Fascin与Ki-67在分化差的非小细胞肺癌中的表达

目的观察Fascin与Ki-67在非小细胞肺癌中的表达情况,探讨其表达与肿瘤生物学行为及临床病理指标的关系。方法对选自2004-06~2005-02北京协和医院病理科档案的肺叶切除标本对51例不同组织学类型及临床分期的非小细胞肺癌进行Fascin和Ki-67免疫组化染色,分别计算Fascin的阳性率及Ki-67指数,统计分析不同病理特征的差异。结果51例非小细胞肺癌中,Fascin的总阳性率为52.9%,其中2例高分化的黏液表皮样癌和4例支气管肺泡癌Fascin表达均为阴性,而4例大细胞癌和3例多形性癌Fascin表达阳性;腺癌中Fascin阳性率为43.5%,而在鳞癌中阳性率为66.7%。随着癌分化程度的降低,Fascin的阳性率上升,统计学分析有极显著性差异(P<0.01)。Ki-67的阳性表达与肿瘤的分化程度呈正相关,且Fascin阳性组的Ki-67指数显著高于阴性组。除Fascin表达在男性病人较高外,没有其它临床病理特征的相关性。结论Fascin在分化差的NSCLC中表达上调,与Ki-67指数呈正相关。Fascin是NSCLC分化差、恶性度高的标记。     

甲状腺肿瘤bax和Ki-67的表达及意义

目的探讨bax和Ki-67抗原在甲状腺肿瘤组织中的表达及意义。方法选择手术切除的甲状腺癌56例、甲状腺腺瘤13例、腺瘤旁正常甲状腺组织10例,采用免疫组织化学S-P法及原位细胞凋亡技术,观察bax、Ki-67的表达情况,结合临床病理资料进行统计学分析。结果正常甲状腺、甲状腺腺瘤和甲状腺癌组织中bax阳性表达率分别为90．0％、61．54％和28．57％,Ki-67阳性表达率分别为0．23．08％和69．64％,甲状腺癌bax表达降低、Ki-67表达增高（P〈0．05）。甲状腺癌bax表达与病理类型、病理分期、淋巴结转移有关（P〈0．05）,Ki-67的表达与病理分期、淋巴结转移有关（P〈0．05）。结论bax和Ki-67表达异常对预测甲状腺癌转移和评估预后具有重要参考价值。     

The actin-bundling protein Fascin is overexpressed in inflammatory bowel disease and may be important in tissue repair

Background  

Fascin is associated with increased cell motility in colorectal tumours but is absent from the normal colonic epithelium. We examined the expression of fascin in inflammatory bowel disease (IBD) and its location at regions undergoing restitution and regeneration. Tissue repair is essential for disease remission and we sought to determine the effects of therapeutic modalities on fascin expression and function using an in vitro model.     

Risk factors for lymph node metastasis of submucosal invasive differentiated type gastric carcinoma: clinical significance of histological heterogeneity

Background. The use of endoscopic resection for submucosal invasive gastric carcinoma (Sm-ca) with histologically differentiated type has been expected. However, the treatment criteria remain controversial. The purpose of this study was to clarify the relationship between lymph node metastasis and the histologic features of differentiated Sm-ca. Methods. The clinicopathologic features of 35 patients with node-positive differentiated Sm-ca were compared with those of 221 patients with node-negative differentiated Sm-ca by multivariate analysis with logistic regression. To clarify the metastatic behavior of differentiated Sm-ca, we examined mucin-histochemical expression and immunohistochemical staining, using Ki-67, p53, and c-erbB2. Results. The rate of lymph node metastasis was significantly higher in differentiated Sm-ca with histologi-cal heterogeneity (combined differentiated type, with poorly differentiated component) than in that without histological heterogeneity (27% vs 7%; P < 0.001). Multivariate analysis revealed that lymphatic vessel invasion was the most significant determinant (odds ratio, 8.68) for lymph node metastasis. Histological heterogeneity (odds ratio, 3.88) was next, followed by papillary adenocarcinoma (odds ratio, 3.28), and submucosal invasion level (odds ratio, 2.34). The mean value of the Ki-67 labeling index for node-positive differentiated Sm-ca was higher than that of node-negative differentiated Sm-ca (47% vs 39%; P < 0.05). Conclusions. When the extension of endoscopic surgery to differentiated Sm-ca is considered, this therapeutic technique should be limited to the differentiated type of Sm-ca without histological heterogeneity. The Ki-67 labeling index provides useful information for identifying those patients with a high risk of lymph node metastasis. Received: January 9, 2001 / Accepted: April 13, 2001     

Ki-67 expression as a prognostic marker in patients with hepatocellular carcinoma

Ki-67 expression in tumours has been shown to be associated with prognosis in patients with hepatocellular carcinoma (HCC). In this study, primary HCC samples were obtained from 67 patients undergoing surgical resection. None of these patients had been subjected previously to any other form of therapy, such as arterial embolization or chemotherapy. Histologically normal liver tissues from liver resection for metastatic colon cancer were taken as controls (n= 8). Monoclonal antibody against Ki-67 was used for immunostaining and ?ow cytometry was used to measure tumour DNA ploidy. The mean Ki-67 labelling index (percentage of Ki-67-positive cells) of the HCC (26 ± 22%; range 0.1–89%) was signi?cantly higher than that of the normal controls (39 ± 0.8%, P < 0.05). The mean Ki-67 labelling index (19 ± 15%; n= 28) of the tumours with diploid DNA pattern was signi?cantly lower than those with aneuploid DNA pattern (32 ± 25%, n= 39; P= 0.01). Hepatocellular carcinoma patients (n= 47) with Ki-67 index >10% had a signi?cantly lower disease-free and overall survival than those (n= 20) with Ki-67 index ≤10% (P= 0.0009 and P= 0.02, respectively). Multivariate analysis showed that Ki-67 expression and tumour node metastasis stage were two independent prognostic factors for disease-free and overall survival rates. Our results suggest that the expression of Ki-67 is an independent prognostic indicator for patients with HCC after resection and could be of assistance in the decision-making of adjuvant therapy.     

Differences in tumor cell proliferation, HLA DR expression and lymphocytic infiltration in various types of thyroid carcinoma.

The proliferative activity of various thyroid carcinoma forms (papillary, follicular, medullary, anaplastic) was investigated using two second generation antibodies against Ki-67 that can be used on paraffin-embedded sections. Poorly-differentiated carcinomas had a higher proliferation than well-differentiated forms. Papillary carcinoma stained significantly more often with either antibody than follicular carcinoma. A solid growth pattern correlated with high Ki-67 expression while an increase in follicular elements and a high amount of psammoma bodies coincided with lower proliferation.HLA class II expression and infiltrating lymphocytes are prerequisites for an immune defense against cancer. In this study, HLA DR was increased in poorly-differentiated carcinomas, especially in the anaplastic type. The increase in HLA DR was correlated with Ki-67 positivity. On tumor-infiltrating lymphocytes, HLA DR was well expressed in papillary carcinoma and relatively poorly expressed in follicular carcinoma, but there was no significant correlation with carcinoma type or morphological parameters. CD 45 R0, which might recognize memory cells, was found mostly in anaplastic and papillary carcinomas, and correlated well with HLA DR expression. These findings imply that an active but variable immune response is present in thyroid carcinoma.     

胰腺癌组织Survivin与Ki-67的表达及其意义

目的:探讨Survivin和Ki-67在胰腺癌组织中的表达及其与临床病理特征的关系．方法:采用免疫组织化学技术检测各期胰腺癌86例及癌旁组织78例中Survivin和Ki-67的表达水平,并结合病理特征进行分析。结果:胰腺癌旁组织或良性肿瘤旁组织不表达Survivin 蛋白．胰腺癌组织Survivin阳性表达率为87．9％,显著高于胰岛细胞癌(12．7％)或胰岛细胞瘤(5．2％)(P<0．01),而且Survivin表达程度与肿瘤分化程度、淋巴结转移相关(P<0．05)．Ki-67蛋白在胰腺癌组织中阳性表达率为 94．4％,显著高于胰岛细胞癌或胰岛细胞瘤组(P<0．01), 并与胰腺癌组织分化程度相关(P<0．05)．两种蛋白表达有高度相关性(r=0．87)．结论:Survivin和Ki-67在胰腺癌组织中过表达,并且与胰腺癌病理特征密切相关．Survivin可能是反应胰腺癌预后不良的指标．     

Intraductal neoplasm of the intrahepatic bile duct: clinicopathological study of 24 cases

AIM: To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS: Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ , high grade including tumors with microinvasion). RESULTS: Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION: Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.     

大肠癌免疫组化表达与临床病理的关系

目的:探讨大肠癌CEA、P53、nm23、Ki-67、MRP免疫组化表达特点和相互关系,及其与临床病理的关系．方法:回顾性分析2003-01／2006-07我院收治的73例大肠癌患者的临床病理及随访资料,并对其石蜡标本采用免疫组化SP染色法检测CEA、P53、nm23、Ki-67、MRP,分析其免疫组化特点及其与临床病理之间的关系．结果:CEA、P53、nm23、Ki-67、MRP在大肠癌中的阳性表达率依次为82．2％、68．5％、75.3％、84．9％和64．4％．CEA、MRP与大肠癌患者的各因素无统计学差异．P53、Ki-67和nm23与肿瘤的Dukes分期和淋巴结转移有关, P53、Ki-67在Dukes C、D期的阳性表达率(依次为82．8％和100％1明显高于Dukes A、B期者(59．1％和75．0％)(P<0．05),而nm23在Dukes C、D期的阳性表达率(58．6％)明显低于Dukes A、B期者(86．4％)(P<0．05)．CEA与nm23的表达呈明显的负相关(r=-0．296,P=0．011),而P53和Ki-67表达之间呈现明显的正相关(r= 0．308,P=0．008),其他各指标间的表达无相关性．nm23、P53和Ki-67与预后因素关系明显,nm23在生存期≥3 a患者的阳性表达率(92．9%)高于生存期<3 a者(71．2％)(P<0．05),而P53和Ki-67在生存期≥3 a患者的阳性表达率(依次为42．9％和64.3％)明显低于生存期<3 a者(74．6％和89．8％)(P<0．05)．结论:P53、Ki-67和nm23的表达与大肠癌的侵袭转移和预后密切相关．CEA可能是大肠癌的侵袭转移的促进因素．MRP所引起的耐药机制是一个相对独立的机制．CEA、P53、nm23、Ki-67可作为判断大肠癌恶性程度、侵袭转移以及预后的指标．     

Ki-67 labeling index as an independent prognostic factor in human esophageal squamous cell carcinoma

Background

Although the Ki-67 labeling index (LI) is frequently used to determine the proliferative activity of malignant tumors, no consensus has been reached about its clinicopathological significance in esophageal squamous cell carcinoma (ESCC). In this study, we sought to determine an adequate Ki-67 LI cutoff value and investigated its prognostic significance in ESCC.

Methods

The Ki-67 LI was calculated by immunohistochemistry for 49 primary tumor samples obtained from ESCC patients who had undergone curative esophagectomy, and the correlations between the Ki-67 LI and various clinicopathological features or prognosis were analyzed.

Results

The Ki-67 LI of the tumors ranged from 5.3 to 55.9?%. The mean Ki-67 LI increased from 27.4?% in pN0 tumors to 40.3?% in pN3 tumors. The 5-year survival rate decreased as the Ki-67 LI increased. When the patients were divided into two groups using an Ki-67 LI cutoff value of 35?%, the 5-year survival rate of the patients with Ki-67 LI of <35?% was 82.9?%, which was significantly higher than that of the patients with Ki-67 LI of ??35?% (35.7?%). The percentage of pN-positive tumors was significantly higher among the patients with Ki-67 LI of ??35?% (85.7?%) than in patients with Ki-67 LI of <35 (48.6?%). Multivariate analysis demonstrated that pT and pN categories and the Ki-67 LI were independent prognostic factors.

Conclusions

These observations indicate that the Ki-67 LI is correlated with lymph node metastasis and can be used as an independent prognostic factor for ESCC patients by selecting an adequate cutoff value.     

Ki-67和P21在肾上腺皮质癌中的表达及意义

目的　探讨肾上腺皮质癌 (ACC)中Ki 67和P2 1的表达及其意义。方法　采用免疫组化SP法和图像分析技术对 8例正常肾上腺组织、2 0例肾上腺腺瘤 (ACA)、19例肾上腺皮质癌中Ki 67、P2 1进行检测。结果　Ki 67和P2 1的表达在肾上腺腺瘤与肾上腺皮质癌间差异均有统计学意义 (P <0 .0 1,P <0 .0 5 )。Ki 67的表达与肾上腺皮质癌分期、浸润或转移、2年生存情况相关(P <0 .0 1) ,与肿瘤大小无关 (P >0 .0 5 )。P2 1的表达与肾上腺皮质癌的大小、分期、浸润或转移、2年生存情况均无显著相关 (P >0 .0 5 )。结论　Ki 67和P2 1对肾上腺皮质良恶性肿瘤具有重要的鉴别诊断作用 ,Ki 67可作为判断肾上腺皮质癌预后不良的指标。     

Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas

BackgroundMalignant intraductal papillary mucinous neoplasm (IPMN) has poor prognosis. The carcinogenesis of IPMN is not clear. The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis.MethodsBy using immunohistochemistry, we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013. We also examined the expression of Ki-67, c-Myc and p-JNK.ResultsThe median immunostaining index of pSmad3C was 79.2% in low-grade dysplasia, 74.9% in high-grade dysplasia, and 42.0% in invasive carcinoma (P < 0.01), whereas that of pSmad3L was 3.4%, 4.3%, and 42.4%, respectively (P < 0.01). There was a negative relationship between the expression of pSmad3C and c-Myc (P < 0.001, r = -0.615) and a positive relationship between the expression of pSmad3L and c-Myc (P < 0.001, r = 0.696). Negative relationship between the expression of pSmad3C and Ki-67 (P < 0.01, r = -0.610) and positive relationship between the expression of pSmad3L and Ki-67 (P < 0.01, r = 0.731) were confirmed. p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells. The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58 (range, 0.05–0.93), 3.83 (range, 0.85–5.96), respectively (P = 0.02). The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91 (range, 0–36.9) and 82.1 (range, 46.2–97.1), respectively (P = 0.02). The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9 (range 5.7–30.8) and 90.9 (range 52.9–98.5), respectively (P = 0.02).ConclusionspSmad3L was upregulated in malignant IPMN. pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.     

原发性胆囊癌组织中脆性组氨酸三联体基因和Ki-67的表达及临床意义

目的:探讨脆性组氨酸三联体(FHIT)基因和Ki-67抗原在原发性胆囊癌、胆囊腺瘤和慢性胆囊炎组织中的表达情况.方法:应用免疫组织化学S-P法,检测51例原发性胆囊癌、15例胆囊腺瘤和12例慢性胆囊炎组织中FHIT和Ki-67的表达情况,并分析其与胆囊癌临床病理因素的关系.结果:胆囊癌组中FHIT阳性率明显低于胆囊腺瘤和慢性胆囊炎组(47.1%vs66.7%,91.7%,P<0.01),而Ki-67阳性率明显高于胆囊腺瘤和慢性胆囊炎组(82.4%vs20.0%,0,P<0.01).FHIT表达缺失不仅与胆囊癌的高分级(18.8%vs56.5%,66.7%,P=0.02)、淋巴结或远处转移(33.3%vs66.7%,P=0.019)明显相关,而且与术后生存时间减少关系密切(31.2%vs77.8%,P=0.041).Ki-67表达与胆囊癌的高分级(58.3%vs87.0%,93.8%,P=0.039)和淋巴结或远处转移(33.3%vs66.7%,P=0.037)明显相关.FHIT与Ki-67表达呈负相关(r=-0.285,P=0.043).结论:FHIT基因是胆囊癌的一个候选抑癌基因.FHIT和Ki-67在胆囊癌的发生和演化中均起着重要作用,联合检测FHIT和Ki-67的表达情况有助于临床评估胆囊癌的生物学行为和判断预后.     

运动相关蛋白Fascin在胰腺癌的表达及其临床意义

目的 探讨运动相关蛋白Fascin在胰腺癌的表达及其与临床病理特征的关系.方法 采用RT-PCR法检测SW1990、Patu8988、BxPC3、CfPAC1 4株胰腺癌细胞株Fascin mRNA表达;采用免疫组化方法 检测54例胰腺癌及42例相应癌旁胰腺组织Fascin蛋白表达.结果 胰腺癌细胞株SW1990、Patu8988、CfPAC1有Fascin mRNA表达,BxPC3无表达;54例胰腺癌组织Fascin蛋白表达阳性35例,占64.8%,42例癌旁胰腺组织中均无阳性表达.Fascin蛋白表达与肿瘤分化程度(P<0.01)和淋巴转移(P<0.05)呈显著正相关,但与肿瘤大小及远处转移无相关性(P>0.05).结论 Fascin蛋白在胰腺癌组织中有较高的阳性表达率,检测其表达有助于胰腺癌的诊断,并有助于判断胰腺癌恶性程度.     

Beta human chorionic gonadotropin (β-hCG) expression in pituitary adenomas: relationship to endocrine function and tumour recurrence

The β subunit of human chorionic gonadotropin (β-hCG) is a marker of malignancies. Recent studies have also reported its expression in pituitary adenomas, although its significance is unclear. In this retrospective study, the authors quantitatively investigated the immunohistochemical expression of β-hCG in 123 patients undergoing surgery for pituitary adenomas and explored its relationship to the rest of the endocrine function, tumour recurrence and Ki-67 nuclear labelling. Based on the endocrine profile and immunohistochemistry, the pituitary adenomas were grouped into non-functioning (NFPA; N = 78) and functioning pituitary adenomas (N = 45). The latter included, 20 growth hormone (GH), 12 prolactin (PRL), 8 adreno-corticotrophin hormone (ACTH) and 5 mixed GH-PRL-producing adenomas. Ninety-three (76%) tumours were classified as primary and 30 (24%) tumours classified as recurrent adenomas. Immunohistochemically, 107 (87%) of pituitary adenomas expressed β-hCG, which was more common in NFPA (91%) than functioning pituitary adenomas (80%). β-hCG expression was not different between primary (86%) and recurrent pituitary adenomas (90%) and it was also not related to raised Ki-67 labelling. But, Ki-67 labelling was raised in recurrent pituitary adenomas (33%), compared to primary pituitary adenomas (11%). Although, β-hCG is expressed in the majority of pituitary adenomas, more especially in NFPA, it is un-related to the risk of tumour recurrence or cellular proliferation as measured by Ki-67 nuclear labelling. The high incidence of β-hCG expression in pituitary adenomas may provide a target for specific β-hCG-directed tumour therapies in the future.     

Ki-67 labelling index is related to the risk classification and prognosis of gastrointestinal stromal tumours: a retrospective study

Background and AimsGastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract with malignant potential. The current risk classification standard is unable to accurately evaluate the invasiveness and clinical outcomes of GISTs. Ki-67 labelling index (LI) may be an effective indicator in assessing tumour invasiveness and prognosis, however, its exact value in GISTs is still uncertain. The aims of our study were to evaluate the correlation of the Ki-67 LI and clinicopathological features of GISTs and to assess the potential value of the Ki-67 LI in GISTs classification and prognosis.MethodsThe clinical, pathological and prognostic data were collected and analysed to identify the independent influential factors of GISTs risk stratification and the predictors of GISTs prognosis.ResultsThe Ki-67 LI was significantly associated with the clinicopathological features of tumour progression (P< 0.05). It was an independent influential factor of GISTs risk classification (odds ratio: 1.322; 95% confidence interval: 1.031-1.696) (P = 0.028), and the area under the curve (AUC) value of the Ki-67 LI on the discrimination ability of GISTs risk stratification was 0.906 (P< 0.001). The optimal cutoff value of the Ki-67 LI was 6% (sensitivity of 87.5% and specificity of 76.2%), and patients with Ki-67 LI≥6% exhibited significantly poorer progression-free survival (PFS) than those with Ki-67 LI< 6% (P< 0.001). The AUC value of the Ki-67 LI for predicting PFS in postoperative patients was 0.813 (P = 0.03).ConclusionsThe Ki-67 LI has appreciated value to predict the risk grade and prognosis of GISTs. Patients with Ki-67 LI≥6% are prone to recurrence and metastasis after operation and may need a close follow-up.     

p53 protein expression in intraductal papillary mucinous tumors (IPMT) of the pancreas as an indicator of tumor malignancy

BACKGROUND/AIMS: Intraductal papillary mucinous tumors, as a cystic disease in the pancreas, clinically has a more indolent and favorable course than invasive ductal pancreas carcinoma. However, some cases of intraductal papillary mucinous tumors show invasive and rapid progression like ductal pancreas carcinoma and the prognosis of such patients is sometimes poor. In the current study, we carried out immunohistochemical staining of intraductal papillary mucinous tumor tissues for p53 and investigated whether positive staining indicates tumor malignancies and has a prognostic value for intraductal papillary mucinous tumors. METHODOLOGY: Nineteen (19) patients who underwent pancreatic resection under the diagnosis of intraductal papillary mucinous tumors at the Chiba University Hospital between April 1992 and December 1996 were studied. We performed immunohistochemical staining of p53 as well as of PCNA, Ki-67 and Bcl-2 using their respective antibodies. Pathological findings revealed that 9 cases were intraductal papillary adenoma, 9 were intraductal papillary adenocarcinoma, and one was invasive ductal papillary adenocarcinoma. RESULTS: p53 expression could only be detected in the 1 case with invasive ductal papillary adenocarcinoma. Significant association could not be found between histological features and immunohistochemical staining of PCNA, Ki-67 and Bcl-2. CONCLUSIONS: p53 protein expression could be detected after progression to invasive type of intraductal papillary mucinous tumors. The present results demonstrate that p53 expression might be an indicator of invasive progression in intraductal papillary mucinous tumors, and might represent a surgical indicator of intraductal papillary mucinous tumors.     

Laminin receptors in differentiated thyroid tumors: restricted expression of the 67-kilodalton laminin receptor in follicular carcinoma cells.

The expression of integrin laminin receptors was investigated in normal thyroid primary cultures; immortalized normal thyroid cells (TAD-2); papillary (NPA), follicular (WRO), and anaplastic (ARO) thyroid tumor cell lines; seven thyroid tumors (four papillary and three follicular carcinomas); and normal thyroid glands. The expression of alpha1beta1, alpha2beta1, alpha3beta1, alpha6beta1, and alpha6beta4 was found in all tumor specimens and in tumor cell lines, whereas normal thyroid cells and TAD-2 cells lacked the expression of alpha6beta4. Despite the presence of several integrin laminin receptors, adhesion of TAD-2, NPA, and ARO cells to immobilized laminin-1 was poor, whereas WRO cells and follicular carcinoma-derived cells displayed a strong adhesion. Indeed, WRO and follicular carcinoma-derived cells showed expression of a nonintegrin laminin receptor, the 67-kDa high affinity laminin receptor (67LR). TAD-2, NPA, and ARO cells as well as nodular goiter, toxic adenoma, follicular adenoma, and papillary carcinoma-derived cells did not express the 67LR. Adhesion of WRO and follicular carcinoma-derived cells to laminin-1 was specifically inhibited by a recombinant polypeptide containing laminin-binding domains of 67LR, demonstrating that this receptor confers to follicular carcinoma cells attachment capacity to laminin. Moreover, tissue specimens from follicular carcinomas expressed the 67LR, whereas follicular adenomas and normal thyroid tissues were negative. In thyroid tumors, integrin receptors, although abundant, participate weakly in adhesion to laminin. The expression in follicular carcinoma cells of a functional, high affinity 67LR together with nonfunctional integrin LM receptors could be responsible for the tendency of follicular carcinoma cells to metastasize by mediating stable contacts with basal membranes.     

Survival following resection of pancreatic endocrine tumors: importance of R-status and the WHO and TNM classification systems

Abstract

Objective. The aim of this study was to delineate the clinical outcomes and pathological characteristics of surgically resected endocrine tumors of the pancreas and to determine the importance of the World Health Organization (WHO) and tumor-node metastasis (TNM) classifications, resection status, and Ki-67 expression for long-term survival. Patients and methods. Sixty-nine patients underwent surgical tumor resection with curative intent during 1990–2007. Hospital records were reviewed retrospectively for medical, surgical, pathological, and radiological data. Results. Forty-one patients (59%) had non-functional tumors, 28 (41%) patients had functional tumors. Thirty-seven (54%) tumors were classified as WHO group 1 and the remaining 32 as WHO group 2. There were no poorly differentiated endocrine carcinomas. The overall R0-resection rate was 68%. Patients in whom all gross tumor was resected (R0/R1) had significantly better survival compared to patients with macroscopic residual disease (R2) (p < 0.001). There was no difference in survival between patients with R0 and R1 resections. Both the WHO (p < 0.001) and the TNM (p < 0.001) classifications significantly predicted five and 10-year survival after resection of the primary tumor. Survival analysis revealed significantly better outcome for patients with tumors with Ki-67 index < 2% (p = 0.003). Conclusions. Both WHO and TNM classifications reliably predict long-term survival in patients with resectable pancreatic endocrine tumors. R2 resection status predicted poor prognosis. R0 status did not improve prognosis relative to R1 status. Ki-67 index > 2% is a predictor of poor long-term survival.