COX-2及survivin在涎腺多形性腺瘤中表达的定量研究

目的　探讨环氧合酶- 2 (COX- 2 )及生存素(survivin)在良、恶性涎腺多形性腺瘤中的表达及其与肿瘤发生发展的关系。方法　采用流式细胞技术检测5 0例良性、17例恶性涎腺多形性腺瘤组织中COX- 2与survivin的表达,并与10例正常腮腺组织进行对比分析。结果　良、恶性涎腺多形性腺瘤及正常腮腺组织COX- 2的阳性表达率分别为76 %、10 0 %、0 ,其荧光指数(FI)分别为1.79±0 .12、3.0 1±0 .4 0、0 .82±0 .0 5。survivin阳性表达率分别为5 6 %、10 0 %、0 ,FI分别为1.0 6±0 .5 9、1.85±0 .16、0 .5 6±0 .0 8。各组间COX- 2与survivin表达量有明显差异(P均<0 .0 1)。在17例恶性涎腺多形性腺瘤中COX- 2与survivin的协同表达率为10 0 %。结论　COX- 2与survivin基因与涎腺多形性腺瘤的发生及恶变关系密切。     

涎腺多形性腺瘤survivin蛋白的表达及意义

目的探讨survivin在涎腺多形性腺瘤发生发展中的作用。方法收集多形性腺瘤28例及恶性多形性腺瘤7例蜡块标本。免疫组化法测定survivin蛋白含量。结果survivin在正常涎腺组织中不表达,在28例多形性腺瘤中阳性表达8例（28.57%）,7例恶性多形性腺瘤中5例阳性（71.43%）。结论survivin在涎腺肿瘤有着不同程度的表达,survivin能够在一定程度上反映肿瘤的恶性程度及肿瘤的预后。     

血管内皮生长因子、增殖细胞核抗原在良恶性腮腺多形性腺瘤中的表达及意义

目的探讨腮腺多形性腺瘤组织中血管内皮生长因子(VEGF)、增殖细胞核抗原(PCNA)的表达和相关性及其在腮腺多形性腺瘤细胞增殖活性中的意义。方法采用免疫组织化学技术SP法,检测61例人腮腺多形性腺瘤组织和29例正常腮腺组织中PCNA和VEGF的表达。结果VEGF、PCNA在正常腮腺组织与良性腮腺多形性腺瘤组中均有显著差异(P均<0.05);良性组与恶性组间比较VEGF有显著差异(P<0.05),PCNA则有非常显著差异(P<0.01);在VEGF阳性表达病例中PCNA的表达随VEGF表达强度的升高而升高,二者呈显著正相关(P<0.01)。与正常腮腺组织比较,VEGF及PCNA在良恶性腮腺多形性腺瘤中均呈高表达,恶性腮腺多形性腺瘤与良性腮腺多形性腺瘤相比VEGF及PCNA的阳性表达率更高。结论 VEGF和PCNA的表达可以作为腮腺判断腮腺多形性腺瘤恶性程度和预后的参考指标。     

ras基因在涎腺多形性腺瘤中的表达及意义

应用免疫组织化学ＳＡＢＣ法，对５２例良性多形性腺瘤（ＢＰＡ）、１３例恶性多形性腺瘤（ＭＰＡ）、６例正常人（对照组）涎腺组织中的ｒａｓＰ蛋白进行检测。     

C—erbB—2P185蛋白在多形性腺瘤中的表达及意义

应用免疫组织化学ＳＡＢＣ法对５２ 例良性多形性腺瘤（ＢＰＡ）、１３ 例恶性多形性腺瘤（ＭＰＡ）患者及６ 例正常涎腺（对照组）者涎腺组织中的Ｃ－ｅｒｂＢ－２Ｐ１８５ 蛋白进行检测,结果：Ｃ－ｅｒｂＢ－２Ｐ１８５ 蛋白阳性表达率在对照组为０,ＢＰＡ组为６９．２３％ ,ＭＰＡ组为９２．３１％ ;ＢＰＡ组、ＭＰＡ组与对照组比较有极显著差异（Ｐ＜ ０．００１）,ＢＰＡ组与ＭＰＡ组之间亦有显著差异（Ｐ＜ ０．０１）。提示Ｃ－ｅｒｂＢ－２Ｐ１８５ 蛋白在涎腺多形性腺瘤的发生、发展过程中起重要作用。     

涎腺黏液表皮样癌组织中5-LOX、MVD的表达变化及意义

目的观察5-脂氧合酶（5-LOX）、微血管密度（MVD）在涎腺黏液表皮样癌（MEC）中的表达变化,并探讨其临床意义。方法采用免疫组化EliVision法检测40例涎腺MEC、20例多形性腺瘤、20例癌旁2 cm正常组织中的5-LOX、CD34（以此标记MVD）。结果涎腺MEC中5-LOX的阳性表达率为67.5%（27/40）、MVD为（24.825±9.685）条/HP,多形性腺瘤、癌旁正常组织分别为0（0/20）和（8.20±1.735）条/HP、5.0%（1/20）和（9.9±1.373）条/HP,前者与后两者的两个指标相比,P均〈0.05。5-LOX的表达与涎腺MEC的分化程度有关（P〈0.05）,MVD的表达与涎腺MEC的分化程度、淋巴结转移有关（P均〈0.01）。结论5-LOX、MVD在涎腺MEC组织中呈高表达,且与肿瘤分化程度、淋巴结转移有关,可以作为诊断涎腺MEC及判断其生物学行为的参考指标。     

p53和hTERTmRNA在涎腺恶性肿瘤中的表达及意义

涎腺黏液表皮样癌(MC)、腺样囊性癌(ACC)及多形性腺瘤恶性变(MPA)均为常见涎腺癌,我们采用原位杂交及免疫组织化学法检测了54例涎腺癌患者癌组织中hTERTm-RNA及p53蛋白的表达情况,现探讨其临床意义.     

涎腺肿瘤患者中p185蛋白和p16蛋白表达及临床意义

用免疫组化LSAB法检测维吾尔族患涎腺恶性肿瘤13例、涎腺多形性腺瘤11例及涎腺非肿瘤组织10例的p185蛋白及p16蛋白的表达及变化，探讨抑癌基因p16（表达产物为p16蛋白）、原癌基因C－erbB-2）表达产物为p185蛋白）在新疆维吾尔族涎腺肿瘤患中的异常表达与肿瘤病理生物学特征间关系及临床意义，为涎腺恶性肿瘤的有效防治提供科学实验依据，本研究得出：（1）免疫组化法检测p185及p16蛋白的表达，可对良、恶性病变从分子水平进行评估，并可作为早期诊断及临床治疗涎腺恶性肿瘤的分子生物学指标；（2）p185蛋白的过度表达可能与良性病变的恶性转化有关。     

涎腺多形性腺瘤253例临床分析

涎腺多形性腺瘤为多发性良性肿瘤，治疗不当可引起复发。本文对1983年～1998年我院收治的253例涎腺多形性腺瘤患者进行回顾性分析，并总结治疗体会。     

印片细胞学及DNA倍体分析对乳腺疾病的诊断价值

目的 探讨组织印片细胞学与DNA倍体分析对乳腺疾病良恶性的诊断价值.方法 通过组织印片细胞学及DNA倍体全自动图像分析仪分别对80例乳腺疾病的良恶性作出诊断,与常规石蜡切片病理诊断及免疫组化结果进行比较.结果 组织印片细胞学对乳腺疾病良恶性诊断的特异性为92.7%,敏感性72%,准确率86.25%;DNA倍体分析的特异性为100%,敏感性92%,准确率97.5%.结论 组织印片细胞学和DNA倍体分析对乳腺疾病良恶性的诊断具有较高的价值.     

Cytofluorimetric measurements on the DNA contents of tumors cells in human thyroid gland

Summary The relative DNA contents of thyroid cell nuclei were measured in surgically removed thyroid tissue of 50 patients by means of cytofluorimetry. Smears were prepared immediately after removal of the thyroid nodules according to the classical Feulgen technique. The fluorescence intensities were always compared with those of healthy thyroid tissue prepared in the same way. In each case samples were investigated by the usual histology. The observations indicate that differentiated carcinomas of thyroid gland, have an increased DNA content of nuclei, at about the tetraploid level. Among them the follicular carcinomas (11 cases) showed an even higher DNA content of about 250% of the diploid level. Frequency distribution of the cell pools studied revealed a widely scattered aneuploidization of the malignant tumor cells. The benign adenomas displayed only a moderate increase of nuclear DNA content reaching only about 130% of the diploid value. Among the 22 adenomas classified histologically as of benign character, two cases showed very highly increased and widely scattered DNA contents. These latter two cases might be in process of malignant transformation. DNA cytofluorimetry may contribute to a more safe differential diagnosis of the follicular neoplasia of the thyroid gland.     

Flow cytometry of radiation-induced tumors in rats

Hundred sixty female Wistar rats were total-body irradiated with 4 Gy gamma rays. Mammary gland tumors started to occur 8 months after irradiation, beside that also tumors of different sites appeared. By flow cytometry (FCM) 30 tumors were examined: mammary gland--22, skin--4, adrenal gland--2, liver--1, thymus--1. Eight tumors were characterized as malignant and 22 as benign. All benign and 6 malignant tumors were composed of diploid cells only. In 2 carcinomas together with diploid cells aneuploid cell lines were also found. DNA index (DI) of aneuploid cells in both carcinomas (1 mammary gland and 1 adrenal gland) indicated values of 1.66 and 1.68, respectively. Most cells of the benign and the malignant tumors occupied G1/0 (79-94%) phase of the cycle. The fraction of S (4.1-14.3%) and G2M (0.5-7.7%) cells was relatively small that suggests a low proliferative activity of radiation-induced tumors.     

DNA evaluation in growth hormone producing pituitary adenomas: flow cytometry versus single cell analysis

DNA patterns were analysed in 26 GH-producing pituitary adenomas by flow cytometry as well as by microspectrophotometry. Twelve tumours (46%) were diploid according to both methods, whereas 5 tumours (19%) showed aneuploid DNA patterns. Nine tumours were classified differently by the two methods: flow cytometry resulted in diploidy in 2 and aneuploidy in 7 patients, whereas microspectrophotometry showed diploidy in 5 tumours, tetraploidy in 3 and aneuploidy in 1. Methodological limitations may explain the discrepancy in the results obtained by the two methods. However, both the flow cytometry and the microspectrophotometry method show the presence of aneuploid DNA patterns in GH-producing pituitary adenomas despite their benign growth characteristics and the clinically benign course of the disease. This comparative study with two methods measuring DNA content, shows that depending on the criteria used for diploidy-aneuploidy, the frequency of aneuploidy will vary. In this material of 26 GH-producing adenomas, 46% were aneuploid according to flow cytometry and 23% according to microspectrophotometric. However, no correlation to tumour size or GH levels was found with either method when patients with aneuploid and diploid tumours were compared. Therefore, no clinical significance can so far be drawn from these results.     

DNA content analysis in thyroid neoplasms: diagnostic and prognostic interest

Thyroid nodules are frequent and sometimes they pose a diagnostic and prognostic problem. DNA ploidy study and cell cycle analysis could be of value in the distinction between benign tumors and malignant tumors. Formalin-fixed and paraffin-embedded tissues from 69 patients with different benign and neoplastic lesions were investigated. Nuclear DNA content in thyroid cells was measured after Feulgen staining using SAMBA 200 image analysis system. A diploid DNA stemline was revealed in 75% of histologically proven benign thyroid tumors (15/20) and aneuploidy was found in 57.2% of malignant tumors (28/49). There is a significant correlation between aneuploidy and extra-thyroid extension (p=0.007) and bilateral and/or mediastinal lymph node metastasis (p=0.02). In the majority of benign tumors (19/20), the proliferation index was lower than 3% (< or =3%) however, this index value was higher than 3% (>3%) in more than 83% of malignant tumors (41/49) (p<0.001). The S phase fraction analysis revealed that the threshold of 14% divide the near whole of benign and malignant tumors (p<0.001). Our findings show that in follicular lesions, proliferation index and S phase fraction study appears interesting and helpful in the distinction between benign and malignant tumors, and aneuploidy seems more interesting in prognosis evaluation of these tumors.     

DNA and S-phase representation in human growth hormone producing pituitary adenomas

The DNA contents of 33 pituitary adenomas from patients with acromegaly were analysed with flow-cytofluorometry. Degrees of ploidy and the proliferation rate, expressed as percentage of cells in S-phase, were determined. The aim was to compare these morphological and functional tumour properties with clinical and laboratory parameters to establish a possible relation and to further elucidate the characteristics of these tumours. In 15 tumours (45%) diploid DNA pattern were found, while 18 (55%) showed varying degrees of aneuploidy. The frequency of cells in S-phase showed wide variations and were equally distributed in diploid and aneuploid tumours. Duration of symptoms, age at diagnosis, preoperative growth hormone (GH)- and prolactin (Prl)-levels, tumour size and grade of invasive tumour growth as determined by radiological estimations, did not correlate to ploidy or grade of proliferation. The lack of correlation between DNA pattern and proliferation rate in relation to clinical, laboratory and radiological parameters in tumours causing acromegaly contrasts to the documented relation between the degree of ploidy, cells in proliferation and grade of malignancy reported in tumours of other sites. The 55% aneuploid GH producing tumours indicate a certain malignant transformation. The high frequency of cells in S-phase in several GH secreting tumours completes the malignant morphological and functional cell properties. The benign character of tumours causing acromegaly is therefore in contrast to these findings. The lack of clinical significance of the DNA pattern and the frequency of cells in proliferation in GH producing tumours and the benign character despite malignant cell properties in most of these tumours are difficult to explain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Malignant solid and pseudopapillary tumor of the pancreas--clinicohistological, immunohistochemical, and flow cytometric evaluation

BACKGROUND/AIMS: Solid and pseudopapillary tumor of the pancreas is a benign and low malignant potential tumor. Prognosis is good after surgical resection but its malignant potential is usually defined after metastasis. We compared benign and malignant cases with clinicopathological, immunohistochemical and DNA flow cytometric studies. METHODOLOGY: From January 1991 to July 2004, seven patients were found to have solid and pseudopapillary tumor of the pancreas at Taipei Veterans General Hospital. The paraffin sections were reevaluated with hematoxylin & eosin stain, immunohistochemical stains, and DNA flow cytometric studies. RESULTS: It included 6 benign and one malignant case. The progesterone receptor, vimentin, neuron-specific enolase, and chromogranin A showed diffused positive stain in all cases. Estrogen receptor and P53 stain were negative in all 7 patients. Synaptophysin stain was negative in 6 no recurrence patients, but was positive only in the patient who suffered from recurrence. DNA flow cytometry showed diploid results in six non-malignant tumors. In the malignant patient, the tumor in the first operation showed diploid result, but tumors in second and third operations showed aneuploidy. CONCLUSIONS: Solid and pseudopapillary tumor of the pancreas should be considered as a potentially malignant disease in all patients and regular follow-up is mandatory.     

DNA aneuploidy and proliferation in spontaneous human and dimethylhydrazine-induced murine colorectal carcinogenesis.

DNA aneuploidy and proliferative abnormalities were studied by flow cytometry in 169 colorectal specimens from 162 patients. Of 37 adenomas, three showed aneuploidy and another seventeen revealed a "near diploid" DNA pattern. The rate of aneuploid and "near diploid" DNA changes in 92 carcinomas was 53.3% and 23.9%, respectively. No correlation was seen between the ploidy distribution and the stage or histologic grade of the carcinomas. The S-phase fractions of both adenomas and carcinomas significantly increased from the diploid (8.1 +/- 0.8% and 7.8 +/- 0.9% respectively; mean +/- SEM) to the "near diploid" (14.9 +/- 1.2% and 12.6 +/- 1.5%) and aneuploid (20.4 +/- 1.3% and 11.4 +/- 1.6%) lesions. To better understand neoplastic progression at very early stages, flow cytometry was also performed on 195 colonic specimens of 44 rats treated by weekly subcutaneous injections of 21 mg/kg Dimethylhydrazine. There was a single "near diploid" carcinoma in this group, and all other induced neoplasms (39 carcinomas and 27 adenomas) revealed a diploid DNA pattern. The S-phase fractions were as follows: controls (38 untreated animals) 8.6 +/- 0.1%, normal mucosa (of Dimethylhydrazine exposed rats) 10.1 +/- 0.25% (p less than 0.0001), adenomas 13.9 +/- 0.6% (p less than 0.01), and carcinomas 14.7 +/- 0.6% (p less than 0.01). These findings support the conclusion that genomic alterations and proliferative abnormalities may already be present in premalignant human colonic lesions. However, despite strong morphological similarities, major biological differences exist between the Dimethylhydrazine-induced murine intestinal carcinogenesis and spontaneously occurring human colorectal neoplasms.