Cytologic diagnosis of malignant mesothelioma in serous effusions using an antimesothelial-cell antibody.

Differentiating mesothelioma, reactive mesothelium, and adenocarcinoma in serous effusions is often difficult, despite the application of ancillary techniques in support of the traditional cytomorphologic criteria. A polyclonal antimesothelial-cell antibody recently developed by our group was evaluated as a histogenetic marker on a series of primary (n = 12) and metastatic (n = 12) malignant effusions. Immunostaining was performed on paraffin sections from cell blocks. All mesothelioma effusions stained positive for the antibody, whereas, in contrast, all metastatic carcinoma specimens failed to react. These results (100 percent specificity and 100% sensitivity for mesothelioma) provide a basis for a reliable use of the antibody in the cytologic examination of suspicious or malignant serous effusions.     

Tubal metaplasia: A cytologic study with comparison to other neoplastic and non-neoplastic conditions of the endocervix

Tubal metaplasia of the endocervix (TME), a condition that may be con/used morphologically with glandular neoplasia, is frequently found in cone or hysterectomy specimens. To determine the frequency of detecting TME in cytologic smears, we retrospectively reviewed 28 Papanicolaou (Pap) smears from 22 women (mean age 39.1 yr; range 25-60 yr) with histologically proven TME. Our criteria for TME were the presence of two cell types in addition to endocervical secretory cells, i.e., peg cells (cells with dark and granular cytoplasm and elongate nuclei) and ciliated cells. All women had cervical cytology specimens obtained with an endocervical brush shortly before the procedures in which TME was diagnosed, and five also had at least one post-procedure smear. Of 20 smears with an adequate, non-neoplastic endocervical component, TME was found in 2 (10%). In these two, TME cells constituted 10% and < 5% of all the glandular cells, respectively, and the percentage of ciliated cells in the TME was approximately 25% and 75%. In conclusion, TME was noted infrequently (10%) on the cervical cytosmears of women with histologically-proven TME. This result corresponds to the histologic finding that TME typically involves the upper endocervix and glandular epithelium, with only 13% of the women having TME on the surface of the lower endocervix. Atypical glandular cells on cervical cytology are a problem for clinicians and pathologists alike. The differential diagnosis of such atypia, including TME, cells of the lower uterine segment, squamous intraepithelial lesion in glands and glandular neoplasia, is discussed.     

Expression of cyclin D1, retinoblastoma gene protein, and p16 MTS1 protein in atypical adenomatous hyperplasia and adenocarcinoma of the lung

 To clarify the events leading to the disruption of cell growth control that occurs during the development of pulmonary adenocarcinoma (AC), we used immunohistochemistry to evaluate the expression of G1 cycle regulators, cyclin D1, Rb protein (pRb), and p16 MTS1 protein and the tumour proliferation marker, Ki 67, both in AC of the lung and in its precursor lesion, atypical adenomatous hyperplasia (AAH). The frequency of lesions with cyclin D1 overexpression was relatively high in AAH (47–89%), but was decreased in early AC (28%) and overt AC (35%). The loss of pRb expression was rare in both AAH (0–18%) and early AC (0%), and was infrequent even in overt AC (13%). The loss of p16 expression was also relatively infrequent in both the premalignant and the malignant lesions (11–25%). Our results suggest that overexpression of cyclin D1 is an early event and plays an important part in tumorigenesis in the case of lung AC. However, cyclin D1 overexpression is not required for the development and maintenance of a malignant phenotype. It is likely that some cyclin D1-independent pathways other than Rb and p16 abnormalities have an important role in the malignant transformation from AAH to early AC. Received: 8 July 1997 / 26 September 1997     

Utility of cytokeratin 20 in identifying the origin of metastatic carcinomas in effusions

Using a commercially available monoclonal antibody (K_s20.1) and the avidin-biotin peroxidase method on cytospins and cell blocks, we analyzed cytokeratin (CK) 20 expression in 169 serous effusions. Cytoplasmic staining was observed in 44/151 malignant fluids. Colon, gastric, and pancreatic adenocarcinomas and mucinous ovarian tumors were most frequently positive. Single cases of transitional-cell and squamous cell carcinomas were reactive as well. Lung and breast cancers were mostly negative. Nonmucinous ovarian tumors were invariably unlabeled as were mesotheliomas and normal mesothelial cells. the study shows that CK 20 is valuable in distinguishing tumor cell origin in effusions. in particular, it identifies a set of carcinomas with the majority arising from the gastrointestinal tract, and represents a highly characteristic marker for colorectal cancer. © 1995 Wiley- Liss, Inc.     

奥替普拉诱发人肺腺癌细胞凋亡的研究

目的探讨奥替普拉（ｏｌｔｉｐｒａｚ）能否诱发人肺腺癌细胞凋亡及其机制。方法应用光镜、ＤＮＡ电泳、流式细胞仪、活细胞视频观察进行检测和分析。结果癌细胞在奥替普拉作用下,细胞分裂阻滞在分裂中期,Ｇ２／Ｍ百分比增高,出现细胞凋亡峰,凋亡细胞出现胞体固缩、核染色质凝聚或者断裂,细胞ＤＮＡ裂解片段呈现典型的“梯形”条带。奥替普拉诱导的ＧＬＣ细胞凋亡在使用浓度１２０μｇ／ｍｌ时效果明显。结论奥替普拉在适当浓度时能够诱发人肺腺癌细胞凋亡,这种作用与分裂期阻滞密切相关。     

上皮性钙粘附蛋白和β-连环素的表达与胆囊腺癌预后的关系

目的　探讨上皮性钙粘附蛋白 (E cad)及 β 连环素 (β cat)在胆囊腺癌中的表达及其与分化、转移、临床分期和预后的关系。方法　免疫组织化学法 (SP法 )和原位杂交法。结果　免疫组织化学法 :60例胆囊腺癌中E cad及 β cat的阳性率分别为 40 %和 45 % ,异常表达率分别为 58 3 %和 63 3 %。E cad和 β cat的异常表达率与胆囊腺癌的分化程度有相关性 (P <0 0 5) ,在有淋巴结转移病例中E cad及 β cat的异常表达率明显高于无转移病例 ,随着临床分期由Ⅰ期到Ⅳ期 ,E cad及 β cat异常表达率明显增高 (P <0 0 5)。E cad和 β cat异常表达病例的平均生存时间和 5年生存率明显低于正常表达病例。原位杂交法 :胆囊腺癌中E cad和 β catmRNA的阳性率分别为 60 %和 40 % ,与蛋白正常表达一致率分别为 78 8%和 82 4%。结论　检测 β cat或E cad和 β cat的共同表达是指导临床治疗及估计预后有意义的指标 ,可应用临床预后的综合评估     

垂体腺瘤PTTG、bFGF mRNA表达与侵袭性的关系

目的：检测垂体腺瘤组织中垂体肿瘤转化基因(PTTG）、bFGF mRNA的表达，分析其与垂体腺瘤侵袭性的关系及临床意义。方法：应用逆转录PCR(RT—PCR)方法检测30例垂体腺瘤组织标本中PTTG、bFGF mRNA的表达，分析二者与垂体腺瘤侵袭性的关系。结果：侵袭性垂体腺瘤组的PTTG、mRNA表达、bFGF mRNA表达均较非侵袭性腺瘤组增高，其差异具有统计学意义。结论：垂体腺瘤侵袭性的发生与垂体肿瘤转化基因(PTTG)表达增高及其上调血管生成正调节因子bFGF并表达、促进血管生成有关，     

孕激素治疗子宫内膜癌的形态学观察与治疗机理探讨

目的：通过孕激素对子宫内膜腺癌治疗后的形态观察，而探讨其治疗机理。方法：对我院经孕激素治疗并手术切除的４２例子宫内膜腺癌标本及３４例未用孕激素治疗的子宫内膜腺癌诊刮标本，进行光镜、电镜的腺癌细胞形态学观察。结果：孕激素治疗后的腺癌细胞分化趋向成熟，其分泌活跃，同时，还在癌组织中观察到凋亡的腺癌细胞。未经孕激素治疗的子宫内膜腺癌细胞，其组织排列紊乱，极性消失，有些腺体呈背靠背现象。结论：孕激素对肿瘤细胞有直接作用，使癌细胞生长受抑，促使其分化转向成熟，术前与术后应用孕激素治疗，可减少腹腔种植及转移，减少术后复发机会。     

Human papillomavirus type 18 DNA sequences in adenocarcinoma and adenosquamous carcinoma of the uterine cervix

Human papillomavirus (HPV) DNA sequences were detected by Southern blot hybridization and polymerase chain reaction (PCR) in 10 out of 19 patients (52.7%) with adenocarcinoma [15] and adenosquamous [4] carcinoma of the uterine cervix. HPV 18 DNA was detected in 8 of these 19 patients (42.1%), HPV 16 DNA in 1 patient (5.3%) and HPV type X (unknown) in another (5.3%). Of the 10 HPV positive samples HPV 18 was found in 6 out of 6 pure adenocarcinomas (100%), and in 2 of 4 (50%) adenosquamous carcinomas. HPV 16 and HPV X were each detected in 1 out of 4 (25%) adenosquamous carcinomas. The physical state of the viral DNA was investigated in 5 of the 10 HPV-positive cases. All the specimens from these 5 cases showed HPV to be integrated into the host genome, except for one adenosquamous specimen, which showed both episomal and integrated forms of HPV 16. Six of 8 HPV 18 DNA positive specimens were from cases of pure adenocarcinoma and it was found by PCR that five of these 6 specimens retained fragments of E6/E7, LCR/E7 and early sequence of E1 fragment (sequence: 1188–1373) but deleted most part of E1.