肺鳞状细胞癌组织中p63、CK5/6和p40的表达及其病理诊断价值

目的:探讨p63蛋白、细胞角蛋白5/6（cytokeratin5/6,CK5/6）和p40（ΔNp63）蛋白在人非小细胞肺癌（non-small cell lung cancer,NSCLC）组织中的表达及其表达对于肺鳞状细胞癌和肺腺癌的诊断和鉴别诊断价值。方法:采用免疫组化（SP法）检测p63、CK5/6和p40在100例病理确诊的NSCLC组织中的表达情况,并结合NSCLC的临床病理特征进行分析。结果:p63、CK5/6和p40在肺鳞状细胞癌组织中的阳性表达率分别为98.28%、100.00%和98.28%。p63、CK5/6和p40在肺腺癌组织中的阳性表达率分别为45.24%、30.95%和21.43%。肺鳞状细胞癌组织中p63、CK5/6和p40的阳性表达率明显高于肺腺癌组织（P<0.01）。p63、CK5/6和p40诊断肺鳞癌的灵敏度分别为98.28%、100.00%和98.28%,特异度分别为54.76%、69.05%和78.57%。p63、CK5/6和p40在肺鳞状细胞癌中的诊断准确率分别为80%、87%和90%。三者联合检测时三项均阳性诊断肺鳞癌的特异度达90.48%,诊断准确率为95%;三项中至少一项阳性诊断肺鳞癌的灵敏度达100.00%,诊断准确率为75%。结论:p63、CK5/6和p40主要表达在肺鳞状细胞癌组织中。单个指标中p40对诊断肺鳞状细胞癌具有较高的灵敏度和特异度。p63、CK5/6和p40联合检测对肺鳞状细胞癌与肺腺癌的鉴别诊断有重要价值。     

Loss of cytokeratin 13 expression in squamous cell carcinoma of the tongue is a possible sign for local recurrence

Cytokeratin (CK) 13 is an intermediate filament protein that is expressed in a cell-type-specific manner, in the tongue and occasionally in tongue squamous cell carcinoma (SCC). Correlations between the clinical features of patients with SCC and CK13 expression in the tumor are here investigated along with CK13's utility as a marker for tongue cancer status. Samples from 121 patients with SCC of the tongue were examined by immunohistochemistry with antibodies against CK13. Correlations between the expression level of CK13 in the tumor and the patients' clinical features were statistically analyzed by univariate and multivariate methods. Univariate analysis showed a more relevant number of local recurrence (P = 0.04) in CK13-negative staining patients. In addition, CK13-negative cases were associated with local recurrence by multiple logistic regression analysis (OR: 3.36; 95% CI: 1.044-10.78; P = 0.04). Our results suggest that the loss of CK13 expression indicates tumors with a high potential for recurrence, and thus CK13 could be useful for determining the best course of treatment.     

Locally advanced cervical carcinoma patients treated with chemoradiation followed by radical surgery: clinical response and oncological outcomes according to histotype after propensity score analysis

IntroductionThe aims of this study were to analyze the pathological response, and survival outcomes of adenocarcinoma/adenosquamous (AC/ASC) versus squamous cell carcinoma (SCC) in patients with locally advanced cervical cancer (LACC) managed by chemoradiotherapy followed by radical surgery.MethodsRetrospective, multicenter, observational study, including patients with SCC and AC/ACS LACC patients treated with preoperative CT/RT followed by tailored radical surgery (RS) between 06/2002 and 05/2017. Clinical-pathological characteristics were compared between patients with SCC versus AC/ASC. A 1:3 ratio propensity score (PS) matching was applied to remove the variables imbalance between the two groups.ResultsAfter PS, 320 patients were included, of which 240 (75.0%) in the SCC group, and 80 (25.0%) in the AC/ASC group. Clinico-pathological and surgical baseline characteristics were balanced between the two study groups. Percentage of pathologic complete response was 47.5% in SCC patients versus 22.4% of AC/ASC ones (p < 0.001). With a median follow-up of 51 months (range:1–199), there were 54/240 (22.5%) recurrences in SCC versus 28/80 (35.0%) in AC/ASC patients (p = 0.027). AC/ASC patients experienced worse disease free (DFS), and overall survival (OS) compared to SCC patients (p = 0.019, and p = 0.048, respectively). In multivariate analysis, AC/ACS histotype, and FIGO stage were associated with worse DFS and OS.ConclusionIn LACC patients treated with CT/RT followed by RS, AC/ASC histology was associated with lower pathological complete response to CT/RT, and higher risk of recurrence and death compared with SCC patients. This highlights the need for specific therapeutic strategies based on molecular characterization to identify targets and develop novel treatments.     

Involvement of VILIP-1 (visinin-like protein) and opposite roles of cyclic AMP and GMP signaling in in vitro cell migration of murine skin squamous cell carcinoma

VILIP-1 (visinin-like protein 1) is downregulated in various human squamous cell carcinoma (SCC). In a mouse skin SCC model VILIP-1 expression is reduced in aggressive tumor cells, accompanied by reduced cAMP levels. Overexpression of VILIP-1 in aggressive SCC cells led to enhanced cAMP production, in turn causing a reduction in invasive properties. Moreover, in primary neurons and neuronal tumor lines VILIP-1 enhanced cGMP signaling. Here, we set out to determine whether and how cAMP and cGMP signaling contribute to the VILIP-1 effect on enhanced SCC model cell migration, and thus most likely invasiveness in vivo. We found stronger increase in cGMP levels in aggressive, VILIP-1-negative SCC cells following stimulation of guanylyl cyclases NPR-A and -B with the natriuretic peptides ANP and CNP, respectively. Incubation with ANP or 8Br-cGMP to increase cGMP levels further enhanced the migration capacity of aggressive cells, whereas cell adhesion was unaffected. Increased cGMP was caused by elevated expression levels of NPR-A and -B. However, the expression level of VILIP-1 did not affect cGMP signaling and guanylyl cyclase expression in SCC. In contrast, VILIP-1 led to reduced migration of aggressive SCC cells depending on cAMP levels as shown by use of adenylyl cyclase (AC) inhibitor 2',3'-dideoxyadenosine. Involvement of cAMP-effectors PKA and EPAC play a role downstream of AC activation. VILIP-1-positive and -negative cells did not differ in mRNA expression of ACs, but an effect on enhanced protein expression and membrane localization of ACs was shown to underlie enhancement of cAMP production and, thus, reduction in cell migration by VILIP-1.     

成束蛋白和细胞角蛋白14在多种肿瘤组织中的表达及其鉴别诊断意义

目的 揭示成束蛋白(fascin)和细胞角蛋白14(CK14)在不同器官的相同或不同组织学类型癌组织中的表达规律,探讨其鉴别诊断的应用价值.方法 构建450例不同器官的相同或不同组织学类型癌组织芯片,用免疫组化方法检测fascin和CK14的表达情况.结果 fascin在食管、肺、喉、宫颈和外生殖器的鳞癌中弥漫高表达,阳性率分别为90.0%、90.0%、96.7%、78.6%和89.7%,在肺腺癌、胃腺癌、结直肠腺癌、肝细胞癌、胰腺导管腺癌、乳腺浸润性导管癌、甲状腺乳头状癌、子宫宫内膜样腺癌、卵巢浆液性囊腺癌和肾透明细胞癌中表达阳性率分别为38.0%、23.3%、14.3%、10.3%、73.3%、13.3%、6.7%、60.0%、66.7%和10.0%;在鳞癌和其他组织学类型肿瘤中的表达差异有统计学意义(P＜0.001).CK14在食管、肺、喉、宫颈和外生殖器鳞癌中表达阳性率分别为76.7%、36.7%、83.3%、60.7%和96.3%,而在肺腺癌、胃腺癌、结直肠腺癌、肝细胞癌、胰腺导管腺癌、乳腺浸润性导管癌、甲状腺乳头状癌、子宫宫内膜样腺癌、卵巢浆液性囊腺癌和肾透明细胞癌中表达阳性率分别为13.3%、13.3%、20.7%、41.4%、46.7%、6.7%、40.0%、13.3%、20.0%和6.7%;在鳞癌和其他组织学类型肿瘤中的表达差异有统计学意义(P＜0.001).fascin与CK14联合,在鳞癌中任一蛋白阳性率,与在其他组织学类型肿瘤中的表达差异均有统计学意义(P＜0.001).结论 fascin和CK14在多器官鳞癌呈高表达,在其他组织学类型肿瘤呈较低表达.联合检测fascin和CK14的表达,可用于鳞癌的诊断和鉴别诊断.     

EphB1 and Ephrin-B,New Potential Biomarkers for Squamous Cell/adenosquamous Carcinomas and Adenocarcinomas of the Gallbladder

Squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder are rare tumors and there arefew clinical reports in the literature. Herein we report our clinical experience with 46 patients with SC/ASCand 80 with adenocarcinoma (AC). Expression of EphB1 and Ephrin-B in each tumor was determined usingimmunohistochemical methods for determination of correlations with prognosis. There was no difference in EphB1and Ephrin-B expression between SC/ASC and AC tumors (P>0.05), but greater expression in those less than3 cm in diameter, stage Ⅰ or Ⅱ (TNM stage), with no lymph node metastases, with no local invasion and treatedwith radical resection was apparent. Expression of EphB1 (P<0.05) and Ephrin-B (P<0.01) was higher in welldifferentiated than in poorly differentiated AC tumors. Kaplan-Meier survival analysis indicated that degreeof differentiation, tumor diameter, lymph node metastases, local invasion, surgical approach and expressionrate of EphB1 and Ephrin-B were closely related to the survival of SC/ASC (P<0.05) and AC patients (P<0.01).Patients with tumors that positive expressed EphB1 and Ephrin-B, whether it is SC/ASC (P SC/ASC =0.000) orAC (P AC =0.000 or P AC =0.002) had longer survival than those negative expression. Cox multivariate analysisindicated a negative correlation between expression of EphB1 or Ephrin-B and overall survival. Hence, EphB1and Ephrin-B could be regarded as independent good prognostic factorsand important biological markers forSC/ASC and AC of gallbladder.     

Adenosquamous carcinoma of the esophagus. Clinicopathologic study of 18 cases

OBJECTIVES: Adenosquamous carcinoma (ASC) of the esophagus is an uncommon form of esophageal cancer. Despite isolated case reports on this tumor type, no large clinicopathologic series appears to have been studied at a single institution. METHODS: At our institution, 20 cases of ASC were diagnosed pathologically between 1970 and 2001 (20/2,056 total esophageal cancers; 1.0%). Excluding 2 patients who received preoperative radiation therapy, 18 were selected for review of their clinicopathologic features, including survival time, in comparison with those of patients with conventional squamous cell carcinomas (SCCs; n = 850) and adenocarcinomas (ACs; n = 40) of the esophagus. RESULTS: The location and macroscopic type of the ASCs were similar to those of the SCCs. ASC tumors were significantly smaller than SCC (p = 0.004) and AC (p = 0.012) tumors, and the depth of invasion of ASCs was significantly less than that of SCCs (p = 0.028). Lymphatic permeation and blood vessel invasion were seen in 14 (77.8%) and 7 (38.9%) of the 18 patients with ASCs, respectively, and intraepithelial carcinoma contiguous to the main lesion was evident in 10 cases (56.6%). The cumulative postoperative survival rates of patients with ASC at 3, 5 and 10 years were 71.5, 63.6 and 47.7%, respectively, the outcome being significantly better than for patients with either SCC (p = 0.027) or AC (p = 0.013). CONCLUSION: In the esophagus, ASCs have better prognosis than conventional SCCs or ACs, probably due to their smaller size and lower stage.     

皮肤鳞癌中 DBPA mRNA 的表达及其与表皮分化的关系

目的：DNA结合蛋白（DBPA）又称为ZO-1相关核苷酸结合蛋白（ZONAB）,有很重要的转录活性,ZONAB可与ZO-1相结合,并通过抑制G1～S期的转化来调节上皮的增殖。本文研究DBPA在皮肤鳞癌中的作用机制及其与角质形成细胞异常分化的关系。方法：用原位杂交的方法检测正常皮肤组织、未受累组织及鳞癌皮损中DBPAmRNA的表达变化。结果：DBPAmRNA强表达于正常组织表皮颗粒层,弱表达于棘层上部;在未受累组织中强表达于颗粒层及棘层上部;在鳞癌中,DBPA可表达于绝大多数的肿瘤细胞。正常组织和未受累组织中DBPA的表达均与鳞癌皮损中的表达有显著差异性（P〈0．01）。结论：DBPA可能参与鳞癌的角质形成细胞的分化和增殖。     

连接蛋白43、Kai1和PTEN蛋白在皮肤基底细胞癌中的表达及意义

 目的 探讨皮肤基底细胞癌（basal cell carcinoma,BCC）发生发展及其特殊生物学行为的相关因素。方法 免疫组织化学SP法分别检测35例皮肤BCC、10例正常皮肤和18例皮肤鳞状细胞癌（squamous cell cacinoma,SCC）组织中Cx43、Kai1、PTEN蛋白的表达;核酸分子原位杂交法检测Cx43 mRNA的表达。应用计算机图像分析系统分别检测各组中各种检测指标的阳性面积和表达强度; SPSS（13.0）软件包进行统计分析。结果 （1）Cx43蛋白、Cx43 mRNA在皮肤表皮中的表达呈强阳性,在BCC组呈阳性或弱阳性,在SCC组呈阴性或弱阳性。Cx43及其 mRNA在BCC组的表达与正常皮肤组及SCC组比较,差异均有统计学意义（P<0.01）。（2）Kai1、PTEN蛋白在皮肤表皮中的表达呈强阳性,在BCC组呈阳性或弱阳性,在SCC组呈阴性或弱阳性。Kai1、PTEN蛋白在BCC组的表达与正常皮肤组及SCC组比较,差异均有统计学意义（P<0.05）。（3）相关分析显示,BCC组织中,PTEN蛋白的表达与Kai1蛋白呈正相关(r=0.629,P<0.01),与Cx43蛋白(r=0.519,P＜0.01)也呈正相关;Cx43蛋白的表达与Cx43 mRNA呈正相关(r=0.732,P<0.01)。结论 （1）与正常皮肤组织比较,BCC中Cx43、Kai1、PTEN蛋白和Cx43mRNA低表达,可能在BCC发生发展的过程中发挥重要作用;（2）与SCC组织相比较,BCC中Cx43、Kai1、PTEN蛋白和Cx43mRNA高表达,可能与BCC生长缓慢及极少转移的生物学特性有关。     

Expression of mRNA of SCC antigen in squamous cells.

The expression of SCC antigen mRNA was studied by Northern blot analysis and in situ hybridization in human gynecologic tissues. Northern blot analysis revealed that mRNA of SCC antigen was expressed strongly in normal squamous epithelium and columnar epithelium of the uterine cervix, but not in the endometrium, fallopian tube or ovarian tissue. Among gynecologic malignancies, squamous cell carcinoma of the uterine cervix expressed mRNA of SCC antigen, whereas endometrial and ovarian adenocarcinoma were negative. With in situ hybridization, mRNA of SCC antigen is located in the basal and parabasal layers of the normal squamous epithelium, in dysplasia, and also in carcinoma in situ and invasive squamous cell carcinoma. These results confirmed the previous findings by immunohistochemical studies that SCC antigen is closely related to squamous cells, but also raised a new puzzle regarding the different localization of mRNA and its product, SCC antigen, in the normal squamous epithelium.     

Elevation of cyclooxygenase-2 is related to lymph node metastasis in adenocarcinoma of uterine cervix

In a previous study, we demonstrated that elevation of COX-2 is significantly associated with lymph node metastasis in squamous cell carcinoma (SCC) of cervix. The main objective of this study is to characterize the relationship between elevation of COX-2 and its possible clinical role in adenocarcinoma (AC) of cervix. Using immunohistochemistry, we examined COX-2 expression levels in 84 patients with AC of uterine cervix [71 ACs, 13 adenosquamous carcinomas (ASCs)]. Elevation of COX-2 was correlated with clinicopathological variables and p53 expression, as detected by immunohistochemistry. Elevation of COX-2 was detected in 13.0% (11 of 84) of the tumors. Elevation of COX-2 was significantly correlated with histologic type (AC 8.5% vs. ASC 38.5%, P=0.011). Both tumor stage and lymph node metastasis were correlated with elevation of COX-2 with a borderline significance (P=0.062 and 0.068, respectively). Elevation of p53 was not associated with elevation of COX-2. The association between lymph node metastasis and elevation of COX-2 was stronger in cases of AC than in cases of ASC (28.4 vs. 4.3%, P=0.023). According to the results of univariate analysis, elevation of COX-2 was significantly associated with decreased overall survival (P=0.003, log-rank test). However, multivariate analyses revealed that only tumor stage was independently associated with overall survival, suggesting that elevation of COX-2 itself may not be an independent prognostic factor. The present study shows that elevation of COX-2 may contribute to lymph node metastasis in AC of uterine cervix. This suggests that the potential therapeutic role of COX-2 inhibitors should be validated, not only in SCC, but also in AC of uterine cervix.     

Detection of tumor-specific autoantibodies in sera of patients with lung cancer

The presence of autoantibodies (AAs) in sera from two pulmonary carcinoma patients, adenocarcinoma (AD) and small cell carcinoma (SCLC) was screened by immunoblotting using cell lysate of four cell lines (LCN1, large cell neuroendocrine carcinoma (LCNEC); N231, SCLC; A549, AD; RERF-LC-AI, squamous cell carcinoma (SCC)). To identify the antigens recognized by AAs, two-dimensional gel electrophoresis was immunoblotted and target spots were cut out from the membrane and gel. After trypsin digestion, the proteins were analyzed by mass-spectrometry using a liquid chromatography-tandem mass spectrometer. By this method, cytokeratin18 (CK18) and villin1 were identified with AAs in sera from patients with AD and SCLC, respectively. Thus, the expressions of CK18 and villin1 were further immunohistochemically studied on 124 formalin-fixed and paraffin-embedded pulmonary carcinomas of various histologic types (44 AD, 27 SCC, 29 SCLC, and 34 LCNEC) using commercially available CK18 and villin1 antibodies. Positive CK18 immunostaining was observed in almost all cases with staining intensities significantly higher in AD and LCNEC than in SCC and SCLC. Villin1 was detected in 17/44 (38.6%) of AD and 21/34 (61.8%) of LCNEC, respectively, while in only one each of SCLC and SCC. Thus, villin1 and CK18 may be useful markers to distinguish LCNEC/AD from SCLC/SCC, and the present method might be useful to identify specific tumor-associated molecules in sera from pulmonary carcinoma patients with different histologic types.     

Expression of simple epithelial cytokeratins in mouse epidermal keratinocytes harboring Harvey ras gene alterations.

Activation of a Harvey ras (H-ras) protooncogene is a frequent event associated with mouse epidermal carcinogenesis. We report that the transfection of a human H-ras oncogene into an immortalized mouse epidermal cell line (MCA3D) induces the anomalous expression of cytokeratins (CKs) 8 and 18 characteristic of simple epithelia. The comparison of various transfectant cell clones indicated a direct correlation between the levels of CK8 expression and the mutated H-ras p21s. The expression of simple epithelial CKs is also described in cell lines derived from mouse skin carcinomas (HaCa4, CarC) and in keratinocytes transformed in vitro by a chemical carcinogen (PDV, PDVC57), all of which contain altered H-ras genes. The induction of CK8 and CK18 occurs at the mRNA level and, although both CK8 and CK18 mRNAs are expressed, CK18 protein does not accumulate whereas CK8 is incorporated into intermediate filaments. Immunofluorescence studies show that the pattern of CK8 protein expression is heterogeneous; some cells express very low amounts of CK8, whereas others synthesize relatively high levels of this protein. However, selection of strongly CK8-positive cells was found in one case where a more malignant population of cells (PDVC57) was derived by tumor transplantation of PDV. Our results suggest that activation of a H-ras gene can alter the normal differentiation program of epidermal cells and that the ability to synthesize CK8 and CK18 could be related to tumor progression.     

BRAK/CXCL14 is a potent inhibitor of angiogenesis and a chemotactic factor for immature dendritic cells

BRAK/CXCL14 is a CXC chemokine constitutively expressed at the mRNA level in certain normal tissues but absent from many established tumor cell lines and human cancers. Although multiple investigators cloned BRAK, little is known regarding the physiologic function of BRAK or the reason for decreased expression in cancer. To understand the possible significance associated with loss of BRAK mRNA in tumors, we examined the pattern of BRAK protein expression in normal and tumor specimens from patients with squamous cell carcinoma (SCC) of the tongue and used recombinant BRAK (rBRAK) to investigate potential biological functions. Using a peptide-specific antiserum, abundant expression of BRAK protein was found in suprabasal layers of normal tongue mucosa but consistently was absent in tongue SCC. Consistent with previous in situ mRNA studies, BRAK protein also was expressed strongly by stromal cells adjacent to tumors. In the rat corneal micropocket assay, BRAK was a potent inhibitor of in vivo angiogenesis stimulated by multiple angiogenic factors, including interleukin 8, basic fibroblast growth factor, and vascular endothelial growth factor. In vitro, rBRAK blocked endothelial cell chemotaxis at concentrations as low as 1 nmol/L, suggesting this was a major mechanism for angiogenesis inhibition. Although only low affinity receptors for BRAK could be found on endothelial cells, human immature monocyte-derived dendritic cells (iDCs) bound rBRAK with high affinity (i.e., K(d), approximately 2 nmol/L). Furthermore, rBRAK was chemotactic for iDCs at concentrations ranging from 1 to 10 nmol/L. Our findings support a hypothesis that loss of BRAK expression from tumors may facilitate neovascularization and possibly contributes to immunologic escape.     

Complexity of expression of the intermediate filaments of six new human ovarian carcinoma cell lines: new expression of cytokeratin 20.

Six permanent human ovarian carcinoma cell lines (OVISE, OVTOKO, OVMANA and OVSAYO from clear cell adenocarcinoma, and OVSAHO and OVKATE from serous papillary adenocarcinoma) were established from solid tumours. The cell lines have been in culture for 5-8 years, the passage number varying from 62 to 246. Immunohistochemical analysis has shown that five of the six cell lines express at least six cytokeratin (CK) polypeptides. OVISE and OVSAYO expressed CKs 6, 7, 8, 18, 19 and 15 and/or 16. OVTOKO was positive for CKs 7, 8, 18, 19 and 15 and/or 16. OVSAHO expressed CKs 6, 7, 8, 14, 18, 19 and 15 and/or 16. OVMANA expressed CKs 6, 7, 8, 18, 19, 20 and 15 and/or 16. OVKATE expressed CKs 6, 7, 8, 13, 17, 18, 19, 20 and 15 and/or 16. The expression of CK7, additional expression of vimentin, and clinical and histopathological findings enabled us to confirm that six cell lines had been established from primary ovarian cancers. Two of the six cell lines were positive for CK20, although CK20 was not expressed in the original tumours. The heterotransplanted tumours produced by CK20-positive cells also expressed CK20. This is the first report of ovarian carcinoma cell lines that express CK20 irrespective of their histological type. CK20 has been found in all colon carcinoma cell lines, but only in the mucinous type of ovarian tumours. These new ovarian carcinoma cell lines will therefore provide a relevant experimental system for elucidating the regulatory control mechanisms of intermediate filament expression.     

宫颈癌活检病理与术后石蜡病理的符合率及意义

目的:探讨宫颈癌术前阴道镜下宫颈活检病理与子宫全切或广切术后石蜡病理的符合率及其临床意义.方法:回顾性分析2012年1月-2015年5月就诊于中国医科大学附属盛京医院妇科行手术治疗的1 872例宫颈恶性肿瘤患者的临床病理资料.对符合纳入标准的1 818例患者进行统计研究.结果:1 818例患者中,宫颈鳞状细胞癌1 575例,宫颈腺癌173例,宫颈腺鳞癌53例,其他病理类型17例.1 818例患者中,宫颈活检病理与子宫全切或广切术后石蜡病理结果相符合的为1 487例,总符合率为81.8%.其中816例直接于我院行宫颈活检及病理组织检查,1 002例于外院行宫颈活检后于我院行病理切片会诊,我院宫颈活检病理诊断符合率为83.8%,外院为80.1%,差异有统计学意义.我院宫颈鳞癌、腺癌、腺鳞癌及其他少见病理类型诊断符合率为86.7%、75.3%、40.7%、70.0%;外院宫颈鳞癌、腺癌、腺鳞癌及其他少见病理类型诊断符合率为82.0%、80.4%、26.9%、42.9%,宫颈鳞癌诊断符合率两者之间差异有统计学意义.外院与我院高-中分化组宫颈癌的活检病理诊断符合率均明显高于低分化组,差异有统计学意义.原位癌-Ia1期宫颈癌的宫颈活检病理诊断符合率均明显低于Ia2期-IIb期,差异有统计学意义.结论:阴道镜下宫颈活检有漏诊宫颈癌的可能,尤其是原位癌-Ia1期宫颈癌;完善上级医院病理会诊可提高术前诊断的准确性,对于临床上治疗方案的选择具有重要价值.     

Expression of cell proliferating genes in patients with non-small cell lung cancer by immunohistochemistry and cDNA profiling

Thymidine kinase 1 (TK1) is a key enzyme involved in the synthesis of DNA precursors and thus, cell proliferation-dependent. Antibodies against TK1 have provided attractive tools for cancer diagnosis. Expression of TK1 in 158 non-small cell lung cancer (NSCLC) patients with 59 adenocarcinoma (AC) and 99 squamous cell carcinoma (SCC) was determined by anti-TK1 monoclonal antibody (mAb) 1E3 (AC, n=50; SCC, n=70). Parallel tumor sections were stained for Ki-67 (MIB-1), and TK1 expression was also investigated with anti-TK1 chicken IgY Ab (AC, n=9; SCC, n=29; normal lung tissues, n=10). In one AC and one SCC patient, gene profiling was done by cDNA array. Using the mAb 1E3, a significantly higher TK1 labeling index (LI) of AC patients was found (68%) compared to the LI of Ki-67 (36%). This difference was due to a significantly higher TK1 LI of tumor stage II and grade 2. Although no difference in the LI of TK1 and Ki-67 of SCC patients was found (54 vs. 53%), significantly higher TK1 LI of SCC patients of tumor grade 1 was found. Using the anti-TK1 IgY Ab, a higher TK1 LI of AC patients (78%) and SCC patients (66%) was found compared to staining with mAb 1E3 (68 vs. 54%), but it was not significantly different. Samples stained only for TK1 represented mostly tumor stages I and II and grades 1 and 2 of both AC and SCC. AC patients whose samples stained only for Ki-67 were found to be in stage I and grade 1. cDNA profiling showed that the expression of BRCA1, cyclin B1 and cdc2p34 was higher in AC compared to SCC, while the expression of IGFBP-3 and EGFR was higher in SCC. TK1 is apparently a more reliable marker in AC patients than Ki-67. However, a combination of the two markers may help identify patients of different stages and grades more efficiently, and cyclin/kinase complexes and growth factors/receptors may be useful markers in distinguishing AC from SCC.     

Differences in clinicopathological and biological features between central-type and peripheral-type squamous cell carcinoma of the lung

The central type and peripheral type squamous cell carcinoma (SCC) of the lung have different clinicopathological characteristics, but, little is known about their biological characteristics. We investigated differences between the properties and phenotypes of peripheral-type (P-type) and central-type (C-type) SCC by performing an immunohistochemical analysis of each type by tissue microarray analysis with a large panel of antibodies. To examine strictly, we selected 20 P-type SCCs that were pathological stage T1 and limited to more peripherally than the fifth bronchial bifurcation, and 21 C-type SCCs that were pathological stage T1 and limited to a lobar bronchus. The results of the clinicopathological study showed that the patients with P-type SCC were significantly older than the patients with C-type SCC and that squamous metaplasia was predominant in C-type SCC than in P-type SCC. The 36 antibodies revealed different expression patterns of cytokeratin 7 (CK 7) and cytokeratin 19 (CK 19) between C-type and P-type SCC. CK 7 expression was more predominant in P-type SCC than in C-type SCC, and CK 19 expression was more predominant in C-type SCC than in P-type SCC. These results suggest that C-type and P-type SCC have different clinicopathological and biological features.