周围型肺鳞癌与周围型肺腺癌的螺旋CT动态增强对照

目的 对照分析周围型肺鳞癌与周围型肺腺癌的CT动态增强表现,探讨CT动态增强对鉴别周围型肺鳞癌与周围型肺腺癌的价值。方法 对30例周围型肺鳞癌与40例周围型肺腺癌进行CT动态增强扫描,测量增强前后各次扫描时的CT增强值,根据CT增强值绘出动态增强曲线,并观察增强模式。结果 周围型肺腺癌的增强峰值与峰值到达时间与周围型肺鳞癌相比,差异无统计学意义（P〉0．05）。当病灶〉3cm时,两组的增强模式差异无统计学意义（P〉0．05）;当病灶≤3cm时,两组的增强模式差异有统计学意义（P〈0．05）,腺癌以均匀增强为主,鳞癌以不均匀增强或周边增强为主。结论 根据增强峰值与峰值到达时间不能鉴别周围型肺鳞癌与周围型肺腺癌;当病灶≤3cm时,周围型肺鳞癌的增强模式不同于周围型腺癌。     

上皮钙粘附素在宫颈鳞癌中的表达及临床意

 目的　研究上皮钙粘附素 (E- cadherin,ECD)在宫颈鳞癌中的表达及其临床意义。方法　采用 SP免疫组化染色方法 ,检测 42例宫颈鳞癌中 ECD的表达 ,并进行生存分析。结果　 (1 )宫颈鳞癌中 ECD有胞膜和胞浆两种表达形式。 、 级鳞癌中 ECD胞膜的高表达 (2 0 /31 )明显高于 级 (2 /1 1 ) (P<0 .0 5) ;淋巴结转移组 ECD胞浆的高表达 (1 1 /1 3)明显高于未转移组 (8/2 0 ) (P<0 .0 5)。 (2 ) ECD胞膜表达与胞浆表达呈显著负相关 (P<0 .0 1 )。 (3) ECD胞膜低表达或 /和胞浆高表达与细胞失分化、淋巴结转移及低生存率有关 (P<0 .0 5)。结论　 ECD胞膜低表达和 /或胞浆高表达是宫颈鳞癌不良预后的重要判断指标。     

Stainability of lung cancer cells with Leu-7 and OKT-9 monoclonal antibodies

One hundred and one cases of lung cancer were immunohistochemically studied for stainability with Leu-7 (anti-myelin fiber associated glycoprotein) and OKT-9 (anti-transferrin receptor) monoclonal antibodies. All small cell carcinomas and carcinoid tumors were positively stained by Leu-7, and 22 of 41 differentiated adenocarcinomas were also positively stained, especially well-differentiated Clara cell-type adenocarcinoma, (11/14 cases). However, only one of 26 squamous cell carcinomas, one of six large cell carcinomas, one of six adenosquamous carcinomas and none of 16 poorly differentiated adenocarcinomas were stained by Leu-7. On the other hand, all squamous cell carcinomas (26/26 cases), 10 of the 16 poorly differentiated adenocarcinomas, four of the six large cell carcinomas showed positive membranous staining with OKT-9. However, only one of 41 differentiated adenocarcinomas and no small cell carcinomas nor carcinoid tumors were stained by OKT-9. The stainability of lung cancer by these antibodies is discussed.     

Overexpression and diffuse expression pattern of IQGAP1 at invasion fronts are independent prognostic parameters in ovarian carcinomas

IQGAP1 is a multifunctional protein involved in actin cytoskeleton assembly and E-cadherin-mediated cell adhesion. To determine the role of IQGAP1 in ovarian tumors, we evaluated IQGAP1 expression by immunohistochemistry in 17 adenomas, 30 borderline tumors and 80 adenocarcinomas and its relation with patient survival. IQGAP1 was overexpressed in adenocarcinomas compared with adenomas and borderline tumors. Enhanced immunostaining in invasive tumor fronts was categorized as focal or diffuse. The diffuse expression pattern correlated with high histological grade and clinicopathological stages. IQGAP1 overexpression and diffuse invasion pattern were significantly associated with poor prognosis by multivariate analysis. Our findings suggest the involvement of IQGAP1 in the progression and spread of ovarian adenocarcinomas. Overexpression and diffuse expression pattern of IQGAP1 are potentially useful independent molecular predictors of highly aggressive ovarian carcinomas.     

Clinicopathologic characteristics of adenosquamous carcinoma of the lung

Fifty-six cases of surgically resected adenosquamous carcinoma of the lung were studied clinicopathologically, and their outcome was compared with that of adenocarcinomas and squamous cell carcinomas of the lung. The frequency rate of adenosquamous carcinoma was 2.6% of 2160 primary lung cancers resected in the National Cancer Center Hospital (Tokyo, Japan). The survival curves of patients with adenosquamous carcinomas, adenocarcinomas, and squamous cell carcinomas indicated that the outcome of adenosquamous carcinoma was poorer than that of adenocarcinomas and squamous cell carcinomas, particularly in Stages I and II. The amount of adenocarcinoma component did not affect the survival rate, although the histologic features of metastatic lymph nodes was somewhat influenced by the histologic type of the primary tumors. The histologic subtype of adenosquamous carcinoma was one of the independent prognostic determinants.     

Folate receptor alpha expression in lung cancer: diagnostic and prognostic significance

With the advent of targeted therapies directed towards folate receptor alpha, with several such agents in late stage clinical development, the sensitive and robust detection of folate receptor alpha in tissues is of importance relative to patient selection and perhaps prognosis and prediction of response. The goal of the present study was to evaluate the expression of folate receptor alpha in non-small cell lung cancer specimens to determine its frequency of expression and its potential for prognosis. The distribution of folate receptor alpha expression in normal tissues as well as its expression and relationship to non-small cell lung cancer subtypes was assessed by immunohistochemistry using tissue microarrays and fine needle aspirates and an optimized manual staining method using the recently developed monoclonal antibody 26B3. The association between folate receptor alpha expression and clinical outcome was also evaluated on a tissue microarray created from formalin fixed paraffin embedded specimens from patients with surgically resected lung adenocarcinoma. Folate receptor alpha expression was shown to have a high discriminatory capacity for lung adenocarcinomas versus squamous cell carcinomas. While 74% of adenocarcinomas were positive for folate receptor alpha expression, our results found that only 13% of squamous cell carcinomas were FRA positive (p<0.0001). In patients with adenocarcinoma that underwent surgical resection, increased folate receptor alpha expression was associated with improved overall survival (Hazard Ratio 0.39, 95% CI 0.18-0.85). These data demonstrate the diagnostic relevance of folate receptor alpha expression in non-small cell lung cancer as determined by immunohistochemistry and suggest that determination of folate receptor alpha expression provides prognostic information in patients with lung adenocarcinoma.     

Changes in E-cadherin associated with cytoplasmic molecules in well and poorly differentiated endometrial cancer

E-cadherin function is thought to be impaired in epithelial cancer. To investigate the alterations in E-cadherin associated with cytoplasmic molecules including alpha-catenin, beta-catenin, gamma-catenin, p120CAS, and IQGAP1 in various endometrial cancers with different degree of differentiation, we examined the localization and expression of E-cadherin and cytoplasmic molecules in 30 cases of both well and poorly differentiated endometrioid adenocarcinomas, using immunofluorescence and immunoblotting techniques. E-cadherin and cytoplasmic molecules demonstrated linear staining at the cell boundaries in normal endometrium. In all 20 cases with well differentiated adenocarcinomas, alpha-catenin and IQGAP1 disappeared from the cell adhesive sites, but other cytoplasmic molecules were co-localized with E-cadherin along the cell boundaries. In all 10 cases with poorly differentiated adenocarcinomas, E-cadherin and cytoplasmic molecules accumulated as large aggregates along cell adhesive sites, and the localization of IQGAP1 differed from those of other cytoplasmic molecules. The expression of these molecules in all 20 cases with well differentiated adenocarcinomas decreased or was lost in Triton-insoluble fraction, in comparison with the findings for all cases with normal endometrium or poorly differentiated adenocarcinomas. These results suggested that each alteration in E-cadherin associated with cytoplasmic molecules may play a different role in E-cadherin dysfunction between well and poorly differentiated adenocarcinomas.     

Deletion mapping on the short arm of chromosome 3 in squamous cell carcinoma and adenocarcinoma of the lung.

We examined loss of heterozygosity in 49 adenocarcinomas and 18 squamous cell carcinomas of the lung with 19 RFLP markers on the short arm of chromosome 3. Although no interstitial deletions were observed in any squamous cell carcinomas, interstitial or partial deletions were detected in 23 adenocarcinomas. Identification of two common regions of deletion in adenocarcinomas, at 3p21.3 and 3p14.1-21.1, suggested the presence of at least two tumor suppressor genes on 3p within the same regions commonly deleted in renal cell carcinomas. Correlation between the frequency of loss of heterozygosity on 3p and histopathological grade of adenocarcinoma also was observed. These results imply an etiological difference between two major types of non-small cell lung cancers, adenocarcinoma and squamous cell carcinoma.     

Clinical and histopathologic evaluation of the expression of Ha-ras and fes oncogene products in lung cancer.

The expression of Ha-ras and fes oncogenes was investigated with the immunohistochemical method in formalin-fixed, paraffin-embedded tissue specimens of 147 lung carcinomas. Positive immunoperoxidase reactions for Ha-ras p21 were found in 80.5% of the adenocarcinomas, 39.5% of the squamous cell carcinomas, 21.4% of the large cell carcinomas, and 15.4% of the small cell carcinomas; those for fes P85 were found in 51.2% of the adenocarcinomas, 26.3% of the squamous cell carcinomas, 35.7% of the large cell carcinomas, and 15.4% of the small cell carcinomas. Both Ha-ras p21 and fes P85 were expressed most frequently and most strongly in adenocarcinoma. In addition, adenocarcinoma showed significantly higher incidence of concomitant expression of Ha-ras p21 and fes P85 as compared with other histologic types of lung cancer. Thus, the authors suggest that the cooperative effects of Ha-ras and fes oncogenes are especially important in the carcinogenesis of adenocarcinoma. In adenocarcinoma, the incidence and grade of Ha-ras p21 expression increased with the degree of histologic differentiation, suggesting that Ha-ras oncogene might be related to cellular differentiation. Papillary adenocarcinoma showed more frequent Ha-ras p21 expression in comparison with acinar adenocarcinoma. In well- or moderately differentiated adenocarcinoma, the incidence and grade of Ha-ras p21 immunoreactivity in the cases with poor prognosis were significantly higher than in those with good prognosis if other major prognostic factors were equivalent in the two groups. The authors propose that the expression of Ha-ras p21 may be one of the useful prognostic factors in such carcinomas.     

p185neu expression in human lung adenocarcinomas predicts shortened survival

p185neu is the protein product of the HER2/neu protooncogene. This protein has characteristics of a tyrosine kinase growth factor receptor and is postulated to be important in human carcinogenesis. To define the significance of the expression of this protein in human non-small cell lung cancer, 55 tumors from patients with squamous cell carcinoma (16), adenocarcinoma (29), or large cell carcinoma (10) of the lung were examined for p185neu using immunohistological methods. Five of 16 squamous cell carcinomas and 10 of 29 adenocarcinomas were found to overexpress p185neu relative to levels of expression seen in uninvolved bronchiolar epithelium. For the adenocarcinomas, p185neu expression was associated with older age (66.6 +/- 10.1 versus 57.5 +/- 10.8 years) (P = 0.04) and shortened survival (83.7 +/- 94.1 versus 188.5 +/- 120 weeks) (P = 0.01). In this group, using Cox's multivariate survival analysis, p185neu expression was found to be a significant determinant of survival (P = 0.04) even after accounting for the effect of tumor stage. For the squamous cell carcinomas, p185neu expression was not correlated with any of our clinicopathological parameters. Our findings indicate that non-small cell lung cancers which express p185neu do so at levels higher than that found in normal bronchiolar epithelium, and expression in adenocarcinomas of the lung is independently associated with diminished survival intervals.     

Immunocytochemical study of RAS oncoprotein in cytologic specimens of primary lung tumours

We have examined the distribution of ras p21 oncoprotein expression in cytologic specimens from 73 primary bronchial carcinomas using an immunocytochemical analysis. The cytologic preparations studied represent the two major groups of histological types of lung cancer: Small Cell Lung Carcinoma (SCLC) and Non-Small Cell Lung Carcinoma (NSCLC) (squamous cell carcinoma and adenocarcinoma). The differential expression of ras p21 oncoprotein correlated with histological classification and was found in 30% of 23 small cell lesions, 61% of 28 squamous cell lung carcinomas and 32% of 22 adenocarcinomas. The ras p21 oncoprotein was commonly expressed in NSCLC cases (48%) as compared to SCLC cases (30%).     

Survivin in esophageal cancer: An accurate prognostic marker for squamous cell carcinoma but not adenocarcinoma

We quantified the expression of survivin, both as mRNA in real-time PCR and protein in immunohistochemistry, in tumor samples of 112 patients with esophageal cancer (56 squamous cell carcinomas and 56 adenocarcinomas). Overall survival of squamous cell carcinoma patients with high survivin mRNA levels was significantly less than that of patients with low survivin mRNA levels (p = 0.0033). Distribution pattern of survivin (nuclear vs. cytoplasmic or mixed) was not correlated to survival, while the extent of immunostaining was significantly correlated to survivin mRNA values (p = 0.016) and had prognostic relevance in univariate analysis (p = 0.0012). Cox's proportional-hazard regression model showed that tumor survivin expression in esophageal squamous cell carcinoma was the most important prognostic factor, independent of tumor stage and other histopathological factors, both as mRNA relative value (p = 0.0259) and protein immunostaining (p = 0.0147). In esophageal adenocarcinoma, survivin expression and pattern of distribution had no prognostic relevance. Thus, quantifying survivin expression provides a prognostic marker only for esophageal squamous tumors.     

RON及其变异体在肺癌中的表达

目的研究RON及其变异体在肺腺癌中的表达及意义。方法应用免疫组化方法检测106例肺腺癌及35例肺鳞癌中RON的表达情况,并结合临床资料进行统计学分析;通过Western-Blot技术检测31例新鲜肺腺癌组织及9例肺鳞癌组织中RON及其变异体的表达情况,并对RON在不同组织学分级和不同组织学类型中的表达进行统计学分析。结果RON在肺腺癌及鳞癌中都有不同程度的表达,两组比较RON的表达差异具有统计学意义（P〈0.05）;不同分化程度的肺腺癌比较,RON的表达也有差异,低分化的肺腺癌明显高于中分化的腺癌和高分化的腺癌（P〈0.05）;Western-Blot结果显示在肺腺癌和肺鳞癌中均有RON表达;在肺腺癌中观察到RON的变异体,而肺鳞癌中则没有。结论肺癌组织中有RON的过表达,并且肺腺癌中RON的表达明显高于鳞癌（P〈0.05）。肺腺癌中RON的表达与肿瘤分级相关,并存在变异体,而鳞癌则无变异体的表达。     

Expression of C4.4A in precursor lesions of pulmonary adenocarcinoma and squamous cell carcinoma

The protein C4.4A, a structural homologue of the urokinase-type plasminogen activator receptor, is a potential new biomarker in non-small cell lung cancer, with high levels of expression recently shown to correlate to poor survival of adenocarcinoma patients. In this study, C4.4A immunoreactivity in precursor lesions of lung squamous cell carcinoma and adenocarcinoma was investigated by stainings with a specific anti-C4.4A antibody. In the transformation from normal bronchial epithelium to squamous cell carcinoma, C4.4A was weakly expressed in basal cell hyperplasia but dramatically increased in squamous metaplasia. This was confined to the cell membrane and sustained in dysplasia, carcinoma in situ, and the invasive carcinoma. The induction of C4.4A already at the stage of hyperplasia could indicate that it is a marker of very early squamous differentiation, which aligns well with our earlier finding that C4.4A expression levels do not provide prognostic information on the survival of squamous cell carcinoma patients. In the progression from normal alveolar epithelium to peripheral adenocarcinoma, we observed an unexpected, distinct cytoplasmic staining for C4.4A in a fraction of atypical adenomatous hyperplasias, while most bronchioloalveolar carcinomas were negative. Likewise, only a fraction of the invasive adenocarcinomas was positive for C4.4A. With a view to the prognostic impact of C4.4A in adenocarcinoma patients, this finding might suggest that C4.4A could be an early biomarker for a possibly more malignant subtype of this disease.     

肺癌18F-FDG-PETCT的SUVmax与淋巴结转移及肺癌肿瘤标志物之间的关系研究

目的:研究肺癌18F-FDG-PETCT的SUVmax(最大标准摄取值)与肺癌淋巴结转移、肺癌肿瘤标志物、肿瘤大小及临床病理类型之间的关系。方法:经病理确认的98例肺癌住院患者,术前一周内均行18F-FDG PET-CT检查肿块大小、SUVmax及肺门或纵隔淋巴结转移情况;并进行肿瘤标志物神经元特异性烯醇化酶(NSE)、癌胚抗原(CEA)和细胞角蛋白片(CYFRA21-1)检查,统计学分析检测结果。结果:原发灶SU-Vmax与原发灶大小之间存在相关性(r=0.497,P<0.05),与单个肿瘤标志物的值之间无明显相关性。整体分析时肺门或纵隔淋巴结转移组与无转移组的原发灶SUVmax均值之间差异无统计学意义,腺癌肺门或纵隔淋巴结转移组及无转移组的SUVmax均数之间差异有统计学意义(P<0.05)。鳞癌肺门或纵隔淋巴结转移组及无转移组的SUVmax均数之间差别无统学意义(P=0.721)。肺鳞癌与腺癌SUVmax均值之间比较差异有统计学意义(P=0.001);细支气肺泡癌与其它腺癌SUVmax均值之间差异有统计学意义(P<0.05)。结论:在病理类型不明确的情况下原发灶SUVmax的高低并不能预测淋巴结转移的有无,肺腺癌原发灶FDG代谢活性与肺门和(或)纵隔淋巴结转移有关,淋巴结转移率随着肿块SUVmax的增加而增加;肺鳞癌FDG代谢活性与肺门和(或)纵隔淋巴结转移无关。SUVmax与病理类型有关,鳞癌SUVmax较高,腺癌较低,细支气管肺泡癌则更低。     

Stat3 downstream genes serve as biomarkers in human lung carcinomas and chronic obstructive pulmonary disease

Smoking causes lung cancer and chronic obstructive pulmonary disease (COPD) that impose severe health problem to humans. Both diseases are related to each other and can be induced by chronic inflammation in the lung. To identify the molecular mechanism for lung cancer formation, a CCSP-rtTA/(teto)(7)Stat3C bitransgenic model was generated recently. In this model, persistent activation of the Stat3 signaling pathway induced pulmonary inflammation and adenocarcinoma formation in the lung. A group of Stat3 downstream genes were identified by Affymetrix GeneChip microarray analysis that can be used as biomarkers for lung cancer diagnosis and prognosis. To determine which human lung cancers are related to the Stat3 pathway, multiple Stat3 downstream genes were screened in human lung cancers (adenocarcinomas and squamous cell carcinomas) and lung tissue with COPD. In both cancer and COPD, the Stat3 gene was up-regulated. A panel of Stat3-up-regulated downstream genes in mice was up-regulated in human adenocarcinomas, but not in human squamous cell carcinomas. This panel of genes was also modestly up-regulated in lung tissue with COPD from patients with a history of smoking and not up-regulated in those without histories of smoking. Several Stat3-down-regulated downstream genes also showed differential expression patterns in carcinoma and COPD. These studies support a concept that Stat3 is a potent oncogenic molecule that plays a role in formation of lung adenocarcinomas in both mice and humans. The carcinogenesis of adenocarcinoma and squamous cell carcinoma is mediated by different molecular mechanisms and pathways in vivo. Stat3 and its downstream genes can serve as biomarkers for lung adenocarcinoma and COPD diagnosis and prognosis in mice and humans.     

肺癌~（18）F-FDG-PETCT的SUVmax与淋巴结转移及肺癌肿瘤标志物之间的关系研究

目的：研究肺癌18F-FDG-PETCT的SUVmax（最大标准摄取值）与肺癌淋巴结转移、肺癌肿瘤标志物、肿瘤大小及临床病理类型之间的关系。方法：经病理确认的98例肺癌住院患者,术前一周内均行18F-FDG PET-CT检查肿块大小、SUVmax及肺门或纵隔淋巴结转移情况;并进行肿瘤标志物神经元特异性烯醇化酶（NSE）、癌胚抗原（CEA）和细胞角蛋白片（CYFRA21-1）检查,统计学分析检测结果。结果：原发灶SU-Vmax与原发灶大小之间存在相关性（r=0.497,P〈0.05）,与单个肿瘤标志物的值之间无明显相关性。整体分析时肺门或纵隔淋巴结转移组与无转移组的原发灶SUVmax均值之间差异无统计学意义,腺癌肺门或纵隔淋巴结转移组及无转移组的SUVmax均数之间差异有统计学意义（P〈0.05）。鳞癌肺门或纵隔淋巴结转移组及无转移组的SUVmax均数之间差别无统学意义（P=0.721）。肺鳞癌与腺癌SUVmax均值之间比较差异有统计学意义（P=0.001）;细支气肺泡癌与其它腺癌SUVmax均值之间差异有统计学意义（P〈0.05）。结论：在病理类型不明确的情况下原发灶SUVmax的高低并不能预测淋巴结转移的有无,肺腺癌原发灶FDG代谢活性与肺门和（或）纵隔淋巴结转移有关,淋巴结转移率随着肿块SUVmax的增加而增加;肺鳞癌FDG代谢活性与肺门和（或）纵隔淋巴结转移无关。SUVmax与病理类型有关,鳞癌SUVmax较高,腺癌较低,细支气管肺泡癌则更低。     

Adrenomedullin expression does not correlate with survival in lung cancer

It is suggested that adrenomedullin (AM) plays a role in lung carcinogenesis although, to confirm this suggestion, further clinical studies are needed to determine its relationship with prognosis in lung cancer. Archived 50 paraffin-embedded tumor samples of the lung were retrospectively evaluated for AM expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. Quantitation of immunoreactivity was accomplished using an immunohistochemical scoring system. The pulmonary resection specimens contained 22 squamous cell carcinomas, 15 adenocarcinomas, and 13 small cell carcinomas. Non-small cell carcinomas of the lung were more likely to express AM than small cell carcinomas of the lung. Ninety-one percent of squamous cell carcinomas and 87% of adenocarcinomas expressed AM at a moderate to strong level and grade2–4 (30-100%), which were significantly higher from the non-neo-plastic lung tissue. Twenty-three percent of small cell carcinomas of lung expressed AM. Interestingly, AM immunoreactivity was essentially weak and grade 1 (<%30) in this group. AM expression is upregulated in non-small cell carcinomas of the lung, whereas it is downregulated in small cell carcinomas and non-neo-plastic lung tissues. AM expression did not show any correlation with the differentiation of the tumor, the stage of cancer, and the overall survival of patients. These results did not support the role of adrenomedullin as an independent survival factor for lung cancer. However, AM inhibition in conjunction with other anti-angiogenic agents may be useful in the prevention and treatment of malignancies.