New attempt of preoperative differential diagnosis of thyroid neoplasms by telomerase activity measurement

Telomerase activity (TA) has been shown highly expressed in various solid malignant neoplasms, but only rarely in benign tumor or normal tissues. Most reports examined TA by the qualitative method, telomeric repeat amplification protocol (TRAP) assay. We examined TA in tissues of thyroid neoplasm by quantitative method to establish whether TA was a useful marker for preoperative differential diagnosis of thyroid tumors. TA was measured by the quantitative method, TRAP assay, fluorescence based TRAP method in 32 frozen tissues of thyroid tumors (17 malignant, 15 benign). Cut-off values in TA were 0 unit and 9 units from mean +/- 2SD of TA in benign thyroid tumors. Mean (SD) TA levels in benign thyroid tumors and thyroid carcinomas were 2.06 (3.58) units and 30.5 (38.2), respectively. Mean TA of carcinomas was significantly higher than that of benign disease in thyroid tumors (p=0.0092). The sensitivity of the malignancy was 64.7% (cut-off <0) (p=0.162), 52.9% (cut-off <9) (p=0.0048). TA in thyroid carcinoma was significantly correlated with UICC stage (p=0.029), and slightly correlated with tumor size, pN and M. Positive rate of TA in microfollicular adenoma was slightly higher than that in macrofollicular adenoma. Conclusively, quantitative TA might be a useful marker for differential diagnosis between benign and malignant thyroid tumors.     

A nucleolar antigen found in a broad range of human malignant tumor specimens.

With rabbit antibodies to nuclear 0.01 M Tris-HCl, pH 8, extract or "nucleolar preparations" of human HeLa S3 cells and fluorescein-labeled goat anti-rabbit antibodies, bright nucleolar immunofluorescence was observed in 61 or 63 human adenocarcinomas, squamous cell carcinomas, sarcomas, hematological neoplasms, and other malignant tumors. With these antibodies, nucleolar immunofluorescence was not found in 23 normal tissue specimens, 10 benign adenomas and hyperplastic tissues, and 8 specimens of inflammatory diseases. In the nontumorous tissues examined, positive nucelolar fluorescence was found in a few sections of a gastric ulcer and chronic ulcerative colitis which have been known propensities for malignant change; these areas may have been undergoing focal malignant changes.     

Changing expression of ABH blood group and cryptic T-antigens of noninvasive and superficially invasive papillary transitional cell carcinoma of the bladder from initial occurrence to malignant progression

Thirteen patients who developed malignant progression after frequent recurrence of noninvasive or superficially invasive (Ta or T1) papillary transitional cell carcinoma of the bladder were studied for expression of ABH-antigens in tumor tissues throughout their clinical courses and cryptic Thomsen-Friedenreich antigen (T-Ag) expression in the tumor tissues was examined simultaneously in nine of them. Five patients who experienced recurrent bladder tumors for more than 5 years without any malignant progression were served as control. ABH-antigens in initial tumors were negative in only two of 13 patients developing malignant progression and in two of five controls. Cryptic T-Ag was positive in all patients examined. Recurrent tumors revealed eliminated or decreased expression of ABH-antigens and cryptic T-Ag before malignant progression in, respectively, ten of 11 and six of nine patients with antigen-positive initial tumors. In contrast, recurrent tumor of controls with antigen-positive initial tumors showed neither elimination nor decrease in expression of antigens throughout their clinical courses.     

Evaluation of galectin-3 expression by sarcomas,pseudosarcomatous and benign lesions of the soft tissues. Preliminary results of an immunohistochemical study

Galectin-3 is an endogenous galactose-binding protein that is expressed in several normal and neoplastic tissues and is thought to play a role in a variety of biological processes. In this study we have examined the immunohistochemical expression pattern of galectin-3 in the most representative categories of soft tissue tumors consisting of 162 patients' specimens. Lesions were classified according to histogenetic criteria into 13 major categories. Overall, there were 18 fibrous tumors (13 benign, 4 intermediate and 1 malignant), 21 fibrohistiocytic tumors (5 benign, 11 intermediate and 5 malignant), 22 lipomatous tumors (14 benign and 8 malignant), 20 smooth muscle tumors (12 benign, 5 intermediate and 3 malignant), 2 skeletal muscle tumors (2 malignant), 19 vascular tumors (9 benign and 10 malignant), 6 perivascular tumors (5 benign and 1 malignant), 7 synovial tumors (4 benign and 3 malignant), 3 benign mesothelial tumors, 27 neural tumors (25 benign and 2 malignant), 7 cartilaginous and osseous tumors (4 benign and 3 malignant), 8 miscellaneous tumors and 2 high grade unclassified sarcomas. Galectin-3 was constantly expressed by almost all the major categories of benign, pseudosarcomatous and malignant soft tissue tumors. At this time no data are available in the literature about the expression of galectin-3 distribution in a wide range of soft tissue tumors. In the present work we discuss the significance and the possible usefulness of such findings.     

Extracorporeal photodynamic image detection of mouse osteosarcoma in soft tissues utilizing fluorovisualization effect of acridine orange

Various imaging methods have been employed for the extracorporeal detection of malignant tumors in the human body, such as scintigraphy and PET; however, none is sufficiently accurate and all are also very expensive. To resolve these issues, we attempted to develop a new imaging technique of photodynamic diagnosis (PDD) with acridine orange (AO). AO has the ability to rapidly and specifically accumulate in malignant tumors and emit brilliant green fluorescence after blue light excitation. In this study, we investigated the feasibility of PDD utilizing the fluorovisualization effect of AO, for the extracorporeal detection of mouse osteosarcoma inoculated into the soft tissues. At 2 h after intravenous administration of 0.1, 0.2, 0.5, 1.0, 2.0 and 5.0 mg/kg AO, the tumor and the surrounding normal tissues were illuminated by blue light. The visual fluorescence contrast and ratio (X) of the difference in fluorescence intensity between the tumor and the surrounding normal tissues were evaluated using a high-resolution digital camera equipped with an absorption filter. In addition, the fluorescence contrast was also detected sequentially at 0.5, 1, 2, 3, 6 and 12 h after intravenous administration of AO at 1.0 mg/kg. The results revealed that the optimal condition for clear detection of the tumor was evaluation 2 h after intravenous injection of AO at 0.1 mg/kg, because it provided the best visual contrast on the digital images, and the fluorescence intensity as well as the value of X were higher as compared to the values under other conditions of dose and timing. Based on the results of an acute toxicity study of AO, the estimated LD50 of this substance following intravenous administration was 27.30 mg/kg. In conclusion, we believe that PDD using AO administered intravenously may be feasible for the detection of human musculoskeletal sarcomas in the soft tissues at extremities, and this technique might be a less invasive, less expensive, quicker and more accurate imaging modality than other previously reported imaging methods for this purpose.     

Diagnostic targeting of colon cancer using a novel fluorescent somatostatin conjugate in a mouse xenograft model

Colorectal carcinoma is one of the more prevalent, highly malignant human tumors, occurring in about 7% of the population. However, if diagnosed and treated in its early stages, colon cancer is curable. In our study, we used a mouse xenograft model to investigate the capability of a fluorescent conjugate of a novel synthetic somatostatin (SST) analog to improve detection of human colorectal tumors that are characterized by over-expressed SST receptors. Human HT-29 colon carcinomas were induced in nude mice. After administration of the fluorescent SST conjugate, in vivo low- and high-magnification fluorescence microscopy, as well as high-resolution spectrally resolved imaging were performed, and the time-dependent biodistribution was determined quantitatively (using fiber-optic spectroscopy). Administration of the conjugate (at concentrations of 6 mg/kg body weight) enabled targeting small (1-5 mm diameter) tumors with high sensitivity and selectivity. Toxicity studies at dosages up to 1,000 mg/kg body weight did not reveal any drug related abnormalities. In conclusion, the SST conjugate significantly enhanced the detection of HT-29 colon tumors by fluorescence imaging because of a 5- to 8-fold increase in the contrast between malignant and normal tissues.     

常见恶性肿瘤端粒酶活性检测

目的 探讨端粒酶活性检测在常见恶性肿瘤诊断中的作用。方法 采用改良的银染端粒重复序列扩增方法,对283例恶性肿瘤、61例良性肿瘤和42例癌旁组织进行端粒酶活性检测。结果 283例恶性肿瘤中,264例检测到端粒酶活性,阳性率为93．3％;61例良性肿瘤中,4例检测到端粒酶活性,阳性率为6．6％;42例癌旁组织中,11例检查到端粒酶活性,阳性率为26．2％。结论 端粒酶的激活与恶性肿瘤的发生发展密切相关。端粒酶可以作为一种有效的恶性肿瘤标记物用于恶性肿瘤的诊断。     

Le^y抗原在卵巢上皮性肿瘤中的表达及意义

目的：探讨卵巢癌组织Le^y抗原的表达及其临床意义。方法：采用免疫组织化学SP法检测恶性、交界性、良性卵巢上皮肿瘤及正常卵巢组织中Le^y抗原的表达，并分析其与卵巢癌生物学特性之间的关系。结果：Le^y抗原在恶性卵巢上皮性癌中的阳性表达率为75．47％（40／53），明显高于交界性卵巢上皮性肿瘤（47．06％）及良性卵巢上皮性肿瘤（42．86％）（P均〈0．05）。正常卵巢组织中未检出Le^y抗原的表达。晚期卵巢上皮性癌的Le^y抗原的阳性表达率为84．21％，明显高于早期卵巢上皮性癌（53．33％），（P〈0.05）。结论：Le^y抗原与卵巢上皮性癌的发生、发展相关。Le^y抗原的表达可作为反映卵巢癌恶性潜能的一项新的指标。     

Distribution of acid stable trypsin inhibitor immunoreactivity in normal and malignant human tissues

The distribution and localization of acid stable trypsin inhibitor (ASTI) in normal and malignant human tissues from various organs were examined using immunohistochemical techniques that used goat antibody raised against highly purified ASTI from human urine. Tissues were assessed as positive only when they were stained by both the biotin-avidin-peroxidase complex system and biotin-streptavidin-beta-galactosidase complex system, and the staining was abolished by absorption with purified ASTI. Under normal conditions, ASTI immunoreactivity was observed in only a few organs. Positive tissues for ASTI immunoreactivity included the kidney proximal tubules, glial cells of the cerebrum, fibrillar structures of the lamina propria of the stomach and colon, and bronchial epithelial cells. No ASTI immunoreactivity was observed in the cardiovascular system, reproductive system, or other tissues examined. As is not the case for normal tissues, ASTI immunoreactivity was found to be widely distributed in malignant tumors. Staining was observed in the extracellular space, i.e., in the stroma of the tumor and in connective tissues around the tumor invasion, whereas no ASTI immunoreactivity was detected in the malignant cells. Considering the identity of the first 36 NH2-terminal residues of ASTI purified from plasma or urine with a recently reported endothelial cell growth factor, the present findings suggest that ASTI could play an important role, not limited to its function as a protease inhibitor, in the invasive growth of malignant neoplasms.     

妇科恶性肿瘤组织诱导血管形成与临床预后因素的相关性

目的探讨妇科恶性肿瘤组织诱导兔角膜血管形成分级可否作为判断患者预后的一项监测指标,并对妇科三种恶性肿瘤之间的生物学行为进行评价。方法分析１１例卵巢恶性肿瘤,１０例乳腺癌,９例子宫内膜癌诱导兔角膜血管形成分级与临床预后因素之间的关系,并对三种恶性肿瘤诱导兔角膜血管生成活性进行比较。结果Ⅱ级血管形成在临床Ⅱ～Ⅳ期,淋巴结阳性或有转移灶的病例明显高于临床Ⅰ期,淋巴结阴性或无转移灶的病例,差异有极显著性（Ｐ＜０．０１）。血管形成分级与组织学分级及肿瘤直径之间差异无显著性（Ｐ＞０．０５）。血管形成活性卵巢恶性肿瘤为“＋＋＋”,乳腺癌和子宫内膜癌分别为“＋＋”。结论瘤组织诱导兔角膜血管形成分级可作为判断肿瘤患者预后指标之一。血管形成活性在这三种恶性肿瘤排列顺序与他们的生物学行为相一致,其预后卵巢恶性肿瘤最差。     

Overexpression of the tumor-suppressor gene p53 in human ovarian tumor-tissues and its correlation with clinical stage

An extensive series of histological sections from various types of benign, borderline, and malignant human ovarian tumors were examined for expression of the p53 protein by immunohistochemical staining, using a new anti-p53 mouse monoclonal antibody. Positive staining for p53 was detected in 34% of all malignant ovarian cancer tissues. A high rate of positivity was observed in serous cystadenocarcinoma (59.7%). None of the borderline or benign tumors showed any reaction. No relation was observed between clinical stage, and the frequency of p53 positivity. Mutation of the p53 gene with overexpression of the mutant protein appears to be a specific genetic change in human ovarian cancer.     

Quick diagnosis of malignant melanoma with the touch-fluorescence method during operation

Nine cases of primary melanotic melanoma, three cases of metastatic amelanotic melanoma, and 26 cases of pigmented and unpigmented tumors other than melanoma were examined with the touch-fluorescence method using preparations from the cut surface of the lesions. Fluorescent melanoma cells were easily detected with a fluorescence microscope in all the cases of malignant melanoma whether the melanoma was melanotic or amelanotic. The fluorescent melanoma cells could be divided into three types by configuration: round, spindle-shaped, and pleomorphic. The main cell type of superficial spreading melanoma was round and that of nodular melanoma and acral lentiginous melanoma was chiefly pleomorphic. Fluorescent tumor cells were not seen in pigmented and unpigmented tumors other than melanoma, except in pigmented basal cell epithelioma; this fact made it possible to apply this method routinely for quick diagnosis of malignant melanoma during operation.     

Dual FISH analysis of benign and malignant tumors of the salivary glands and paranasal sinuses

To date, the underlying genomic changes in benign and malignant tumors of salivary-gland and paranasal-sinus origin are poorly understood. This is due in part to the low incidence of these tumors and the enormous histological variety of tumors within this head and neck region. We examined 58 of these tumors (14 adenoid cystic carcinomas, 9 adenocarcinomas, 5 cylindrical carcinomas, 11 pleomorphic adenomas, and 19 inverted papillomas) by dual fluorescence in situ hybridization (FISH) with centromere-specific probes on six chromosomes (3, 7, 9, 11, 17, and 18) for numerical changes. In adenoid cystic carcinomas, monosomy of chromosome 17 and polysomy of chromosomes 3, 9 and 11 were most frequently encountered. In adenocarcinomas, monosomy of chromosome 17 and polysomy of chromosomes 7 and 11 were most frequent. In cylindrical cell carcinomas, polysomy of chromosomes 7, 9, 11 and 17 was present in the majority of tumors. Disomy is rare, even in benign tumors. Polysomy is more frequent in malignant tumors than in benign. Tetrasomy is found almost only in malignant tumors. In summary, the occurrence of polysomy might reflect a step towards malignancy in tumors of the salivary glands and paranasal mucosa. Polysomy of chromosome 11 could be defined as typical for all investigated histological types of malignant tumor in this region of the head and neck.     

Relationship between fibrinolysis of cultured cells and malignancy.

Cells cultured from various human and nonhuman malignant and normal tissues as well as mammalian cells transformed in vitro were examined for their ability to induce fibrinolysis. Generally, except for normal cells derived from lung or kidney, malignant cells had a greater ability to induce fibrinolysis than did their normal counterparts. A correlation existed between the abilities of the cells to induce fibrinolysis, grow in soft agar, and form tumors in immunosuppressed hosts.     

Optimal excitation-emission wavelengths for autofluorescence diagnosis of bladder tumors

Tissue autofluorescence depends on endogenous fluorophores in the tissue, which undergo a change associated with malignant transformation. This change can be detected as an alteration in the spectral profile and intensity of autofluorescence. Our purpose was to determine the optimal excitation and emission wavelengths for autofluorescence diagnosis of bladder cancer. A total of 52 bladder tissue specimens were obtained from 25 patients undergoing mucosal biopsies or surgical resections of bladder tumors. Light-induced autofluorescence measurements were performed to study the spectroscopic differences between normal and malignant bladder tissue. Fluorescence excitation wavelengths varying from 220 to 500 nm were used to induce tissue autofluorescence, and emission spectra were measured in the 280-700 nm range. These spectra were then combined to construct 2-dimensional fluorescence excitation-emission matrices (EEMs). Significant changes in fluorescence intensity of EEMs were observed between normal and tumor bladder tissues, the most marked differences being at the excitation wavelengths of 280 and 330 nm. The diagnostic algorithm based on the combination of the fluorescence peak intensity ratios of I(350)/I(470) at 280 nm excitation and I(390)/I(470) at 330 nm excitation yielded a sensitivity of 100% [95% confidence interval (CI) 0.95-1.0] and specificity of 100% (95% CI 0.90-1.0). The results of the present fluorescence EEM study demonstrate that autofluorescence spectroscopy can distinguish malignant from normal bladder tissue and that excitation wavelengths of 280 and 330 nm are the most significant for differentiation between normal and malignant bladder mucosae with a high degree of diagnostic accuracy.     

Special expression of Thy-1 in different malignant tumors

Objective:To investigate the expression status of Thy-1 in malignant cancerous tissues and to evaluate whetherThy-1 could be a potential tumor marker. Methods:Immunohistochemistry method was used to examine Thy-1 expressions in different malignant tumor tissues. We used a monoclonal antibody specific for Thy-1 and the indirect Catalysis Signal Amplification method. With the help of tissue microarray (TMA), we examined expression the status of Thy-1 in 1451 different types of malignant tumor tissues, 144 normal tissues and benign lesions. Results:All the malignant tumor cells were grouped as one group (malignant cells group) and normal or benign tumor tissue cells as another group (normal cells group). Among the entire 1451 malignant cases group, positive Thy-1 expression with diffuse and strong staining was observed in 734 (734/1451; 50.59%) cases. In the benign cases only 6 chronic cervicitis cases showed weak staining for Thy-1. All the normal tissue showed negative staining. One-Way ANVOA analysis showed F value between these two groups was 147.229 (P<0.0001). Conclusion:A significantly stronger expression of Thy-1 in malignant tumors was observed. Special overexpression of Thy-1 in malignant tumors suggests that Thy-1 might be a potential novel tumor marker with respect to cancer progression. Chronic cervicitis has some relationship with cervix carcinoma. When it develops into atypical hyperplasia, it will be a precancerous lesion for cervix carcinoma. In this research we found weak staining for Thy-1 in chronic cervicitis lesion, so Thy-1 may play a crucial role in carcinogenesis for cervix carcinoma. The research about the relationship between Thy-1 expressions in cancer cells and in precancerous lesion will provide some clues to understand the mechanism for carcinogenesis process.     

腮腺肿瘤病理与CT诊断分析

目的：探讨ＣＴ检查对腮腺疾病的诊断价值。方法：采用腮腺疾病术后病理检查材料,并结合术前ＣＴ检查结果对照方法进行回顾性分析。结果：病检恶性肿瘤６例,良性病变５例。ＣＴ检查为恶性肿瘤３例,３例可能为良性、４例良性肿瘤、１例炎性病变不除外早期癌。结论：腮腺ＣＴ扫描对肿瘤定位较明确,明显良性或恶性肿瘤者要结合组织密度和边缘情况确定。特殊病变ＣＴ诊断有困难者要考虑术中快速冰冻病理诊断。     

31P magnetic resonance spectroscopic profiles of neoplastic human breast tissues

Phosphorus-containing metabolites of human breast tissues from malignant, benign, and noninvolved breast parenchymal specimens were examined by using techniques of perchloric acid extraction and 31P magnetic resonance spectroscopy. Twenty-four separate resonances arising from the established phosphorylated metabolites of high-energy- and low-energy-phosphate intermediary metabolism were identified and quantitated. Subsequent to magnetic resonance spectroscopic analysis, the data from the three tissue groups were compared and contrasted on a statistical basis by using Scheffé simple and complex contrast procedures. Theories of tumor metabolism and biochemical interactions were invoked, including the tissue high-energy-/low-energy-phosphate modulus, the phosphomonoester/Pi ratio, and 10 other metabolic indices. The data demonstrated the ability of 31P magnetic resonance spectroscopy to differentiate among the three tissue groups. Both benign and malignant tumors demonstrated comparable Warburg effects. Phosphomonoester metabolism was shown to be altered in neoplastic tissues relative to the noninvolved tissues. Phosphocreatine was elevated in benign tumors. This elevation in phosphocreatine plus a parallel elevation in an uncharacterized phosphate resonating at a chemical shift of 3.66 delta permits the important differentiation between malignancy and benignancy in human breast disease. The tissue energy modulus indicated that benign tissue is relatively more aerobic than noninvolved tissue and significantly more aerobic than malignant tissue.