变组织中的表达,并分析二者表达与临床病理特征的关系。结果 PI3Kp110α、PI3Kp110β在腺癌组、不同级别锯齿状腺瘤组及高级别管状腺瘤组中均呈高表达,且明显高于增生性息肉、低级别管状腺瘤及正常黏膜组织(P0.05),但组间相比差异无显著性(P0.05)。锯齿状腺瘤中PI3Kp110α、PI3Kp110β的表达与肿瘤大小有关、肿瘤数目有关(P0.05)。腺癌组中PI3Kp110α、PI3Kp110β表达与肿瘤分化程度及淋巴结转移有关(P0.05)。结论 PI3Kp110α与PI3Kp110β在锯齿状腺瘤及腺瘤癌变中呈高表达,二者可能是促进腺瘤恶变的危险因素,联合检测PI3Kp110α和PI3Kp110β在结直肠锯齿状腺瘤中的表达有助于判断其恶性潜能。     

结直肠锯齿状病变8例临床病理分析

目的：分析结直肠锯齿状病变的病理分类及鉴定诊断要点。方法运用形态学方法回顾性分析72例结直肠腺瘤性息肉及83例结直肠增生性息肉的临床资料,综合文献标准对其进行分类。结果72例结直肠腺瘤性息肉及83例结直肠增生性息肉中8例结直肠病变腺体有锯齿状结构,其中4例为锯齿状形态的增生性息肉( hyperplastic polyps, HP),2例为传统锯齿状腺瘤( traditional serrated adenoma, TSA),1例为广基锯齿状腺瘤( sessile serrated adenoma, SSA),1例为混合性息肉(mixed polyposis, MP)。每一种病变在形态上均有与同其他各型组织学相异的特征。结论利用形态学方法能够对各类结直肠锯齿状病变进行诊断和鉴别,提升对结直肠锯齿状病变的认识,提升临床诊断的正确率。     

结直肠异常隐窝灶中BAI1、VEGF蛋白表达及意义

目的观察BAI1、VEGF在结肠异型增生性异常隐窝灶(aberrant crypt foci,ACF)、管状腺瘤及腺瘤癌变中的表达。方法联合放大内镜窄带成像(narrow-band imaging,NBI)技术观察ACF,采用免疫组化法检测40例异型增生性ACF、40例结肠管状腺瘤伴异型增生、35例管状腺瘤癌变及32例结直肠正常黏膜标本中BAI1和VEGF的表达。结果 BAI1蛋白在结直肠正常黏膜、异型增生性ACF、结肠管状腺瘤伴异型增生及管状腺瘤癌变组中的阳性率逐步降低,分别为93.8%、72.5%、45%、11.4%,且异型增生性ACF组阳性率明显低于结直肠正常黏膜组(P0.05),结肠管状腺瘤伴异型增生组阳性率明显低于异型增生性ACF组(P0.05),管状腺瘤癌变组阳性率明显低于管状腺瘤伴异型增生组(P0.05);VEGF蛋白在结直肠正常黏膜、异型增生性ACF、管状腺瘤伴异型增生及管状腺瘤癌变组中的阳性率逐步升高,分别为9.4%、52.5%、62.5%、94.3%,且异型增生性ACF组阳性率明显高于结直肠正常黏膜组(P0.05),管状腺瘤癌变组阳性率明显高于异型增生性ACF组及管状腺瘤伴异型增生组(P0.05);在异型增生性ACF、管状腺瘤及管状腺瘤癌变过程中BAI1和VEGF表达呈负相关(rs=-0.656,P0.05)。结论 BAI1低表达与VEGF高表达可能在结直肠癌前病变中起一定作用,可能为结直肠肿瘤的早期诊治提供新的作用靶点。     

结直肠癌前病变与结直肠腺癌免疫表型及基因突变分析

目的 分析结直肠癌前病变与结直肠腺癌免疫表型及基因突变特征,比较两种结直肠癌前病变癌变机制的差异.方法 收集2006年1月至2012年6月间诊断的53例结直肠锯齿状病变,包括30例增生性息肉、20例广基锯齿状腺瘤(SSA)及3例混合性息肉;同时选取45例传统腺瘤、50例结直肠腺癌.采用免疫组织化学EnVision法检测30例增生性息肉、20例SSA、3例混合性息肉以及45例传统腺瘤DNA错配修复(MMR)蛋白MLH1、MSH2、MSH6及甲基转移酶MGMT蛋白的表达情况;采用Sanger直接测序法检测10例SSA、10例传统腺瘤、l例混合性息肉及50例结直肠腺癌中KRAS、BRAF及PIK3CA基因的突变情况.结果 (1)MLH1蛋白在增生性息肉中仅3例阴性(10％),在SSA、传统腺瘤中均呈阳性.MSH2、MSH6及MGMT蛋白在增生性息肉及SSA中的阴性率明显高于传统腺瘤,差异均具有统计学意义(P＜O.01).(2)结直肠SSA和传统腺瘤中KRAS基因突变比例为5/10,5/10;1例混合性息肉存在KRAS基因突变.(3)结直肠腺癌中,KRAS、BRAF及PIK3CA基因突变率分别为48％ (24/50)、6％ (3/50)及4％(2/50).结论 结直肠锯齿状病变与传统腺瘤在免疫表型及基因突变等方面存在着一定的差异,MMR与MGMT在“锯齿状肿瘤”癌变通路中起着重要的作用.KRAS基因突变是结直肠腺癌癌变过程中发生较早的重要遗传学改变.     

Wnt信号通路成员蛋白NKD1、β-catenin和Cyclin D1在结直肠腺癌中的表达及意义

目的观察NKD1、β-catenin和Cyclin D1蛋白在结直肠正常黏膜、腺瘤和腺癌组织中的表达,探讨NKD1、β-catenin和Cyclin D1在结直肠正常黏膜-腺瘤-腺癌这一癌变过程中的表达变化及临床意义。方法应用免疫组化SP法检测38例结直肠正常黏膜、70例腺瘤、128例腺癌组织中NKD1、β-catenin和Cyclin D1蛋白的表达。结果 NKD1在结直肠正常黏膜、腺瘤、腺癌组织中的阳性率依次降低(P0.05),其在轻度异型增生腺瘤组织中的阳性率高于重度异型增生腺瘤组织(P0.05);β-catenin异位表达率与Cyclin D1阳性率在结直肠正常黏膜、腺瘤、腺癌组织中均依次升高(P0.01),且Cyclin D1在重度异型增生腺瘤组织中的阳性率高于中度及轻度异型增生腺瘤(P0.05)。NKD1、β-catenin、Cyclin D1在结直肠腺癌组织中的表达均与癌分化程度、Duke分期、淋巴结转移有关(P0.05)。在结直肠腺癌组织中NKD1的阳性率和β-catenin异位表达率呈负相关(r_s=-0.645,P0.01)。在结直肠腺癌组织中β-catenin异位表达率和Cyclin D1阳性率呈正相关(r_s=0.618,P0.01)。结论 NKD1、β-catenin、Cyclin D1三者可能参与结直肠肿瘤的发生、发展,有望成为评价结直肠腺癌恶性程度及预后的指标。     

结直肠腺瘤伴黏膜下层假性浸润的病理形态学特征观察

目的探讨结直肠腺瘤伴黏膜下层假性浸润的病理形态学特征,并总结相应的假性浸润模式。方法收集2016—2019年间解放军联勤保障部队第九八九医院病理科4例和首都医科大学附属北京朝阳医院病理科5例结直肠腺瘤伴黏膜下层假性浸润的病例,共计9例,观察其组织形态学特征和免疫表型,并结合文献进行分析。结果结肠有蒂腺瘤8例,黏膜下层可见肿瘤性腺体,类似浸润性腺癌。黏膜下层腺体结构和细胞形态与黏膜内肿瘤相同,局部黏膜下层肿瘤与黏膜内肿瘤有连续性。黏膜下层肿瘤呈推挤式的分叶状或巢团状,腺体轮廓平滑钝圆,腺体周围少量间质组织类似于黏膜固有层间质,部分病例腺体外围黏膜肌错综增生,并常见黏膜肌包绕腺体。有些病例黏膜下层腺体扩张、间质内黏液结节形成及含铁血黄素沉积。1例为发生在直肠的广基隆起型腺瘤伴局部高级别异型增生累及集合淋巴小结形成淋巴腺复合体,并陷入黏膜下层,类似浸润性腺癌周围被淋巴组织包绕。淋巴腺复合体内的肿瘤腺体和黏膜内病变相延续,并且组织学形态相同,肿瘤前缘可见腺体轮廓呈推挤式类圆形,以及不连续的黏膜肌,无典型浸润性腺癌所有伴有的纤维间质反应、肿瘤出芽、腺体锐角分支及脉管浸润等形态特征。结论结直肠腺瘤伴黏膜下层假性浸润可总结为两种独特的形态学模式,模式一为分叶状,缺少淋巴组织反应;模式二为淋巴腺复合体样。两种模式的主要特征为黏膜下层肿瘤和黏膜内肿瘤形态相同,并有连续性,推挤式的腺体周围伴固有膜间质和黏膜肌包绕,并且无典型浸润性腺癌的形态特征。     

以阑尾炎起病的阑尾上皮性肿瘤15例临床病理分析

目的:探讨以阑尾炎起病的阑尾上皮性肿瘤的临床病理学特征.方法:对15例以阑尾炎起病的阑尾上皮性肿瘤的临床病理资料进行回顾性分析.结果:15例以阑尾炎起病的阑尾上皮性肿瘤中,6例为低级别阑尾黏液性肿瘤(low-grade appendiceal mucinous neoplasm,LAMN),其余9例为前驱病变,包括8例锯齿状病变及1例绒毛状-管状腺瘤,其中锯齿状病变为6例无蒂锯齿状腺瘤/息肉(sessile serrated adenoma/polyp,SSA/P)及2例传统型锯齿状腺瘤(traditional serrated adenoma,TSA).14例以"急性阑尾炎"起病,1例以"慢性阑尾炎"起病.SSA/P镜下见锯齿状结构、隐窝扩张呈L或倒T形;TSA见显著的锯齿状轮廓和异位隐窝,具有细胞异型性;锯齿状病变的黏膜肌层完整.LAMN内衬轻度异性的黏液性上皮,管壁纤维化或破裂,管壁内及浆膜见无细胞性黏液池.9例获得随访包括5例前驱病变及4例LAMN,随访时间1.0~81.5个月,患者均无病生存.结论:阑尾锯齿状病变及LAMN均可因急性阑尾炎起病,锯齿状病变大多数为镜下偶然发现.外科医生应提高对这些病变的认识,以避免医源性穿孔导致的腹膜假黏液瘤.病理医生应将该类阑尾病变标本全部取材以便于鉴别诊断,报告阑尾切缘情况.     

Expression of MMP-7 and its significance in the malignant transformation of colorectal adenoma

目的 检测MMP-7在大肠管状腺瘤和大肠管状腺瘤癌变组织中的表达,探讨其在癌变过程中的作用,为临床诊断、治疗及预后判断提供新的理论依据.方法 采用免疫组化EliVision两步法研究40例大肠黏膜、82例散发性大肠管状腺瘤、76例大肠管状腺瘤癌变组织中MMP-7的表达.结果 大肠黏膜、散发性大肠管状腺瘤伴上皮不同程度异型增生和大肠管状腺瘤癌变组织中MMP-7阳性率分别为2.5%、32.9%、86.8%.随着病变程度的加深表达逐渐增高,差异具有统计学意义(P<0.05).大肠管状腺瘤伴上皮不同程度异型增生组中MMP-7的阳性率分别为15.4%(轻、中度)、63.3%(重度),阳性率逐渐增高(P<0.05).MMP-7在腺瘤癌变中的表达与年龄、肿瘤的分化程度、浸润深度、淋巴结转移及Dukes分期有关(P<0.05),与性别无关(P>0.05).结论 大肠管状腺瘤癌变过程中MMP-7的阳性率逐渐升高,MMP-7可能参与大肠管状腺瘤癌变的发生.     

大肠管状腺瘤癌变过程中MMP-7的表达及意义

目的检测MMP-7在大肠管状腺瘤和大肠管状腺瘤癌变组织中的表达,探讨其在癌变过程中的作用,为临床诊断、治疗及预后判断提供新的理论依据。方法采用免疫组化EliVision两步法研究40例大肠黏膜、82例散发性大肠管状腺瘤、76例大肠管状腺瘤癌变组织中MMP-7的表达。结果大肠黏膜、散发性大肠管状腺瘤伴上皮不同程度异型增生和大肠管状腺瘤癌变组织中MMP-7阳性率分别为2.5%、32.9%、86.8%。随着病变程度的加深表达逐渐增高,差异具有统计学意义(P<0.05)。大肠管状腺瘤伴上皮不同程度异型增生组中MMP-7的阳性率分别为15.4%(轻、中度)、63.3%(重度),阳性率逐渐增高(P<0.05)。MMP-7在腺瘤癌变中的表达与年龄、肿瘤的分化程度、浸润深度、淋巴结转移及Dukes分期有关(P<0.05),与性别无关(P>0.05)。结论大肠管状腺瘤癌变过程中MMP-7的阳性率逐渐升高,MMP-7可能参与大肠管状腺瘤癌变的发生。     

Serrated adenomas of the appendix

AIMS: A review of the literature indicated that only one case of serrated adenoma of the appendix has been recorded. The aim was to explore the possible occurrence of serrated adenomas of the appendix at the department of pathology, Karolinska Institute and University Hospital, Stockholm, Sweden. METHODS: Between January 1993 and December 2003, 38 non-carcinoid, non-neoplastic, or neoplastic polyps or tumours of the appendix were surgically removed at this hospital. All filed histological sections (haematoxylin and eosin stained) were reviewed. RESULTS: Of the 38 lesions, four were hyperplastic polyps, 10 serrated adenomas, six villous adenomas, and the remaining eight mucinous adenocarcinomas without a remnant adenoma. Serrated adenomas accounted for six of the 11 adenomas without invasion, and four of the 15 adenomas with invasive carcinoma. At the time of surgical resection, four of the 10 serrated adenomas had evolved into invasive carcinomas, in addition to 11 of the 16 villous adenomas. CONCLUSIONS: Serrated and villous adenomas of the appendix appear to be highly aggressive lesions, more aggressive than similar adenomas in the colon and rectum. Of the seven cases with a hyperplastic polyp, one concurred with a serrated adenoma, two with a serrated adenoma having an invasive carcinoma, and one with invasive carcinoma without a remnant adenomatous structure. At present, there is an increased awareness that some hyperplastic polyps of the colon and rectum may evolve into serrated adenomas. Whether this pathway is also valid for the appendix vermiformis should be investigated in a larger number of cases.     

Serrated neoplasia of the stomach: a new entity

AIM: Despite the fact that gastric carcinoma continues to be one of the most common cancers world wide, only dysplasia in flat mucosa and adenomas have been shown to evolve into invasive carcinoma. The aim of this paper is to report a novel histological phenotype of gastric adenoma with early invasive growth. MATERIAL AND RESULTS: The patient presented with gastric complaints. A barium examination revealed an ulcerated tumour in the corpus, apparently infiltrating the gastric wall. The endoscopic examination showed a pediculated protruding tumour in the greater curvature. Punch biopsies were reported as invasive adenocarcinoma. Because of the poor condition of the patient, a partial gastrectomy was performed. The histological examination revealed elongated fronds with lateral crenated, saw tooth-like notches as a result of scalloped epithelial indentations. Areas with high grade dysplasia, with carcinoma in situ, and invasive carcinoma at the tip of the adenoma were demonstrated. The pedicle of the protruding neoplasia "emerged" from a non-protruding serrated adenoma. CONCLUSIONS: The protruding serrated neoplasia had apparently evolved from a non-protruding serrated gastric adenoma. This appears to be the first case of gastric serrated neoplasia in the literature.     

‘Serrated’ adenoma of the colorectum,with reference to its gastric differentiation and its malignant potential

Serrated adenoma of the colorectum was a newly proposed entity in 1990, characterized by epithelial neoplasia combining the architectural features of a hyperplastic (metaplastic) polyp with the cytological features of an adenoma. Its histogenesis and natural history still remain unclear. Forty-six serrated adenomas were obtained from 46 patients. The clinicopathological features were summarized. Paraffin-embedded blocks from 34 serrated adenomas were available for immunohistochemical studies using pS2, human gastric mucin, and p53 protein. Eighteen hyperplastic (metaplastic) polyps, 16 tubular adenomas, and 12 early-stage adenocarcinomas were randomly selected as control groups for immunohistochemical analysis. The patients' ages ranged from 32 to 86 (average 61·4) years. Males were more frequently affected than females. Serrated adenomas were predominantly present in the left-side of the colon and in the rectum (72 per cent). Their sizes ranged from 3 to 26mm (average 9·2mm). Six lesions (13 per cent) contained foci of high-grade dysplasia. These adenomas were significantly larger (12·7mm) than those containing no high-grade dysplasia (8·6mm). pS2 and human gastric mucin were expressed significantly more frequently in both hyperplastic (metaplastic) polyps and serrated adenomas than in tubular adenomas or adenocarcinomas. p53-positive cells were present in 18 of the 29 pure serrated adenomas (62 per cent) and in one of the five areas of low-grade dysplasia in serrated adenomas with high-grade dysplasia (20 per cent), most of which revealed a sporadic distribution. Only five of the 29 serated adenomas with no high-grade dysplasia (17 per cent) were regarded as demonstrating p53 overexpression. On the other hand, three of the five areas of high-grade dysplasia in serrated adenomas (60 per cent) revealed diffuse positivity (3+) for p53 protein. The serrated adenoma, which possibly shows gastric differentiation, is considered to be an independent histological entity among the various phenotypes of colorectal adenomas. Serrated adenoma would seem to be a precursor of carcinoma, its potential for malignant transformation being similar to that of the traditional tubular adenoma. It would also seem that p53 is involved in the serrated adenoma–carcinoma sequence. Copyright © 1999 John Wiley & Sons, Ltd.     

Immunohistochemical testing of conventional adenomas for loss of expression of mismatch repair proteins in Lynch syndrome mutation carriers: a case series from the Australasian site of the colon cancer family registry

Debate continues as to the usefulness of assessing adenomas for loss of mismatch repair protein expression to identify individuals with suspected Lynch syndrome. We tested 109 polyps from 69 proven mutation carriers (35 females and 34 males) belonging to 49 Lynch syndrome families. All polyps were tested by immunohistochemistry for four mismatch repair proteins MLH1, MSH2, MSH6 and PMS2. Detailed pathology review was performed by specialist gastrointestinal pathologists. The majority of polyps (86%) were conventional adenomas (n=94), with 65 tubular and 28 tubulovillous adenomas and a single villous adenoma. The remaining 15 lesions (14%) were serrated polyps. Overall, loss of mismatch repair expression was noted for 78/109 (72%) of polyps. Loss of mismatch repair expression was seen in 74 of 94 (79%) conventional adenomas, and 4 of 15 (27%) serrated polyps from mismatch repair gene mutation carriers. In all instances, loss of expression was consistent with the underlying germline mutation. Mismatch repair protein expression was lost in 27 of 29 adenomas with a villous component compared with 47 of 65 adenomas without this feature (93 vs 73%; P=0.028). A strong trend was observed for high-grade dysplasia. Mismatch repair deficiency was observed in 12 of 12 conventional adenomas with high-grade dysplasia compared with 60 of 79 with low-grade dysplasia (100 vs 76%; P=0.065). We were unable to demonstrate a significant association between conventional adenoma size or site and mismatch repair deficiency. All (4/4 or 100%) of the serrated polyps demonstrating mismatch repair deficiency were traditional serrated adenomas from a single family. Diagnostic testing of adenomas in suspected Lynch syndrome families is a useful alternative in cases where cancers are unavailable. The overwhelming majority of conventional adenomas from mutation carriers show loss of mismatch repair protein expression concordant with the underlying germline mutation.     

Histopathologische Diagnostik und Differenzialdiagnostik serratierter Polypen im Kolorektum

Until recently, two major types of colorectal epithelial polyps were distinguished: the adenoma and the hyperplastic polyp. While adenomas - because of their cytological atypia - were recognized as precursor lesions for colorectal carcinoma, hyperplastic polyps were perceived as harmless lesions without any potential for malignant progression, mainly because hyperplastic polyps lack cytological atypia. Meanwhile, it is evident that the lesions formerly classified as hyperplastic represent a heterogeneous group of polyps, some of which exhibit a significant risk of neoplastic progression. These lesions show characteristic epigenetic alterations not commonly seen in colorectal adenomas and progress to colorectal carcinoma via the so-called serrated pathway (CIMP pathway). This group of polyps is comprised not only of hyperplastic polyps, but also of sessile serrated adenomas (SSA), traditional serrated adenomas (TSA) and mixed polyps, showing serrated and "classical" adenomatous features. In a consensus conference of the working group of gastroenterological pathology of the German Society of Pathology, standardization of nomenclature and diagnostic criteria as well as recommendations for clinical management of these serrated polyps were formulated and are presented herein.     

Selective expression of gastric mucin MUC6 in colonic sessile serrated adenoma but not in hyperplastic polyp aids in morphological diagnosis of serrated polyps

Colonic sessile serrated adenoma, in contrast to hyperplastic polyp, is thought to be related to sporadic colorectal cancers with high microsatellite instability. However, the morphological distinction between these entities is difficult and subject to observer and sampling variation. Therefore, we elected to investigate the expression of gastric mucin MUC6 as a potential marker to separate the two in the hope of finding an objective and reproducible adjunct to morphological diagnosis. Endoscopic biopsies of colonic polyps with serrated architecture, but without cytological dysplasia were studied and categorized as sessile serrated adenoma or hyperplastic polyp, using previously published morphological criteria. Smaller groups of serrated polyps with cytological dysplasia (traditional serrated adenomas, filiform serrated adenomas and sessile serrated adenomas with cytological dysplasia) were also included. In total, 94 polyps were immunohistochemically stained with antibodies to MUC6 and to MLH-1. MUC6 was found to have 100% specificity in distinguishing sessile serrated adenoma (N=26; positive staining) from hyperplastic polyp (N=48; negative staining). Traditional serrated adenomas and filiform serrated adenomas were also negative for MUC6. Sessile serrated adenomas with cytological dysplasia were found to lose expression of MLH-1 in dysplastic areas, while retaining MUC6 expression. Neither anatomic location in the right or left colon nor polyp size appears to account for the differences in MUC6 expression.     

Inverse relationship between APC gene mutation in gastric adenomas and development of adenocarcinoma

Gastric cancer is common among the world, but genetic mechanisms of gastric carcinogenesis are not well understood. Gastric polypoid adenomas and flat dysplasias are regarded as precursor lesions. However, a detailed molecular study of these lesions has not been done to determine their role as precancerous lesions. We investigated mutations of the APC, beta-catenin, and K-ras genes, and microsatellite instability (MSI) status in 35 adenomas and 47 flat dysplasias without adenocarcinoma, 35 adenomas/dysplasias associated with adenocarcinomas, and 39 adenocarcinomas (20 diffuse type and 19 intestinal type). Somatic APC gene mutations were identified in 76% (59 of 78) of adenomas or flat dysplasias without associated adenocarcinoma, but in only 3% (1 of 30) of adenomas/dysplasias associated with adenocarcinoma, and in only 4% (3 of 69) of adenocarcinomas (P < 0.000001). No mutations of beta-catenin were found in adenocarcinomas, or adenomas/dysplasia without APC mutation. K-ras mutations were detected in 5% (4 of 82) of gastric adenomas/dysplasia without carcinoma, 3% (1 of 39) of adenocarcinomas without associated adenoma/dysplasia, and not in 32 adenocarcinomas with associated adenoma/dysplasia. High level of MSI (MSI-H) was more frequent in gastric adenoma/dysplasia associated with carcinoma (17%, 6 of 35) than in adenomas/dysplasia without carcinoma (3%, 2 of 75; P = 0.01). MSI-H was also more frequent in intestinal type adenocarcinoma (20%, 11 of 54) than in diffuse type (0%, 0 of 20; P = 0.03). APC gene mutations were present in six of nine (67%) of gastric adenomas/dysplasias with low level of MSI, but in none of the eight adenomas/dysplasia with MSI-H phenotype (P = 0.009). Our results indicate that somatic mutation of the APC gene plays an important role in the pathogenesis of gastric adenoma and dysplasia but has a limited role in neoplastic progression to adenocarcinoma. Gastric adenomas or dysplasias without APC mutations but with or without MSI may have a different biological behavior, and are precursors of intestinal-type of gastric adenocarcinomas.     

Histopathological and clinical evaluation of serrated adenomas of the colon and rectum.

We evaluated the diagnostic utility of the histological characteristics ascribed in the literature to serrated adenomas and developed a practical working model to allow their reliable identification. We also documented the frequency and location of serrated adenomas identified in an unselected series of individuals undergoing colonoscopic evaluation, as well as the clinical characteristics of those individuals. One hundred forty consecutive individuals (prospective polyp data set; 97 male, 43 female; age mean: 63.3 y; age range: 29-98 y) with 255 polyps were identified from 919 individuals undergoing colonoscopy. Further polyps previously removed from these individuals were added for the purpose of histological assessment (extended polyp data set, n = 380). All polyps were assessed by two independent examiners for eight selected architectural and cytological features of serrated adenomas. In the prospective polyp data set, 56 patients had 72 hyperplastic polyps, 7 had 9 serrated adenomas, 3 had 4 admixed polyps, and 98 had 170 conventional adenomas. There was no difference in the age, sex, or cancer association of the seven patients with serrated adenomas when compared with the case of other individuals with polyps. The prevalence of serrated adenomas was 9/919 (1%) in our population, with an average size of 5.8 mm. When assessing serrated adenomas histologically, the combination of nuclear dysplasia and serration of >/=20% of crypts provided the most accurate model for detection of these lesions (sensitivity 100%, specificity 97%). Other criteria provided supportive evidence but did not increase the diagnostic yield. The optimum model for the histological identification of the serrated adenoma includes the presence of a serrated architecture in >/=20% of crypts in association with surface epithelial dysplasia.