消化系癌中HCG表达及其意义

应用免疫细胞化学方法研究发现部分胃癌（５／４０）、肠癌（４／３２）、胰腺癌（５／４２）、胆囊癌（５／４０）和胆管癌（５／４２）含ＨＣＧ阳性细胞，ＨＣＧ阳性病例多表现为低或未分化癌、组织学分级Ⅲ级和易发生淋巴结或其他器官转移，提示ＨＣＧ阳性消化系癌恶性度高，预后不良。     

关于大肠癌内分泌细胞及其分泌激素意义的研究

目的了解内分泌型癌细胞（ＥＣ）及其分泌的部分激素在大肠癌中的表达,探讨其与大肠癌临床病理及预后的关系。方法应用免疫组化法对１１７例大肠癌中嗜铬蛋白Ａ（ＣＧＡ）及５种激素进行检测,其中１３例行电镜观察。结果４６例（３９．３％）含有ＣＧＡ阳性细胞（即ＥＣ）,其中３９例中２７例（６９．２％）检测到１种以上激素,ＥＣ阳性组淋巴结转移的发生率（６３．０％）高于阴性组（３９．４％）（Ｐ＜０．０５）,中低分化癌组ＥＣ（＋＋）的表达率（２５．５％）明显高于高分化癌组（６．９％）（Ｐ＜０．０５）,含ＥＣ的大肠癌生存期短,是评估预后的一个独立因子。激素５－ＨＴ、β－ＨＣＧ、ＧＬＵ、ＧＡＳＴ阳性的癌组织,分化及预后较差（Ｐ＞０．０５）。电镜观察与免疫组化检测大肠癌ＥＣ符合率达９２．３％。结论部分大肠癌中含分泌某些激素的ＥＣ,ＥＣ阳性的大肠癌组织分化差,易发生淋巴结转移,预后不良,可能与ＥＣ中某些激素产物促进肿瘤生长转移有关。     

HCG在肺癌中的表达及其意义

采用ＡＢＣ免疫组织化学法对１６５例肺癌进行ＨＣＧ检测。实验显示，ＨＣＧ的表达与肺癌的组织学类型和分化程度具有相关性，并发现浸润性强和有转移的肺癌，其中ＨＣＧ的阳性率显著高于浸润性弱和无转移者。研究提示，肺癌细胞的ＨＣＧ测定，对判断癌的组织学类型、分化程度和生物学行为均有一定的参考价值。     

胃癌细胞异位分泌人绒膜促性腺激素对微血管密度的影响

目的研究胃癌组织中人绒膜促性腺激素（ＨＣＧ）对微血管密度（ＭＶＤ）的影响。方法运用ＳＰ法,对４０例胃癌手术切除标本进行抗人β促绒膜性腺激素（βＨＣＧ）多克隆抗体和抗因子ＦⅧ相关抗原抗体（ＦⅧＲＡｇ）免疫组织化学染色,观察癌组织、癌旁、正常组织各区域βＨＣＧ的表达和ＭＶＤ。结果所有胃癌组织中,βＨＣＧ仅在癌细胞内阳性表达,表达率为３７．５％（１５／４０）。ＭＶＤ在癌组织为２７．４±７．１,癌旁为１１．９±５．４,正常组织为４．８±１．５（Ｐ＜０．０５～０．０１）。βＨＣＧ阳性组的ＭＶＤ明显高于βＨＣＧ阴性组（Ｐ＜０．０５）,βＨＣＧ,ＭＶＤ和组织类型无关（Ｐ＞０．０５）,但βＨＣＧ和淋巴结转移有关（Ｐ＜０．０５）,伴有血道转移组的βＨＣＧ,ＭＶＤ均高于不伴血道转移组（Ｐ＜０．０５）。结论微血管生长与肿瘤的生长,血道转移有关,而ＨＣＧ对肿瘤的微血管有一定的促生长作用。     

人肝细胞癌及癌周组织中p53、c-myc基因的表达及临床意义

目的：探讨ｐ５３及ｃｍｙｃ基因表达在原发性肝细胞癌（ＨＣＣ）发生发展过程中的作用。方法：应用免疫组织化学方法分别检测７３例和６０例ＨＣＣ癌及其癌周组织中ｐ５３和ｃｍｙｃ基因的表达状况。结果：ｐ５３基因在ＨＣＣ中阳性表达率显著高于癌周组织（Ｐ＜０．０５,）,癌周组织中ｐ５３基因表达仅见于癌周增生结节,癌周肝硬变及正常肝组织内未见ｐ５３基因阳性表达;ｃｍｙｃ基因的阳性表达率在ＨＣＣ与癌周增生结节中相近（Ｐ＞０．０５）,且两者均显著高于癌周肝硬变和正常肝组织（分别为Ｐ＜０．０５,Ｐ＜０．０１）;ｐ５３及ｃｍｃｙ基因表达均与ＨＣＣ分化程度呈显著正相关,低分化组ｐ５３及ｃｍｙｃ基因的阳性表达率均显著高于高分化组（Ｐ均＜０．０５）。结论：ｐ５３及ｃｍｙｃ基因过度表达均参与了人肝细胞癌的发生发展过程;癌周增生结节属癌前期病变,与肝癌的发生有关。     

大肠癌内分泌样癌细胞分化与p53蛋白聚集变化关系的研究

采用免疫组织化学ＡＢＣ法检测６６例经１０％福尔马林固定，石蜡包埋的大肠癌手术切除癌组织中的嗜铬蛋白Ａ（ＣｈｒｏｍｏｇｒａｎｉｎＡ，ＣＧＡ）表达及ｐ５３蛋白聚集，并定量计数ｐ５３免疫阳性细胞，进一步分析ＣＧＡ与ｐ５３蛋白聚集变化的关系，结果显示：大肠癌ｐ５３ＣＧＡ阳性率分别为６１％（４０／６６）和３８％（２５／６６）；ＣＧＡ阳性及阴性病例ＣＧＡｐ５３阳性率分别为８０％（２０／２５）和４９％（２０／４１），ＣＧＡ阳性肿瘤ｐ５３阳性率明显高于ＣＧＡ阴性肿瘤（χ２＝６．３４，Ｐ＜０．０２５）；ｐ５３、ＣＧＡ均阳性的大肠癌２０例ｐ５３阳性细胞数为８５７±７０６／ｍｍ２，ｐ５３阳性、ＣＧＡ阴性表达者２０例ｐ５３阳性细胞数５７１±４７８／ｍｍ２，前者高于后者（ｔ＝２．３３，Ｐ＜０．０５）。结论：ｐ５３蛋白聚集与内分泌样癌细胞的分化呈现较明显的一致性，这种ｐ５３肿瘤抑制基因的变化可能是影响大肠癌内分泌样癌细胞分化的重要分子学改变     

ＴＧＦβ１与Ｓｍａｄ４基因在肝细胞癌中的表达及意义

目的：通过检测ＴＧＦβ１与Ｓｍａｄ４基因在肝细胞癌（ＨＣＣ）中的表达,初步探讨ＴＧＦβ／Ｓｍａｄ信号通路中ＴＧＦβ１与Ｃｏ-Ｓｍａｄ（Ｓｍａｄ４）与ＨＣＣ的发生、发展之间的可能关系。方法：采用免疫组化ＡＢＣ法及原位杂交法（ＩＳＨ）检测４１例ＨＣＣ组织切片中癌与癌旁ＴＧＦβ１、Ｓｍａｄ４蛋白、Ｓｍａｄ４ ｍＲＮＡ的表达,５例外伤性肝破裂手术切除标本作正常对照。比较ＨＣＣ组与对照组及ＨＣＣ癌组织与癌旁组织ＴＧＦβ１与Ｓｍａｄ４蛋白、Ｓｍａｄ４ｍＲＮＡ表达的差异。结果：正常对照组ＴＧＦβ１呈阴性表达,Ｓｍａｄ４蛋白、Ｓｍａｄ４ｍＲＮＡ均呈阳性表达;ＴＧＦβ１在ＨＣＣ组织中阳性表达率为７８.０％（３２／４１）,在癌旁组织中为95.１％（３９／４１）,两者比较差异显著（Ｐ＜０.０５）;Ｓｍａｄ４蛋白在ＨＣＣ组织中阳性表达率为４８.８％（２０／１）,在癌旁组织中为７８.０％（３２／４１）,两者比较有显著差异（Ｐ＜０.０１）;Ｓｍａｄ４ｍＲＮＡ在ＨＣＣ组织中阳性表达率为５１.２％（２１／４１）,在癌旁组织中为７３.１％（３０／４１）,两者比较有显著差异（Ｐ＜００５）;与正常肝组织比较,ＨＣＣ组织中Ｓｍａｄ４蛋白和Ｓｍａｄ４ｍＲＮＡ阳性表达均显著降低（Ｐ＜０.０５）;Ｓｍａｄ４ｍＲＮＡ在ＨＣＣ组织中阳性表达在病理分级Ⅰ、Ⅱ级与Ⅲ、Ⅳ级之间存在显著差异（Ｐ＜０.０５）,Ⅲ、Ⅳ级阳性表达较Ⅰ、Ⅱ级降低;癌旁组织中Ｓｍａｄ４蛋白的阳性面积百分比、吸光度及Ｓｍａｄ４ｍＲＮＡ的阳性面积百分比均显著高于ＨＣＣ组织中（Ｐ＜０.０５）。ＨＣＣ中Ｓｍａｄ４蛋白、Ｓｍａｄ４ｍＲＮＡ与ＴＧＦβ１比较均存在显著差异（Ｐ＜０.０５）,但均无显著相关性（Ｐ＞０.０５）。结论：ＴＧＦβ１过表达、Ｓｍａｄ４表达缺失可能在ＨＣＣ的发生、发展中发挥重要作用。     

蛙皮素在胃癌,癌旁粘膜中的表达及其意义探讨

应用免疫组织化学技术对１６１例进展期胃癌行嗜铬粒蛋白Ａ（ＣｇＡ）抗体染色。将检出有ＣｇＡ阳性癌细胞的胃癌７３例，癌旁粘膜６３例行蛙皮素（Ｂｏｍｂｅｓｉｎ，ＢＯＭ）及胃泌素（Ｇａｓｔｒｉｎ，ＧＡＳＴ）抗体染色。应用图像分析系统对癌旁粘膜内分泌细胞进行定量测量。结果显示７３例ＣｇＡ阳性胃癌中１５例ＢＯＭ呈阳性表达，ＢＯＭ阳性胃癌均为分化差的胃癌。癌旁胃窦粘膜无萎缩组，ＢＯＭ阳性细胞平均计数较正常对照组明显增多（Ｐ＜０．０１），癌多为弥漫型癌（８５％）．蛙皮素在胃癌及癌旁粘膜中的表达与胃泌素相似。提示蛙皮素刺激胃癌生长的作用，可能部分是通过刺激胃泌素的释放，部分是直接作用于肿瘤细胞。     

膀胱移行细胞癌中碱性成纤维细胞生长因子表达的意义

目的 探讨膀胱移行细胞癌中碱性成纤维细胞生长因子（ｂＦＧＦ）的表达及其与临床病理指标的关系。方法 采用免疫组织化学方法，对８例正常膀胱组织及６２例原发性膀胱移行细胞癌中的ｂＦＧＦ进行检测。结果 膀胱移行细胞癌组织中ｂＦＧＦ阳性表达率为４６．８％。低分化癌和浸润性癌中的ｂＦＧＦ阳性表达率明显高于高分化癌和浅表性癌（Ｐ〈０．０５），复发者的阳性表达率明显高于未复发者（Ｐ〈０．０５），ｂＦＧＦ阳性表达者     

p21和PCNA在喉原发性鳞癌中的表达

为探讨ｐ２１、ＰＣＮＡ在喉鳞癌中表达及其与临床的关系，采用免疫组化ＬＳＡＢ方法对３７例喉原发性鳞癌、癌旁１．０ｃｍ组织及２０例声带息肉组织进行ｐ２１和ＰＣＮＡ的检测，结果显示：ｐ２１表达定位于胞浆，癌旁组中有３例软骨细胞出现胞核阳性。喉癌组与癌旁组及声带息肉组的表达率相比较，Ｐ＜０．０５。组织分化高者ｐ２１表达高，组织分化低者ＰＣＮＡ表达高，高、低分化者表达率相比较，Ｐ均＜０．０５。但ｐ２１与ＰＣＮＡ二者无明显负相关。有颈淋巴结转移者的ＰＣＮＡ表达明显高于未转移者，Ｐ＜０．０５。作者认为，ｐ２１和ＰＣＮＡ在喉癌细胞的生长调控中可能起着重要作用。     

Undifferentiated carcinoma of the gallbladder. A clinicopathologic, histochemical, and immunohistochemical study of 21 patients with a poor prognosis

Among 284 cases of carcinoma of the gallbladder, 21 were identified as undifferentiated carcinoma (UC), with little glandular or other specific epithelial differentiation. These tumors were classified into three histologic types according to the components: (1) small cell type (eight cases); (2) pleomorphic cell type (eight cases); and (3) spindle cell or pseudosarcomatous type (five cases). Histochemical and immunohistochemical study by the immunoperoxidase technique revealed that most of the tumors (13/21) contained mucosubstances, and that all examples of the UC were immunoreactive for epithelial membrane antigen (EMA), keratin, and carcinoembryonic antigen (CEA), thereby indicating the epithelial nature of the neoplastic cells. Vimentin immunoreactivity was found in nine tumors. In 19, the tumor contained various neoplastic endocrine cells, including somatostatin-immunoreactive (14/19), gastrin-immunoreactive (14/19), human chorionic gonadotropin (HCG)-immunoreactive (9/19), pancreatic polypeptide-immunoreactive (4/19), and serotonin-immunoreactive cells (4/19). The prognosis of patients with UC of the gallbladder was poorer than that of patients with differentiated adenocarcinoma.     

p27和cyclin E在胆囊癌中表达及与临床病理关系的研究

目的 :探讨p2 7蛋白及细胞周期素E(cyclinE)与胆囊癌发生和发展的关系。方法 :应用免疫组化SABC法检测 5 4例胆囊癌、4 8例胆囊腺瘤及 5 0例胆囊正常黏膜中p2 7及cyclinE表达情况 ,同时结合临床病理资料进行分析。结果 :5 4例胆囊癌中 ,8例 (15 % )p2 7高表达 ,4 4例 (81 4 8% )cyclinE表达 ;4 8例胆囊腺瘤中 ,2 9例 (6 0 % )p2 7高表达 ,2 7例 (5 6 2 5 % )cyclinE表达 ;5 0例胆囊正常黏膜中 ,35例 (70 % )p2 7高表达 ,2 6例 (5 2 % )cyclinE表达。p2 7蛋白在胆囊癌中的表达明显降低 ,三者之间差异有极显著意义 ,P <0 0 0 5。另外 ,p2 7在胆囊癌中表达与癌细胞的分化程度差异有显著意义 ,P <0 0 5 ;低分化癌p2 7表达较低 ,高分化与低分化的p2 7表达差异有显著意义 ,P <0 0 5。p2 7低表达的患者 1年生存率显著降低。cyclinE在胆囊癌中表达与癌细胞的分化程度和肿瘤的病理分期有关。p2 7和cyclinE在胆囊癌中表达存在着相反的联系。结论 :p2 7是细胞周期的负调控因子和潜在的肿瘤抑制因素。p2 7蛋白的降低和cyclinE的过表达在胆囊癌的发生中可能起着重要作用。p2 7是胆囊癌预后的一个可靠指标。     

PTEN和p16基因蛋白在胆管癌和胆囊癌中表达的研究

目的探讨PTEN和p16抑癌基因在胆管癌和胆囊癌组织中的阳性表达及意义。方法用S-P免疫组化法测定PTEN、p16基因蛋白在63例胆管癌及胆囊癌石蜡标本的阳性表达率。结果胆管癌PTEN和p16阳性表达为42.4%和36.3%,低于胆囊癌的43.3%和46.6%(P>0.05);胆囊癌组低分化组p16表达明显低于高、中分化组(P<0.05);PTEN表达与分化程度差异无显著性(P>0.05),结论p16和PTEN基因在胆道恶性肿瘤组织中呈低表达,表明胆道恶性肿瘤的发生及发展有多基因变异或缺失。     

MUC1和MUC16在胆囊癌中的表达及临床意义

目的:研究MUC1和MUC16在正常胆囊黏膜、胆囊腺瘤及胆囊癌中的表达情况,以及胆囊癌中MUC1和MUC16的表达与胆囊癌Nevin分期及组织分化程度的关系。方法 :收集因胆囊息肉行胆囊切除术病例60例、胆囊腺瘤病例60例及胆囊癌病例60例,进行MUC1和MUC16的免疫组织化学染色,结合病理图像,分析其在正常胆囊黏膜组织、胆囊腺瘤及胆囊癌中的表达情况。结果:MUC1在正常胆囊黏膜组、胆囊腺瘤组和胆囊癌组中,阳性表达率分别为6.67%、38.33%、81.67%。MUC16在正常胆囊黏膜组和胆囊腺瘤组中,无阳性表达。在胆囊癌组中,阳性表达率为36.67%。MUC1和MUC16在Nevin分期 I期组、II期组、III期及III期以上组中,阳性表达率分别为62.50%、80.00%、95.83%和18.75%、30.00%、54.17%。MUC1和MUC16在高分化组、中分化组、低分化组中阳性表达率分别为60.00%、78.95%、96.15%和13.33%、26.32%、57.69%。结论:MUC1和MUC16的阳性表达在胆囊癌的发生发展中起着重要作用,MUC1和MUC16的阳性表达促进胆囊癌的发生发展。MUC1和MUC16作为一种胆囊癌的肿瘤标志物,并且预示胆囊癌的恶性程度及浸润程度。     

Placental proteins in high-grade urothelial neoplasms. An immunohistochemical study of human chorionic gonadotropin, human placental lactogen, and pregnancy-specific beta-1-glycoprotein

We examined the presence of human chorionic gonadotropin (HCG) in 16 low-grade and 47 high-grade urothelial neoplasms, including two cases with trophoblastic-like differentiation. In HCG-positive tumors, the presence of human placental lactogen (HPL) and pregnancy-specific beta-1-glycoprotein (SP-1) also was assessed. HCG immunoreactive cells were found in nine of the 47 high-grade tumors (19%), whereas none of the low-grade tumors were positive for HCG. This hormone was predominantly detected in the most undifferentiated and pleomorphic areas; however, HCG-positive cells also were found in areas of carcinoma in situ and well-differentiated transitional cell carcinoma in two cases. The serum HCG level was increased in two of the four cases studied. HPL and SP-1 immunoreactive cells were observed in seven and five cases, respectively, and it was found that tumors positive for SP-1 also were positive for HPL. Five tumors, including the two with trophoblastic differentiation, contained the three placental proteins. The HPL and SP-1 immunostained cells were usually found in the same areas of the tumor that were positive for HCG, but there was always a lower number of HPL and SP-1 immunoreactive cells than HCG immunoreactive cells. In one case, HPL and SP-1 could be found in areas of well-differentiated transitional cell carcinoma. These findings suggest that the morphologic and functional trophoblastic differentiation in urothelial carcinomas is a progressive phenomenon evolving from transitional cell carcinomas.     

人胎盘GST－π抗体的免疫组织化学检测对胆囊癌早期诊断的意义

应用人胎盘型谷胱甘肽Ｓ—转移酶（ＧＳＴ－π）抗体的ＡＢＣ法免疫组织化学技术，检测了１００例胆囊良、恶性病变组织的ＧＳＴ－π活性，结果表明，２２例正常胆囊粘膜对照组ＧＳＴ－π阳性率为９％，１２例胆囊炎和４例胆囊腺瘤ＧＳＴ－π阳性率分别为１６．６７％和２５％，视为癌前病变的异型增生组，ＧＳＴ－π阳性率达１００％，随着异型增生程度加重，ＧＳＴ－π活性增强。３８例胆囊腺癌ＧＳＴ－π阳性率为８７％，其中高分化和中分化型腺癌组织中ＧＳＴ－π阳性率为９５％，低分化型为１００％，未分化型腺癌ＧＳＴ－π阳性率７５％，胆囊腺癌、异型增生组ＧＳＴ－π阳性率及平均强度都显著高于良性病变和正常对照组（Ｐ＜Ｏ．０１）。因此，ＧＳＴ－π的免疫组织化学检测可作为胆囊癌及癌前病变的一项新的早期诊断指标。     

Analysis of KIT (CD117) expression in gallbladder carcinomas by tissue microarray.

AIMS: KIT (CD117) is a transmembrane tyrosinase-kinase receptor which has been related to cell proliferation, differentiation, adhesion and control of apoptosis. If present, KIT may provide a suitable target for tumour therapy. In this study, we report the presence of KIT in primary and metastatic gallbladder carcinomas. METHODS: Formalin-fixed and paraffin-embedded specimens of 57 primary gallbladder carcinomas and 18 corresponding metastases were stained using a tissue microarray technique and two different antibodies. RESULTS: Only three tumours stained for KIT. With a polyclonal antibody only one well differentiated papillary adenocarcinoma was immunoreactive. With a monoclonal antibody two additional poorly differentiated tubular adenocarcinoma showed weak and focal immunostaining. CONCLUSIONS: KIT immunoreactivity is infrequent in gallbladder carcinoma. Thus, routine screening of tumour tissues for KIT by immunohistochemistry appears to be cost-ineffective and cannot be recommended. Moreover, the lack of substantial KIT immunoreactivity in both primary and metastatic gallbladder carcinoma tissues does not provide a rationale to investigate imatinib mesylate therapy in clinical trials including patients with advanced disease.     

Establishment of a human chorionic gonadotropin-producing human gastric carcinoma in nude mice

A human chorionic gonadotropin (HCG)-producing gastric carcinoma was transplanted into BALB/c nu/nu nude mice. The original tumor tissue had been obtained by gastrectomy from a 55-year-old patient with gastric carcinoma. The tumor was transplanted serially in nude mice, and its doubling time was stable to approximately 12 days. A positive correlation was observed between serum HCG level and tumor weight. The serum HCG level of the mice and the histology of the tumor weight. The serum HCG level of the mice and the histology of the tumor, papillary adenocarcinoma with partial poorly differentiated adenocarcinoma, did not change on serial transfers. HCG was positively stained by an immunochemical technique only in the site of the poorly differentiated adenocarcinoma, while staining was negative in the site of the papillary adenocarcinoma, which constituted most of the tumor. These results indicate that this tumor in nude mice will be useful not only as a therapeutic experimental system but also for studying the potential malignancy of HCG-producing cancer cells.     

Gallbladder carcinoma in a pregnant patient with Crohn's disease complicated with gallbladder involvement

Primary gallbladder (GB) carcinoma and Crohn’s disease (CD) of the GB are individually rare. We present a case of a pregnant woman with CD found to have GB involvement and primary GB carcinoma. A 34-year-old female at 6 wk gestation with a 21 year history of CD of uncertain extent presented with 3 mo of diarrhea, urgency and abdominal pain. During work-up, she was found to have elevated transaminases and an abnormal alkaline phosphatase. Imaging revealed two gallbladder polyps both greater than 1 cm in size. Resection and histological evaluation was consistent with Crohn’s involvement of the GB, poorly differentiated adenocarcinoma of the GB with invasion through the muscularis propria and matted lymph nodes in the porta hepatis positive for metastatic carcinoma (stage pT2N1). Six cases of CD involving the GB, two cases of primary GB carcinoma in CD, and ten cases of cholangiocarcinoma in pregnancy have been published. This is the only case that describes all three factors. Common features in CD of the GB include acute cholecystitis, ileal involvement, and presence independent of active intestinal disease. Common features in CD patients with GB malignancy include younger age of detection, a long history of CD, extensive colonic and ileal involvement of disease, the absence of cholelithiasis, and pre-existing gallbladder disease (primary sclerosing cholangitis and gallbladder polyps). Pregnancy is specific to this case. The role of CD in the development of GB malignancy is not well understood nor is the contribution of pregnancy to the spread of disease. Chronic inflammation and immunosuppression compounded by hormonal influence is implicated.     

Adenosquamous Carcinoma of the Gallbladder: A Clinicopathological, Immunohistochemical and Flow-cytometric Study of Twenty Cases

Twenty patients (7.4%) with adenosquamous carcinoma of the gallbladder were selected from 271 surgically resected gallbladder cancers. The 20 patients were composed of 8 men and 12 women with a mean age of 66.9 years. Histologically, all twenty tumors showed an abrupt transition between the adenocarcinoma (AC) and squamous cell carcinoma (SCC) areas, and well differentiated AC was also found in the peripheral area of the tumor. A histochemical and immunohistochemical study using alcian blue, periodic acid-Schiff, cytokeratins, involculin and tissue polypeptide antigen disclosed a different nature of the two components. DNA heterogeneity between the components was detected in 5 of 7 cases by flow cytometry. The positive rate of immunostaining for proliferating cell nuclear antigen in the SCC areas (mean 20.55%) was larger than that of the AC areas (mean 11.40%) ( P =0.0029), which indicated that the SCC areas had a greater proliferative capacity than AC areas. These results suggest that the SCC component of adenosquamous carcinoma of the gallbladder arose by a stepwise molecular progression of the pre-existing AC. Furthermore, the prognosis of adenosquamous carcinomas of the gallbladder (mean survival: 10 months) in the advanced stage (pTNM 2–4) was less favorable than those of papillary and well differentiated AC (mean survival: 99 months and 86 months) ( p <0.0001).