Utility of cytokeratin 20 and Ki-67 as markers of urothelial dysplasia

Reactive urothelial atypia (RUA) can be difficult to differentiate from dysplastic urothelium. The goal was to evaluate the efficacy of cytokeratin 20 (CK20), Ki-67 and E-cadherin (E-Cad) in this regard. Fifty carcinoma in situ (CIS) cases, 50 non-neoplastic urothelia (25 normal, 25 reactive urothelial atypia (RUA)) and 17 atypia of unknown significance (AUS) cases were evaluated. All cases were stained with monoclonal antibodies against Ki-67, CK20 and E-Cad. All (100%) normal urothelia showed normal staining patterns. In the CIS group, 86%, 82% and 20% of cases showed abnormal expression with CK20, Ki-67 and E-Cad, respectively. Both Ki-67 and CK20 were positive in 68% of cases. In the RUA group, 96%, 72% and 100% of cases showed normal expression patterns with CK20, Ki-67 and E-Cad, respectively. Of 28% RUA cases with increased Ki-67, none demonstrated abnormal CK20 or E-Cad expression. In the AUS group, 47% demonstrated abnormal CK20 and increased Ki-67 expression, suggestive of urothelial dysplasia/CIS, 29% were negative with both, suggestive of RUA, and the remaining 24% cases could not be resolved. In summary, abnormal CK20 is a useful adjunct to morphology for confirming dysplasia. Ki-67 by itself is a less reliable marker of dysplasia. E-Cad is not a useful marker in this setting.     

Cellular differentiation status of epithelial polyps of the colorectum: the gastric foveolar cell-type in hyperplastic polyps

AIMS: The 'metaplastic' polyp of the colorectum, a synonym for the hyperplastic polyp, was named based only on features of the crypt epithelium. It is considered non-neoplastic, but the precise cellular differentiation status remains to be proven. METHODS AND RESULTS: Forty-eight hyperplastic polyps, 12 serrated adenomas, 45 tubular adenomas and five juvenile polyps were studied for their phenotypic expression using gastric (foveolar or pyloric gland cell), small intestinal (goblet cell), and colonic (goblet cell) cellular markers by immunohistochemical and mucin histochemical techniques. Gastric foveolar cell-type differentiation was significantly expressed in hyperplastic polyps, while colonic differentiation was also consistently preserved. Neither gastric pyloric-type nor small intestinal differentiation was observed. The same cell differentiation status as hyperplastic polyps was observed in serrated adenomas but not in tubular adenomas or juvenile polyps. CONCLUSIONS: A large proportion of hyperplastic polyps are composed of hybrid epithelium, with bidirectional differentiation to both gastric foveolar and colonic epithelial cells in the same crypt. Therefore hyperplastic polyps might be interpreted as the outcome of abnormal cell differentiation of stem cells. The same phenotypic expression suggests that hyperplastic polyps and serrated adenomas share the same cell lineage.     

甲状腺乳头状癌RET、CK19、TG、Ki-67的表达

目的 研究甲状腺乳头状癌RET、CK19、TG、Ki-67蛋白表达特点及其临床意义。方法 应用免疫组织化学SP法检测RET、CK19、TG、Ki-67蛋白在30例甲状腺乳头状癌、10例结节性甲状腺肿和18例癌旁正常甲状腺中的表达。结果 RET、CK19在乳头状癌的阳性率（66．7％、83．3％）明显高于结节性甲状腺肿和正常甲状腺阳性率（7．1％、25．0％）,两者差异有显著性（P〈0．01）。乳头状癌组及良性病例组TG表达阳性率差异无显著性（P〉0．05）。96．7％的乳头状癌Ki-67阳性细胞数小于10％。结论 RET及CK19在甲状腺乳头状癌表达增加,具有一定的病理诊断价值。     

Metaplastic polyps and polyposis of the colorectum

Five hundred and fifty-four colorectal metaplastic polyps have been studied histologically. Whilst most lesions were small and sessile, 16.1% measured greater than 0.5 cm in diameter and 0.9% were greater than 1 cm. The larger polyps were frequently pedunculated and occasionally showed a tubulo-villous or villous pattern. A structural similarity between the larger metaplastic polyps and colorectal adenomas is illustrated and the importance of the distinction of metaplastic from dysplastic epithelium in the differentiation of these lesions is stressed. Other unusual features of metaplastic polyps are described. Evidence is given to suggest that males have a greater propensity to develop metaplastic polyps than females. A search for metaplastic-like areas in other colorectal polyps revealed that they are rare (0.6%) in adenomas, but relatively frequent (20.8%) in juvenile polyps. Finally, seven patients with multiple metaplastic polyps of the colorectum are described, in whom a diagnosis of adenomatous polyposis had been made at some stage in their management. Six of the seven patients were males and the mean age at presentation was 37.4 years. Larger metaplastic polyps were frequent in these cases. The necessity for histological confirmation in all cases of intestinal polyposis is stressed, and the possibility that 'metaplastic polyposis' is a pathological entity is discussed.     

胃癌组织中c-FLIP及Ki-67表达的研究

目的 研究胃癌组织中c-FLIP及Ki-67的表达情况,并依此探讨胃癌细胞的凋亡与增殖之间的关系.方法 应用免疫组织化学的方法研究c-FLIP及Ki-67在100例胃癌标本中及100例胃良性疾病标本中的表达情况.结果 在胃癌组织中c-FLIP(χ2=35.17,P<0.01)及KI有较高表达(u=13.52,P<0.01);不同分化程度的胃癌标本中,c-FLIP表达差别有统计学意义(χ2=14.83,P<0.01),而KI差别无统计学意义(u=1.00,P>0.05).结论 在胃癌的发生与发展中,细胞凋亡受抑制与细胞增殖过度之间存在相互协同作用.     

Morphological range of hyperplastic polyps and carcinomas arising in hyperplastic polyps of the stomach.

A morphological range of 67 hyperplastic polyps was studied. They included polyps removed endoscopically and polyps found incidentally in resected stomachs with gastric ulcers and cancer. The hyperplastic polyps were essentially composed of cystic foveolae and pyloric type glands, lined by cells identical to those of the normal gastric mucosa. Thirty one polyps contained other cytological elements. In 18, intestinal metaplasia was seen; the tubules were mostly composed of columnar and goblet cells and lacked Paneth cells. In 11 polyps, nine cases of gastric dysplasia and two cases of intestinal dysplasia, dysplastic changes were found. The former consisted of a proliferation of irregularly shaped pits with pleomorphic cuboidal/columnar cells with relatively basophilic cytoplasm. They contained mucigen granules of a gastric type. The latter consisted of atypical pits composed of closely packed, tall columnar and small goblet cells, both resembling adenomatous cells of the colon. In three polyps carcinomas were seen, one of which was an intestinal type adenocarcinoma. In the other two, the cancer cells closely resembled the normal foveolar cells, containing gastric type mucigen granules. They were gastric type adenocarcinomas.     

Smoking, folate and methylenetetrahydrofolate reductase status as interactive determinants of adenomatous and hyperplastic polyps of colorectum.

Most studies demonstrate increased risk of colorectal cancer (CRC) and adenomas in folate-deficient subjects or that high folate intake may afford some protection. Smoking increases such risk in some but not all studies. We investigated whether smoking, folate status and methylenetetrahydrofolate reductase (MTHFR) genotype predict the risk of adenomatous and hyperplastic polyps of colorectum. By colonoscopy, the type, number, size and extent of dysplasia of colorectal polyps were assessed in 443 subjects aged 63-72 years. We also determined RBC folate and the C667T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. Smoking, folate status and the C677T MTHFR polymorphism were strong, interactive determinants of high-risk adenomas (HRAs, defined as adenomas > or =10 mm in diameter, adenomas with villous components or with severe dysplasia). The risk was particularly high in smokers with low folate and the CT/TT genotype (risk category T) and in smokers with high folate and the CC genotype (risk category C). With non-smokers with low folate and the CC genotype as reference, the odds ratios (OR, 95% CI) were 8.7 (2.5-29.7) in category T and 9.9 (2.6-38.4) in category C. Notably, this risk pattern was also observed for hyperplastic polyps. In conclusion, in smokers, high folate status may confer increased or decreased risk for HRAs, depending on the MTHFR genotype. These data demonstrate the strong gene-nutrition interaction involving the C677T MTHFR polymorphism.     

前列腺疾病中TK1和Ki-67的表达

目的通过对前列腺癌、前列腺上皮内瘤变、前列腺良性增生及其正常前列腺组织中胸苷激酶1（TK1）和细胞增殖蛋白（MIB-1）标记Ki-67的表达，探讨其对前列腺癌的治疗、预后所起的作用。方法采用免疫组化ABC法检测前列腺癌（PCa）42例，前列腺上皮内瘤变（PIN）35例，良性前列腺增生（BPH）25例和正常前列腺（NP）组织10例中TK1及Ki-67的表达。结果良性前列腺增生及正常前列腺组织中几乎检测不到增殖细胞，在前列腺上皮内瘤中增殖细胞所占的百分比大约为16％～17％，在前列腺癌组织中TK1阳性表达率57．1％，高于Ki-67阳性表达率（47．6％，P〈0．05）。结论TK1不仅同Ki-67一样，可作细胞增殖的指标，还因其参与DNA合成及细胞间“旁观者效应”等原因，从而给临床提供治疗及预后方面有价值的参考。     

Expression of cytokeratin 20 in mucinous bronchioloalveolar carcinoma

Mucinous bronchioloalveolar carcinomas (BACs) can closely mimic metastatic adenocarcinoma to the lung both clinically and morphologically. Several studies have demonstrated that the differential expression of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) is a valuable diagnostic tool in differentiating primary pulmonary adenocarcinomas (PPAs) (usually CK7 positive/CK20 negative) from metastatic colonic adenocarcinoma (usually CK7 negative/CK20 positive). The present study is designed to correlate the histologic subtypes of PPA with expression of 7 and 20. A total of 113 cases of bonafide PPA were selected and classified according to the 1999 World Health Organization criteria as adenocarcinoma, NOS (n = 80), nonmucinous BAC (n = 14), and mucinous BAC (n = 19). Representive sections of all the tumors were immunohistochemically analyzed for CK7 and CK20 expression. To evaluate the diagnostic utility of CK7 and CK20 expression, 6 cases of colonic adenocarcinoma metastatic to the lung were tested with the same antibodies and compared with mucinous BAC. Results were expressed in a semiquantitative fashion based on the percentage of positive tumor cells: <10%, focal; 10% to 25%, 1+; 26% to 75%, 2+; > or =76%, 3+. All 113 PPAs exhibited strong, diffuse CK7 expression. With respect to CK20 expression, 17 of the 19 cases (89.4%) of mucinous BAC showed moderate to strong expression of this protein, whereas only 10 cases of conventional adenocarcinomas and 4 cases of nonmucinous BAC exhibited expression. All 6 examples of metastatic colonic adenocarcinomas were negative for CK7 and strongly positive for CK20. In summary, mucinous BAC is distinct from other PPAs by virtue of its CK20 expression. Although the CK7/CK20 immunoprofile is a valuable diagnostic marker for differentiating primary lung adenocarcinoma from metastatic colonic adenocarcinoma, caution should be exercised when dealing with mucinous BAC.     

A useful panel in proliferative urothelial lesions: an analysis of cytokeratin 20, p53, CD44 and Ki-67 antigens

Urothelium can show several pseudoneoplastic lesions. Mimic lesions diagnosis is therapeutically and prognostically critical but it is often difficult on the basis of morphology alone in bladder biopsy specimen. We studied in a retrospective way an immunohistochemical panel that helps in this differential diagnosis. The panel includes antibodies against cytokeratin 20 (CK20), CD44, Ki67 (MIB-1) e p53 and we applied it to 31 cases of non-neoplastic urothelium (26 urothelial biopsies with reactive atypia and 5 normal urothelium) and 50 cases of urothelial neoplasia where we analized the distribution of the markers over the urothelium. We obtained two different "standard" results, for neoplastic and non-neoplastic urothelium. We were able to prove that this panel is useful, non expensive tool in the differential diagnosis of urothelial proliferative lesions.     

Ki-67及ezrin在子宫内膜腺癌中的表达及意义

目的　探讨Ki 6 7及ezrin在子宫内膜癌中的表达及意义。方法　应用免疫组化方法检测Ki 6 7和ezrin在子宫内膜腺癌、非典型增生、子宫内膜增殖症及正常内膜中的表达 ;应用RT PCR技术对Ki 6 7 和ezrin mRNA在子宫内膜癌及正常内膜中的表达进行半定量分析。结果　Ki 6 7指数在子宫内膜癌、非典型增生及子宫内膜增殖症分别为 39.9± 6 .4、1 8.9± 1 4 .7、1 8.6± 1 5 .3,明显高于正常子宫内膜的 1 .1± 1 .6 7(P <0 .0 5 )。正常及子宫内膜增殖症的ezrin表达几乎全集中于细胞膜上 ,而子宫内膜癌及非典型增生的ezrin表达则为细胞浆内的弥漫性染色。在子宫内膜癌组织中 ,Ki 6 7mRNA表达为 0 .6 0 75± 0 .0 887,高于正常内膜组织的 0 .35 32± 0 .1 2 6 7。结论　Ki 6 7抗原过量表达与子宫内膜癌的发生及恶性程度密切相关 ;ezrin的着色部位对子宫内膜病变的性质有标识作用     

子宫内膜样腺癌中Stathmin和Ki-67的表达及意义

目的:研究Stathmin和Ki-67在子宫内膜样腺癌和正常子宫内膜中的表达差异,探讨Stathmin和Ki-67在子宫内膜样腺癌发生发展过程中的意义.方法:采用免疫组织化学法检测99例子宫内膜样腺癌及67例正常子宫内膜中Stathmin和Ki-67的表达情况.结果:子宫内膜样腺癌中Stathmin和Ki-67表达率分别为75.8%,70.7%,显著高于正常子宫内膜中的9.0%,4.5%,差异有统计学意义(P<0.05);Stathmin和Ki-67表达与子宫内膜样腺癌组织学分级相关(P<0.05),与患者年龄、临床分期、浸润深度、淋巴结转移及脉管侵犯无关(P>0.05);Stathmin表达和Ki-67表达呈正相关(r=0.672,P<0.05).结论:子宫内膜样腺癌中Stathmin和Ki-67高表达可能共同参与子宫内膜样腺癌发生和分化;Stathmin和Ki-67表达呈正相关,提示Stathmin高表达可能与子宫内膜样腺癌高增殖性相关.     

尖锐湿疣角质形成细胞凋亡及Ki-67的表达

目的：研究尖锐湿疣（ＣＡ）角质形成细胞的凋亡及Ｋｉ－６７的表达及其相关性。方法：对４８例ＣＡ采用ＴＵＮＥＬ技术原位检测其细胞的凋亡,用免疫组化方法,观察Ｋｉ－６７阳性的表达。结果：表皮中见到典型的凋亡细胞,表皮各层中有较多Ｋｉ－６７阳性细胞。病理严重度与凋亡指数无显著差异性（Ｐ〉０．０５）;与Ｋｉ－６７阳性细胞指数比较则有显著差异性（Ｐ〈０．００５）。凋亡细胞与Ｋｉ－６７阳性细胞之间呈负相关（ｒ＝     

细胞角蛋白7和20在卵巢转移癌中的表达

目的 观察卵巢转移癌的临床资料、病理形态和免疫组织化学改变,为鉴别卵巢转移癌与原发癌提供依据。方法 对27例卵巢转移癌（其中胃癌12例,结肠癌11例,其他4例）进行了临床和病理形态观察,同时采用免疫组织化学（SP法）对其分别进行细胞角蛋白[CK（AE1/AE3）]、细胞角蛋白7（CK7）、细胞角蛋白20（CK20）、癌胚抗原、波形蛋白、nm23抗原检测。结果 卵巢转移性胃癌12例中11例为双侧实性,卵巢转移性结肠癌11例中7例为单侧囊实性,组织学检查胃癌卵巢转移12例全部以印戒细胞癌或低分化腺癌散在分布为特征,而结肠癌卵巢转移则11例中8例与子宫内膜样癌相似,CK20阳性染色使卵巢转移性胃癌7例及结肠癌8例得到明确诊断,在转移性结肠癌中CK20有稳定的表达,卵巢转移性胃肠道癌中CK7多数阴性,癌胚抗原、波形蛋白、nm23的联合使用使转移性胃癌11例,结肠癌10例得到明确诊断,结论 CK7和CK20在鉴别来自胃肠道的卵巢转移癌中具有重要意义。当几种抗体联合使用时意义更大。     

My approach to serrated polyps of the colorectum

Hyperplastic polyps of the colorectum are heterogeneous lesions, a subset of which is now regarded as the precursor of colorectal cancer with DNA microsatellite instability. Some authors have distinguished this subset from classic hyperplastic polyps and have introduced the term "sessile serrated adenoma". These lesions frequently show BRAF mutation and DNA methylation. This personal perspective reviews recent insights into serrated polyps and highlights the importance of inhibition of apoptosis as a unifying mechanism. It is estimated that around 25 hyperplastic polyps of the proximal colon exist for every colorectal cancer with DNA microsatellite instability. Further research is required to identify additional risk factors for hyperplastic polyps other than anatomical location. These may be demographic, clinical, morphological, or molecular. It is not recommended that the term sessile serrated adenoma be used in routine reporting, but it is desirable that potentially aggressive hyperplastic polyps should be identified for the purposes of both clinical practice and research.