胃微囊型及粘液型印戒细胞癌

应用电镜、光镜及免疫组化法对９例胃印戒细胞癌进行研究，发现大部分印戒细胞癌是由胞质内大量粘液颗粒积聚所致少数则由胞质内微囊形成所致。由此，我们把胃印戒细胞癌分为粘液型和微囊型两型。根据癌细胞质中有无粘液分泌颗粒，粘液印戒细胞癌又可分为颗粒型，粘液池型和中间型３种亚型。     

Distinction of differentiated type early gastric carcinoma with gastric type mucin expression

BACKGROUND: Intestinal and diffuse gastric carcinomas differ in morphology and growth behavior. Differentiated type gastric carcinoma (DGC), which corresponds roughly with the intestinal type of Lauren, can demonstrate phenotypic properties associated with mucin expression and brush border. However, their clinical significance is controversial. A classification based on mucin phenotype and brush border was performed to determine the clinicopathologic diversity of DGCs in their early stage. METHODS: A total of 120 specimens from 116 DGC patients with definite submucosal invasion were evaluated both macroscopically and histologically. All sections were examined immunohistochemically with human gastric mucin, Muc-2, and CD10 and with mucin histochemically with paradoxical concanavalin A staining and high iron Diamine-Alcian Blue. They were classified into gastric type (G-type), intestinal type (I-type), mixed gastric and intestinal type (M-type), or null type (N-type) phenotypes. The immunoreactivity of E-cadherin and beta-catenin also was investigated to determine the correlation between mucin phenotype and clinicopathologic factors. RESULTS: The G-type phenotype was found to be in contrast to I-type: G-type was an independent factor associated with lymph node metastasis. Significant correlations were observed between the G-type phenotype and the complex type carcinoma found that was histologically: lymphatic invasion, lymph node metastasis, and the abnormal expression of E-cadherin. A significant difference in the proportion of mucin phenotypes between papillary type and tubular type carcinoma was observed. G-type was found to be the predominant phenotype in papillary carcinoma in contrast to tubular carcinoma. CONCLUSIONS: The G-type mucin phenotype and papillary adenocarcinoma should be distinguished from other types of DGCs because of their increased malignant potential in the incipient phase of invasion and metastasis. The significance of G-type and papillary adenocarcinoma should be reflected in the treatment of patients with early stage DGCs, including endoscopic mucosal resection.     

Compensation of type I and type II cytokeratin pools in lung cancer

Cytokeratins (CKs) constitute the largest family of intermediate filament proteins, and are subdivided into type I (CK9-CK23) and type II (CK1-CK8) subclasses. CK19 is expressed in non-small cell lung cancer (NSCLC), and serum CK19 fragment (referred to as CYFRA21-1) is one of the tumor markers used in diagnosing NSCLC. Type I and type II CKs have been shown to form obligate 1:1 heteropolymers, suggesting that dynamic changes must occur in the expression levels of CK pools when one CK is suppressed. However, the absolute levels of CK expression and their dynamic changes have not been fully evaluated. Therefore, we quantitatively determined CK expression levels in NSCLC cell lines, and evaluated the rate of change of CK expression levels after RNA interference targeting of single CKs. In NSCLC cells, type I CK18 and type II CK8 are the dominant CKs, with absolute expression levels of 12-77pmol/10(6)cells, while the expression patterns of the CKs vary among cell lines. Moderate suppression of a single dominant CK caused downregulation in CKs of the complementary type, and upregulation of other CKs of the same type. In contrast, severe suppression of a single dominant CK caused almost complete suppression of all CKs. In addition, introduction of CK19 led to resistance to CK degradation by CK18 suppression. These data suggest the presence of a critical threshold expression level for a dominant CK and a role for CK19 in the compensation of type I and type II CK pools in NSCLC.     

The role of type of tobacco and type of alcoholic beverage in oral carcinogenesis

Incidence rates of oral and oropharyngeal cancers (oral cancer) in Spain are among the highest in Europe. Spain has a population heavily exposed to various types of tobacco and alcoholic beverages but the role and impact of tobacco type and beverage type in oral carcinogenesis remain controversial. To estimate the independent and joint effects of tobacco smoking and alcohol drinking habits on the risk of developing oral cancer, we carried out a multicenter, hospital-based, case-control study in Spain. Data from 375 patients newly diagnosed with cancer of the oral cavity or oropharynx and 375 matched control subjects were analyzed using multivariate logistic regression procedures. All exposure characteristics of amount, duration and cessation of both tobacco smoking and alcohol drinking were strongly associated with cancer risk following a dose-dependent relationship. At equal intake or duration levels, black-tobacco smoking and drinking of spirits were both associated with a 2- to 4-fold increase in cancer risk compared to blond tobacco smoking or drinking of wine or beer, respectively. While ever exposure to smoking only or drinking only was associated with a moderate and nonsignificant increase in cancer risk, a history of simultaneous exposure to both habits was associated with a 13-fold increase that was compatible with a synergistic effect model (p-value for interaction: 0.008). Exposure to black tobacco smoking and/or drinking of spirits may account for up to 77% of oral cancer occurrence in Spain. Both black tobacco smoking and drinking of spirits place individuals at a very high risk of developing oral cancer. Simultaneous exposure to tobacco and alcohol consumption increases oral cancer risk in a synergistic fashion, even when consumption levels are moderate. These results underline the importance of type of tobacco and alcohol concentration in oral carcinogenesis.     

Cytological features of complex type fibroadenoma in comparison with non-complex type fibroadenoma

Background

To determine the cytomorphological features of complex type fibroadenoma (CFA), we reviewed fine needle aspiration (FNA) cytology with correlation to its histopathology findings, and compared them with non-complex type fibroadenoma (NCFA).

Methods

From excisional biopsy or resected specimens of fibroadenoma (FA) cases treated at our institution from 2004 to 2013, we chose 46 patients who underwent FNA before a diagnosis of FA was established. We histologically re-classified them into two groups: CFA and NCFA. FNA diagnosis was retrospectively re-evaluated from FNA reports. We further re-assessed detailed characteristics of each FNA smears to identify cytomorphological features of CFA.

Results

We found that 15 cases fulfilled the diagnostic criteria of CFA, in which 7 (46.7 %) had an FNA diagnosis of “suspicious for malignancy” or “indeterminate” while only 2 NCFA cases had that of “indeterminate” (p = 0.004). FNA smears from CFA cases showed discohesiveness, enlarged nuclei, prominent nucleoli, and fewer myoepithelial cells more often than NCFA. Although no significant difference was noted in patients’ age and tumor size between CFA and NCFA, 5 CFA cases (33.3 %) were accompanied by the presence of carcinoma in the same breast or the contralateral breast while no NCFA cases had carcinoma in the breast.

Conclusions

FNA of CFA can lead to erroneous or indeterminate interpretation, due to proliferative and/or hyperplastic changes of ductal epithelium with or without atypia. It is important to recognize the disease entity and characteristic cytomorphological findings of CFA to reach accurate FNA diagnosis of breast lesions.

     

Increased infectivity of adenovirus type 5 bearing type 11 or type 35 fibers to human esophageal and oral carcinoma cells

Esophageal and oral carcinomas are relatively resistant to adenovirus serotype 5 (Ad5)-mediated gene transfer, primarily because expression of the cellular receptors for Ad5, the coxsackievirus and adenovirus receptor, is often downregulated in these types of tumor. The types of Ad in which the receptor expression is not suppressed in tumors are therefore better vectors for gene transfer into tumors. CD46, a cellular receptor for Ad subtype B2, such as Ad11 and Ad35, is well expressed in a number of esophageal and oral tumor cells. Since the infectivity of Ad to target cells is mainly influenced by the interaction between their fibers and the cellular receptors, we examined the infectivity of chimeric Ad5, whose fiber structure was substituted with that of type 11 or 35 (Ad5/11 or Ad5/35), to 6 human oral and 11 esophagus carcinoma cells. We found that the chimeric Ad, in particular Ad5/35, infected more effectively than Ad5 in all the tumors tested. However, the efficacy of Ad5/35- and Ad5/11-mediated transduction was not correlated with the expression level of CD46 or CD80/86, a cellular receptor of the Ad subtype B1, in the target cells. These data suggest that the Ad subtype B2 are suitable vectors of gene transfer for human squamous cell carcinomas of the upper gastrointestinal tract, and that the infectivity of the Ad subtype B2 can possibly be regulated by other receptors besides CD46.     

COMPARISON OF ELECTRON MICROSCOPIC OBSERVATIONBETWEEN EXPANSIVE TYPE AND INFILTRATIVE TYPEOF HEPATOCELLULAR CARCINOMA

Expansivehepatocellularcarcinoma(EHCC)isatypeofHCCwithfavorableprognosis.Sinceitwasfirstreportedattheendof1970s',['-']manyscientistshavepaidattentiontoitsbiologicalcharacteristics.TheultrastructureofHCCwereearlierreportedinthe1960s'includingcasereports,l#]systematiccaseswereanalyzedl'-']andspecialcasereportetc.Butasfarasweknow,therestillhasbeennosystematicreportoftheultrastructureofEHCCintheLiterature.Westudied20casesofEHCCand20casesofIHCCbytransmissionelectronmicroscopetot'indtherel…     

Lymphoma type adult T-cell leukemia--a clinicopathologic study of HTLV related T-cell type malignant lymphoma

The clinical and pathological features of T-cell type malignant lymphoma related to human T-cell leukemia virus (HTLV) were investigated in eight patients presenting lymphadenopathy. Biopsy of lymph nodes showed an histology of diffuse non-Hodgkin's lymphoma. All patients were positive for anti-ATLA antibody and HTLV proviral DNA in the lymph node cells. Most patients showed pronounced hypercalcemia and high serum levels of lactic dehydrogenase. All patients died between 3 and 17 months (mean 8 months) after the onset of disease. HTLV-related malignant lymphoma should be added to the spectrum of ATL, being classified as a lymphoma type ATL.     

Serologic assessment of type 1 and type 2 immunity in healthy Japanese adults.

We assessed the informativeness of several serologic biomarkers of immune function using serum specimens collected in the Miyazaki Cohort Study from subjects who were seronegative for anti-human T-cell lymphotrophic virus I and anti-hepatitis C virus. To broadly characterize type 1 immune status, we measured EBV antibody titers, because titer profiles associated with cellular immune suppression are well described. We also tested for three type 2 biomarkers: total serum IgE, soluble CD23, and soluble CD30. Nonreactivity to a tuberculin purified protein derivative (PPD) skin test is indicative of diminished delayed-type hypersensitivity (type 1) responsiveness in the study population due to a history of tuberculosis exposure or Bacillus Calmette-Guérin vaccination. We therefore evaluated the serologic markers as predictors of PPD nonreactivity using logistic regression. Subjects whose EBV antibody profiles were consistent with deficient type 1 immunity were more than thrice as likely to be PPD nonreactive as persons with "normal" antibody titers. Elevated total IgE was also strongly associated with PPD nonreactivity (odds ratio 3.4, 95% confidence interval 1.2-9.9); elevated soluble CD23 had a weaker, but positive, odds ratio, whereas soluble CD30 levels were not predictive of PPD status. Therefore, PPD nonreactivity is associated, in this population, with a pattern of serum biomarkers that is indicative of diminished type 1 and elevated type 2 immunity. We conclude that, with the exception of soluble CD30, the serologic markers are informative for the characterization of type 1/type 2 immune status using archived sera from study populations of healthy adults.     

Diagnostic values of serum type III procollagen N-terminal peptide in type IV gastric cancer

Since increased synthesis of collagen has been demonstrated in tissue of type IV gastric cancer, we attempted to distinguish type IV gastric cancer from other cancers by measuring serum levels of type III procollagen N-terminal peptide (type III-N-peptide). Mean serum levels in type IV gastric cancer patients without metastasis were found to be elevated above normal values and developed a tendency to be higher than those in types I, II and III gastric cancer patients without metastasis. Highly positive ratios were found in patients with liver diseases including hepatoma and colon cancer, biliary tract cancer, and esophageal cancer patients with liver, lung or bone metastasis, but only 2 out of 14 of these cancer patients without such metastasis showed positive serum levels of type III-N-peptide. Positive cases in patients with type IV gastric cancer were obtained not only in the group with clinical stage IV but also in the groups with clinical stages II and III. In addition, high serum levels of type III-N-peptide in patients with type IV gastric cancer were seen not only in the cases with liver, lung or bone metastasis but also in cases with disseminated peritoneal metastasis alone. These results suggest that if the serum level of type III-N-peptide is elevated above normal values, type IV gastric cancer should be suspected after ruling out liver diseases, myelofibrosis and liver, lung or bone metastasis.     

Expression of TGF-beta and procollagen type I and type III in human gastric carcinomas

To elucidate the difference between scirrhous and non-scirrhous gastric carcinomas, we examined the expressions of TGF-beta, procollagen type I and type III in 7 gastric carcinoma cell lines and 37 gastric carcinoma tissues, and also examined the effect of TGF-beta on the expression of procollagen mRNA by TMK-I cells. TGF-beta mRNA was detected in all the tumors examined in vivo and in vitro. Interestingly, 9 (90%) of 10 scirrhous gastric carcinomas revealed higher levels of TGF-beta mRNA than normal tissues, while 8 (38%) of 21 well-differentiated adenocarcinomas had higher TGF-beta mRNA levels than normal tissues. As for procollagen mRNA, most of the human gastric carcinoma cell lines expressed type-I procollagen mRNA and MKN-I expressed type-III procollagen mRNA. Furthermore, procollagen type-I mRNA accumulation in TMK-I cells was increased by exogenous TGF-beta. Most of the tumor tissues from surgical specimens expressed higher procollagen mRNA than normal tissues. These results indicate that TGF-beta produced by carcinoma cells might stimulate collagen synthesis not only by fibroblasts but also by carcinoma cells themselves, leading to diffuse fibrosis of scirrhous gastric carcinomas.     

人乳头状瘤病毒16和18型感染与乳腺增生症和乳腺癌的关系

目的:探讨人乳头状瘤病毒(human papil-lomavirus HPV)16、18型感染与乳腺增生症、乳腺癌的关系。方法:采用原位杂交法检测HPV16、HPV18在正常乳腺组织、乳腺增生组织和乳腺癌中的表达。结果:HPV16在乳腺癌、乳腺增生症及正常乳腺组织各60例中的感染率分别为51·67%(31/60)、31·67%(19/60)和11·67%(7/60),差异有统计学意义,P<0·05;HPV18感染率分别为56·67%(34/60)、35·00%(21/60)和15·00%(9/60),差异有统计学意义,P<0·05;HPV16和18在乳腺癌、乳腺增生症及正常乳腺组织中的共感染率分别为48·33%(29/60)、15·00%(9/60)和6·67%(4/60),其中乳腺增生症与正常乳腺组织共感染率差异无统计学意义,而与乳腺癌差异有统计学意义,P<0·01。结论:本组乳腺癌和乳腺增生症组织中HPV16和HPV18感染率明显高于正常乳腺组织中的感染率;HPV16和HPV18感染与乳腺增生、乳腺癌的关系有待进一步探讨。     

人乳头状瘤病毒16和18型感染与乳腺增生症和乳腺癌的关系

目的：探讨人乳头状瘤病毒（human papillomavirus HPV）16、18型感染与乳腺增生症、乳腺癌的关系。方法：采用原位杂交法检测HPV16、HPV18在正常乳腺组织、乳腺增生组织和乳腺癌中的表达。结果：HPV16在乳腺癌、乳腺增生症及正常乳腺组织各60例中的感染率分别为51．67％（31／60）、31．67％（19／60）和11．67％（7／60），差异有统计学意义，P〈0．05；HPV18感染率分别为56．67％（34／60）、35．00％（21／60）和15．00％（9／60），差异有统计学意义，P〈0．05；HPV16和18在乳腺癌、乳腺增生症及正常乳腺组织中的共感染率分别为48．33％（29／60）、15．00％（9／60）和6．67％（4／60），其中乳腺增生症与正常乳腺组织共感染率差异无统计学意义，而与乳腺癌差异有统计学意义，P〈0．01。结论：本组乳腺癌和乳腺增生症组织中HPV16和HPV18感染率明显高于正常乳腺组织中的感染率；HPV16和HPV18感染与乳腺增生、乳腺癌的关系有待进一步探讨。