Distribution of basement membrane antigens in human esophageal lesions: an immunohistochemical study

The distribution of basement membrane components, type-IV collagen and laminin, was studied immunohistochemically in human samples of normal, hyperplastic, dysplastic and carcinomatous esophageal tissue. The expression of basement membrane components in normal, hyperplastic, and mildly and moderately dysplastic mucosa was characterized by a thick, continuous and linear staining pattern. In severe dysplasia and carcinoma in situ, the basement membrane was thinner and occasionally discontinuous. The distribution of basement membrane in invasive carcinomas varied greatly; well-differentiated, cohesive tumors had a basement membrane, however, poorly-differentiated tumors showing irregular cords, or individual cell infiltration, lacked this membrane at the tumor-stromal interface. Many moderately-differentiated tumors showed probable immature assembly of basement membrane components. The expression of basement membrane was also influenced by the extent of stromal inflammation. The absence or presence (staining pattern) of basement membrane components in esophageal squamous-cell carcinoma did not correlate with the survival rate, but did correlate with the histologic differentiation of epithelial organization.     

Neuroendocrine cells in pancreatic duct adenocarcinoma: an immunohistochemical study

Pancreatic ductal adenocarcinomas can display disseminated neuroendocrine (NE) cells. Controversies exist as to their relative incidence, histogenesis, hormone production, and the prognostic implications of their presence. These issues were elucidated by means of a broad immunohistochemical (IHC) investigation of the resected specimens from 47 patients. Chromogranin A (CgA) was chosen as the major NE marker. In addition, the sensitivity of the conventional IHC procedure was increased by means of the TSA (Tyramide Signal Amplification) technique. In tumours with CgA immunoreactive (IR) cells, detected by the conventional or the TSA methods, these NE cells were further IHC analyzed, using antisera raised against a broad spectrum of neurohormonal peptides, serotonin, and IGF-1. The IHC observations were correlated with clinical and histopathological data, the nuclear IR for the Ki67 antigen (proliferation) of the neoplastic cells, and their IR against the p53 protein. Distinct CgA IR cells were found in 5 out of 47 (11%) tumours when studied by the conventional method, and in 9 out of 47 (19%) when examined by the TSA technique. Corresponding figures, if tumours with only questionable IR against CgA were also included, were 14 (30%) and 23 (50%), respectively. Out of the 9 cases with unequivocal CgA IR, only 3 displayed an IR to an additional hormone or growth factor; this hormone turned out to be somatostatin (only minimal foci). Insulin and glucagon cells also appeared exceptionally. The NE differentiation was found to be unrelated to proliferation, p53 protein expression, and to the survival of the patients. It occurred mainly (7 out of 9) in poorly differentiated adenocarcinomas. Thus, the plain NE immunoprofile of the CgA IR cells, together with the increased IR observed when the TSA technique was used, indicates that the NE cells in these adenocarcinomas are only poorly differentiated. When the CgA IR cells exceptionally become highly differentiated, they can express islet hormones. Using strict structural and IHC criteria, a NE differentiation occurs in less than 20 % of cases; its clinico-pathological significance seems to be non relevant.     

The significance of the HER-2 status in esophageal adenocarcinoma for survival: an immunohistochemical and an in situ hybridization study

BackgroundIn esophageal adenocarcinoma (EAC), concordance and prognostic significance of human epidermal growth factor 2 (HER-2) protein overexpression and gene amplification are equivocal, which led us to reevaluate this by immunohistochemistry (IHC) and in situ hybridization.MethodsOne hundred and fifty-four patients were included in a tissue micro array (TMA). HER-2 gene amplification was assessed by fluorescence and silver-enhanced in situ hybridization (FISH and SISH) and expression with the HercepTest™.ResultsHER-2 was amplified in 16% by SISH and 18% by FISH. HER-2 positivity (IHC 3+ or 2+ with ISH+) was seen in 12% and overexpression (IHC 2+/3+) in 14%. Concordance was 92% between SISH/IHC, 90% between FISH/IHC and 95% between SISH/FISH. All IHC 3+ cases were amplified by SISH and in 93% by FISH. Of the IHC 2+cases, this was 33% (SISH) and 50% (FISH). Of the IHC 1+ cases, still 6% (SISH) and 8% (FISH) showed amplification. HER-2 positivity, overexpression and amplification were all associated with poor cancer-specific survival, in univariate analysis. Furthermore, HER-2 positivity and amplification (SISH) were independently associated with poor survival (hazard ratio, HR 6.343; 95% CI 1.218–36.234; P = 0.029 and HR 3.231; 95% CI 1.092–9.563; P = 0.034).ConclusionHER-2 positivity and gene amplification are fairly frequent and independently associated with poor survival.     

Prognostic significance of laminin in adenocarcinoma of the lung

The distribution of laminin in tumor-associated basement membrane was immunohistochemically investigated in 115 cases of adenocarcinoma of the lung. The distribution of laminin was classified into continuous and discontinuous staining patterns. The incidence of the discontinuous pattern was less in early-stage disease than that in advanced stages (P less than 0.01). In patients with stage I, the incidence of discontinuous patterns was greater in short-term survivors than in long-term survivors (P less than 0.05). By contrast, in patients with stage III, the discontinuous pattern of laminin was frequently seen in both long-term survivors and short-term survivors, with no difference between the two groups. These data suggest that the discontinuous pattern of laminin in tumor-associated basement membrane reflects the spread and dissemination of tumor, hence a close relationship to the prognosis.     

Matrigel: basement membrane matrix with biological activity

The basement membrane extracellular matrix contacts epithelial, endothelial, fat and smooth muscle cells. Because this extracellular matrix is so thin, it had been hard to study its composition, structure, and function. An extract of a tumor was found to contain all of the components present in basement and to be very biologically active. This extract, termed Matrigel, Cultrex, or EHS matrix, promotes cell differentiation, and is used to measure the invasive activity of tumor cells. In vivo, it is used for measuring angiogenic inhibitors and stimulators, to improve graft survival, repair damaged tissues, and increase tumor growth.     

Tumour necrosis factor in man: clinical and biological observations

Eighteen patients with advanced cancer have been treated intravenously with human recombinant tumour necrosis factor (rhTNF). The drug produced febrile reactions at all doses although these were preventable by steroids and indomethacin. Doses at or above 9 x 10(5) units (400 micrograms)m-2 were associated with hypotension, abnormal liver enzymes, leucopenia and mild renal impairment in a substantial proportion of patients. RhTNF was cleared from plasma with a half life of approximately 20 minutes but non-linear pharmacokinetics lymphoma, improvements in their tumours were recorded. RhTNF was noted to produce rapid increases in serum C-reactive protein concentrations. Endogenous TNF levels were not found to be elevated in 72 cancer patients. TNF deserves further therapeutic evaluation and these observations support its biological importance as an endogenous pyrogen, mediator of acute phase protein responses, and a mediator of endotoxic shock.     

Tumour microenvironment: laminin 332 in squamous-cell carcinoma

Basement membranes can be a barrier to tumour growth, but basement membrane molecules, including laminins, are also important autocrine factors produced by cancers to promote tumorigenesis. Many studies have shown the importance of laminin 332 (previously known as laminin 5) in this process, especially in squamous cell carcinoma. Through interactions with several cell-surface receptors (including alpha6beta4 and alpha3beta1 integrins, epidermal growth factor receptor and syndecan 1) and other basement membrane components (including type VII collagen), laminin 332 drives tumorigenesis through phosphatidylinositol-3 kinase (PI3K) and RAC1 activation, promoting tumour invasion and cell survival. The extracellular interactions of laminin 332 appear amenable to antibody-mediated therapies.     

层粘连蛋白在鼻咽癌中的表达及临床意义

目的探讨鼻咽癌中癌细胞及癌周基底膜层粘连蛋白(laminin,LN)的表达情况及临床意义.方法应用免疫组化S-P法对66例鼻咽癌组织蜡块进行层粘连蛋白检测.结果癌细胞LN阳性表达率为45.5%(30/66),癌周基底膜LN阳性表达率为36.4%(24/66);癌细胞LN表达与鼻咽癌T分期相关,与预后呈负相关,而癌周基底膜LN表达与淋巴结转移呈负相关;癌细胞LN阴性癌周基底膜LN阳性病例预后最好.结论层粘连蛋白的表达与鼻咽癌细胞的浸润、淋巴结转移有关,联合监测癌细胞及癌周基底膜LN的表达情况有助于判断鼻咽癌的预后.     

Basement membrane laminin and type IV collagen in endometrial adenocarcinoma: relation to differentiation and treatment

Changes in basement membrane (BM) structure were studied in functioning and hyperplastic endometrium, in adenocarcinomas with various degrees of differentiation and in progesterone-treated adenocarcinomas using electron microscopy and immunohistochemical staining with antibodies against human type IV collagen and laminin. These BM components were distinctly visualized as narrow, continuous bands beneath the epithelium and around the endometrial glands in functioning, atrophic and hyperplastic endometrium. In well-differentiated endometrial carcinomas there was mostly a continuous BM, though occasional disruptions were seen. The undifferentiated tumors, on the other hand, were characterized by the absence of a continuous BM structure, although irregular patches of BM material were found within the neoplasm. Hormonal treatment caused the reappearance of the BM structures. According to these results, the visualization of the BMs in the endometrium not only increases our understanding of tumor behavior, but can also be used as an aid for the classification and treatment of endometrial neoplasms.     

c-Met activation in lung adenocarcinoma tissues: an immunohistochemical analysis

c-Met is often overexpressed in non-small cell lung cancer, but it remains unsolved whether its overexpression leads to its activation. We used an antibody specific to phospho-c-Met (Tyr1235) to investigate c-Met activation immunohistochemically in 130 surgically resected lung adenocarcinomas. The expression of c-Met and hepatocyte growth factor (HGF) was also investigated. Phospho-c-Met was positive in 21.5% (28/130) of cases. c-Met was positive in 74.6% of cases (97/130) and was expressed at high levels in 36.1% of cases (47/130). HGF was expressed at high levels in 31.5% of cases (41/130). Phospho-c-Met was correlated with high levels of HGF (P =0.0010) and high levels c-Met expression (P = 0.0303), but it was also found to be positive in 12 cases with little to no HGF expression. Phospho-c-Met expression was significantly associated with tumor differentiation (P = 0.0023) and papillary histology (P = 0.0011), but not with pathological stage, lymph node metastasis or survival. High levels of c-Met and HGF were also associated with papillary histology (P = 0.0056 and P = 0.0396, respectively), but not with tumor differentiation. Phospho-c-Met was correlated with phospho-Akt (P = 0.0381), but not with phospho-Erk or phospho-Stat3. Phospho-Akt expression was marginally correlated with the expression of phospho-epidermal growth factor receptor (EGFR) (P = 0.0533) and, importantly, it was strongly correlated with the expression of either phospho-c-Met or phospho-EGFR (P = 0.0013). The data suggest that in lung adenocarcinoma tissue, c-Met activation may take place either ligand-dependently or ligand-independently via c-Met overexpression. c-Met activation may play special roles in the papillary subtype and in well differentiated lung adenocarcinomas.     

Clinicopathological and immunohistochemical study of 39 cases of Adenomatoid Odontogenic Tumour: a multicentric study

Adenomatoid Odontogenic Tumour (AOT) is a relatively uncommon odontogenic lesion and few studies describing its cytokeratin profile have been reported in the English-language literature. Thirty-nine cases of AOT from three Oral Diagnosis services (Brazil, Mexico and Guatemala) were studied, considering their clinical, radiographic, and histological features and immunohistochemical expression of cytokeratins (AE1/AE3, 34betaE12, CK1, CK5, CK6, CK7, CK8, CK10, CK13, CK14, CK16, CK18, and CK19), vimentin and Ki-67. Sixty five percent of cases affected women, anterior maxilla was the preferred site and radiographically most cases showed unilocular radiolucency with well defined sclerotic borders. Calcifying epithelial odontogenic tumour (CEOT)-like areas were found in 36 out of 39 cases, and 10 cases showed positivity for Congo red in polarized light. All cases were positive for AE1/AE3, 34betaE12, CK5, CK14 and CK19. CEOT-like areas were negative for CK 19. Vimentin was also expressed in 27 cases and this profile may indicate the existence of a variable phenotype in certain areas of the tumour. There were no recurrences after surgical treatment, and this can be related to the low proliferative activity observed in all cases with Ki-67 marker.     

Prognostic significance of sirtuin 2 protein nuclear localization in glioma: an immunohistochemical study

The sirtuin 2 (SIRT2) protein is a member of the sirtuin family and homologous to Sir2 (silent information regulator?2) of Saccharomyces cerevisiae. To assess the pathobiological significance of SIRT2 protein expression and/or subcellular localization in human glioma, we examined SIRT2 protein expression in human gliomas using a polyclonal anti-SIRT2 antibody and immunohistochemistry. In this study, samples from 23 patients with glioblastoma (GB, grade IV), 8 patients with diffuse astrocytoma (DA, grade II) and 5 healthy individuals were examined. We established a SIRT2 labeling index (SIRT2-LI) that represents the percentage of cells with SIRT2 localized to the nucleus. The mean SIRT2-LI was 65.8±18.6 in GB samples, 41.2±22.8 in DA samples, and 28.6±12.3 in normal control samples. The SIRT2-LI of GB samples was significantly higher than that of normal control samples (P<0.01, Mann-Whitney's U-test) and that of DA samples (P<0.05). Moreover, the SIRT2-LI was positively correlated with malignant progression. Specifically, samples from patients with GB were divided into two groups, low SIRT2-LI (<60%) and high SIRT2-LI (≥60%), and the patients with low SIRT2-LI samples survived significantly longer than patients with high SIRT2-LI samples (P<0.05, Kaplan-Meier method and log-rank test). In conclusion, SIRT2-LI was indicative of glioma malignancy, and it may be predictive of GB patient survival.     

Endometrioid adenocarcinoma of the prostate: A clinicopathologic and immunohistochemical study

On retrospective review of the tumor registry files between 1979 and 1992 at the North Iowa Medical Center, six cases of endometrioid adenocarcinoma of the prostate were identified among 1582 cases of prostatic carcinoma. Along with long-term clinicopathologic follow-up, immunohistochemical studies of the prostatic tumor tissues were performed. All six cases of endometrioid carcinoma, together with control cases of benign prostatic hypertrophy (BPH) and ordinary adenocarcinoma of the prostate had unequivocal diffuse positive staining for PSA and similar reactivity to ER-D5 and PS2. Thus, endometrioid carcinoma is most likely derived from the prostate or prostatic urethral duct rather than the utricle. However, due to its unusual initial clinical manifestations, biological behavior, and distinctive histomorphology, the term “endometrioid adenocarcinoma of the prostate” is worth preserving. © Wiley-Liss, Inc.     

Prognostic significance of heat-shock protein-27 in node-positive breast carcinoma: an immunohistochemical study

Immunostaining for heat-shock protein-27 (HSP-27) was performed on formalin fixed-paraffin embedded sections of 890 node-positive breast carcinomas resected between 1980 and 1986. The follow-up ranged from 2.5 to 10.5 years. A polyclonal antibody (Hu27, dilution: 1/200) was used. A positive cytoplasmic staining was obtained in 383 cases (43%). No difference in distant metastasis-free survival (DMFS) or overall survival (OS) was noted between cases with positive or negative immunostaining. This study suggests that HSP-27 expression is not predictive of the outcome in node-positive breast cancer.     

骨桥蛋白在子宫内膜样腺癌组织中的表达及其临床意义

目的:探讨骨桥蛋白(osteopontin,OPN)在子宫内膜样腺癌组织中的表达及与子宫内膜样腺癌临床病理特征的关系,探讨OPN对判断子宫内膜样腺癌患者预后的意义.方法:采用免疫组化方法(Envision法)测定OPN在46例子宫内膜样腺癌组织、16例正常子宫内膜组织中的表达.结果:OPN在子宫内膜样腺癌及正常子宫内膜组织中都有表达,在子宫内膜样腺癌组织中表达阳性率为86.96%,显著高于正常增殖期及分泌期子宫内膜组织,差异显著(P<0.05).在子宫内膜样腺癌中的表达同其细胞分化有关,低分化者高于中分化,高分化和中分化无明显差异,OPN阳性表达与患者年龄及临床病理分期无关.OPN表达阳性患者比阴性患者生存期缩短.结论:OPN对子宫内膜样腺癌的发生、发展起重要作用,OPN阳性表达是子宫内膜样腺癌患者负性预后因子.     

Mathematical evaluation of prognostic significance of clinico-morphological and immunohistochemical features of endometrioid adenocarcinoma

Complex examination was given to 76 patients with endometrioid adenocarcinoma and immunohistochemical parameters of estrogen and progesterone receptors, proliferative index (Ki-67), HER2 oncoprotein and clinico-morphological characteristics were entered into Excel database. Five-year relapse-free survival, development of regional metastases and relapse were used to work out three functional mathematical models. Those were employed to investigate endometrial tumorigenesis. A minimal set of the most advanced criteria of prognosis and assessment of tumor course served as tools for practical evaluation on the basis of clinico-morphological parameters, relapse, menopause duration, Ki-67 index and expression of PR and HER2.     

黏蛋白1在肺腺癌中的表达及临床意义

目的:探讨MUC1单抗4G10在肺腺癌中的染色情况及临床意义,为开发新的肺腺癌肿瘤免疫治疗方法提供理论依据.方法:以4G10作为一抗,C595作为对照,应用免疫组织化学方法检测342例肺腺癌和345例鳞癌中MUC1蛋白的表达情况.结果:肺腺癌组织中4G10染色多呈强阳性、弥漫性(2+~3+),阳性率为90.64%(310/342),明显高于C595的80.41%(275/342),而肺鳞癌组织中的阳性率为11.59%(40/345)(P<0.000 1),则低于C595的13.62%(47/345),且染色多呈阴性或弱阳性(0~1+)(P<0.000 1).342例肺腺癌中4G10的阳性率及染色强度与患者性别、年龄和有无吸烟史之间均不相关(P1=0.073 9,P2=0.160 3;P1=0.935 8,P2=0.936 6;P1=0.369 5,P2=0.618 4),但随着肿瘤恶性程度的增加、临床分期的递进及淋巴结的转移,4G10阳性率与染色强度增加,均分别呈现正相关趋势(P1=0.000 9,P2=0.000 3;P1=0.052 7,P2=0.039;P1=0.106 7,P2=0.037 4).结论:MUC1的异常表达与肺腺癌发生发展、侵袭、转移密切相关,可作为肺腺癌临床诊断的参考指标,对肺腺癌的恶性程度及预后判断有重要参考价值,并在肺腺癌的肿瘤免疫治疗中有望成为新的潜在靶点,发挥重要作用.     

子宫内膜样腺癌组织Maspin基因表达及其临床意义的研究

目的:探讨子宫内膜样腺癌组织Maspin基因的表达及其意义。方法:收集子宫内膜样腺癌标本35例,子宫内膜不典型增生10例,子宫肌瘤15例。应用免疫组化技术检测Maspin基因的表达。采用χ2检验对实验数据进行统计学分析。结果:Maspin基因在子宫肌瘤组织均为阴性表达,10例子宫内膜不典型增生组织中阳性表达2例(20.0%),35例子宫内膜样腺癌组织中阳性表达15例(42.85%),3组比较差异有统计学意义,P<0.01。子宫内膜样腺癌组与子宫肌瘤组比较差异有统计学意义,P<0.05。子宫内膜样腺癌Ⅲ期组织Maspin基因的阳性表达率为60.0%(6/10),高于Ⅰ期组织的36.0%(9/25);子宫内膜样腺癌组织中有淋巴结转移者Maspin基因的阳性表达率为100.0%(1/1),高于无淋巴结转移者的41.17%(14/34);但各组比较差异均无统计学意义,P均>0.05。结论:Maspin基因的表达与子宫内膜样腺癌的发生和发展可能有一定的关联。     

Napsin A在肺腺癌中的表达及临床意义

目的探讨Napsin A对肺腺癌的诊断价值及与肺腺癌分化程度、临床病期和淋巴结转移的关系。方法采用SP免疫组织化学方法检测47例肺腺癌患者的肺癌组织中Napsin A的表达,并与癌旁正常肺组织、46例其他组织学类型的肺癌组织和19例良性肿瘤组织对比。结果肺腺癌组Napsin A表达阳性率87．2％,显著高于非肺腺癌组4．3％（x^2=64．249,P〈0．01）和良性肿瘤组21．1％（x^2=27．317,P〈0．01）,但低于正常肺组织组100％（P〈0．05）;高分化、中分化和低分化肺腺癌组织中Napsin A表达阳性率分别为100％（20／20）、86．7％（13／15）和66．7％（8／12）,三者的阳性率具有显著性差异（x^2=7．489,P〈0．05）;Ⅰ～Ⅱ期腺癌组NapsinA表达阳性率为100％（24／24）,明显高于Ⅲ～Ⅳ期腺癌组73．9％（17／23）,P〈0．01;有淋巴结转移的肺腺癌组织Napsin A表达阳性率为72．7％（16／22）,明显低于无淋巴结转移者100％（25／25）,P〈0．05。结论Napsin A可以作为诊断肺腺癌的特异性肿瘤标记物,是判断肺腺癌恶性程度、临床病期及有无淋巴结转移的重要指标。     

胰腺癌组织增殖细胞核抗原的测定及其临床意义

目的　研究胰腺癌组织中增殖细胞核抗原 (PCNA)的表达与临床生物学行为之间的关系。方法　应用免疫组织化学ABC法对 39例存档胰腺癌标本和 8例慢性胰腺炎标本进行PCNA的定量分析。结果　 39例胰腺癌组织中PCNA增殖指数 (LI)为 2 7 5 4± 16 42 ,而 8例胰腺炎组织中未发现有PCNA的阳性表达 ,PCAN增殖指数与患者的年龄、性别及肿瘤的部位无关 (P >0 0 5 ) ,而与肿瘤的大小、组织学分级、临床分期及淋巴结转移密切相关。结论　PCNA是反映胰腺癌生物学行为和预后的重要指标 ,高表达提示肿瘤的恶性程度高 ,预后不良。