甲状腺未分化癌组织vWF表达与血管生成拟态相关性研究

目的 肿瘤源性的血管性血友病因子(von Willbrend factor,vWF)表达及血管生成拟态(vasculogenic mimicry,VM)形成都是高度恶性肿瘤中的高频事件.本研究检测甲状腺未分化癌组织中vWF的表达及VM水平,在组织学水平上探讨vWF的表达及其与肿瘤组织中VM形成的相关性.方法 选取甘肃省人民医院(20例)及甘肃省肿瘤医院(43例)2000-01-01-2014-12-31病理诊断为甲状腺未分化癌的手术标本63例.同时随机挑选甘肃省人民医院同期甲状腺乳头状癌病例63例和相应癌旁正常组织作为对照.采用免疫组化法检测甲状腺组织中vWF蛋白的表达水平,CD31联合PAS双重染色检测VM水平.结果 vWF蛋白在正常甲状腺组织无表达,甲状腺乳头状癌中有5例(7.90%)阳性表达,甲状腺未分化癌中vWF阳性表达31例(49.20%),组间比较差异有统计学意义,χ2=26.289,P<0.001.vWF在甲状腺未分化癌中的阳性表达与患者的性别、年龄、肿瘤大小和淋巴结转移无关,而与远处转移(χ2=5.341,P=0.021)和临床分期(χ2=4.753,P=0.029)相关.VM在正常甲状腺组织、乳头状癌及甲状腺未分化癌中的形成率分别为0、3.20%和34.92%,组间差异有统计学意义,χ2=20.588,P<0.001.VM形成与肿瘤最大径(χ2=4.789,P=0.029)、淋巴结转移(χ2=5.684,P=0.028)、远处转移(χ2=4.722,P=0.030)和临床分期(χ2=5.777,P=0.061)相关.vWF的表达与VM水平正相关,r=0.411,P=0.001.结论 甲状腺未分化癌中有不同程度vWF的高表达,其高表达与VM的形成正相关,vWF的高表达可能是导致甲状腺未分化癌预后差的因素之一.     

Utilization and impact of adjuvant therapy in anaplastic oligodendroglioma: an analysis on 1692 patients

The aim of this study was to determine the utilization rates and impact of adjuvant therapy on overall survival (OS) for anaplastic oligodendroglioma (AO). Data were extracted from the National Cancer Data Base (NCDB). Chi square test, Kaplan–Meier method, and Cox regression models were employed in SPSS 22.0 (Armonk, NY: IBM Corp.) for data analyses. 1692 patients with AO who underwent surgery were identified. 945 (55.9?%) received adjuvant radiotherapy with concomitant chemotherapy (chemoRT), 102 (6.0?%) adjuvant radiotherapy (RT) sequentially followed by chemotherapy, 244 (14.4?%) adjuvant RT alone, and 401 (23.7?%) received no adjuvant therapy. Patients were more likely to receive adjuvant chemoRT if they were diagnosed in 2009-2013 vs. 2004–2008 (p?70 vs. <70 (p?=?0.018), had private insurance vs. Medicaid vs. no insurance (p?相似文献   

Number of glioma polyploid giant cancer cells (PGCCs) associated with vasculogenic mimicry formation and tumor grade in human glioma

Background

Polyploid giant cancer cells (PGCCs) contribute to solid tumor heterogeneity. This study investigated the relationships among PGCCs numbers, vasculogenic mimicry (VM) formation, and tumor grades in glioma.

Methods

A total of 76 paraffin-embedded glioma tissue samples, including 28 cases of low grade and 48 cases of high grade gliomas, were performed with H&E and immunohistochemical staining for Ki-67 and hemoglobin. The size of PGCCs nuclei was measured by a micrometer using H&E section and defined as at least three times larger than the nuclei of regular diploid cancer cells. The number of PGCCs and different blood supply patterns were compared in different grade gliomas. Microcirculation patterns in tumors were assessed using CD31 immunohistochemical and PAS histochemical double staining. Human glioma cancer cell line C6 was injected into the chicken embryonating eggs to form xenografts, which was used to observe the PGCCs and microcirculation patterns.

Results

In human glioma, the number of PGCCs increased with the grade of tumors (χ² = 4.781, P = 0.015). There were three kinds of microcirculation pattern in human glioma including VM, mosaic vessel (MV) and endothelium dependent vessel. PGCCs were able to generate erythrocytes via budding to form VM. The walls of VM were positive (or negative) for PAS staining and negative for CD31 staining. There were more VM and MVs in high grade gliomas than those in low grade gliomas. The differences have statistical significances for VM (t = 3.745, P = 0.000) and MVs (t = 4.789, P = 0.000). PGCCs, VM and MVs can also be observed in C6 chicken embryonating eggs xenografts.

Conclusions

The data demonstrated presence of PGCCs, VM and MVs in glioma and PGCCs generating erythrocytes contribute the formation of VM and MVs.     

Methylation of multiple genes in prostate cancer and the relationship with clinicopathological features of disease

Promoter methylation plays an important role in the inactivation of tumor suppressor genes during tumorigenesis. We examined the methylation status of glutathione s-transferase Pi1 (GSTP1), retinoic acid receptor beta (RARB), CD44, E-cadherin (ECAD), RAS association domain family protein 1A (RASSF1A) and endothelin B receptor (EDNRB) genes in 81 prostate cancer and 42 benign prostatic hyperpasia specimens. Genomic DNA was isolated from archived formaldehyde-fixed and paraffin-embedded tissue blocks. Methylation-specific PCR (MSP) was carried out after bisulfite treatment of genomic DNA. Methylation frequencies in prostate cancer and benign prostatic hyperplasia were 72% and 5% for GSTP1, 40% and 0% for RARB, 72% and 38% for CD44, 61% and 14% for ECAD, 49% and 19% for RASSF1A and 72% and 62% for EDNRB, respectively. Methylation of GSTP1, RARB, CD44, ECAD and RASSF1A, but not of EDNRB was detected at a statistically higher frequency in prostate cancer than in the benign prostatic hypertrophy specimens. Methylation of RARB occurred more frequently in early onset (age <55 years) as compared to late onset disease (age >70 years) (odds ratio, 8.6; 95% CI, 1.4-51.4; P=0.02). Methylation of RARB also occurred more frequently in stage III as compared to stage II disease (odds ratio, 3.2; 95% CI, 1.1-8.8; P=0.03). A methylation index (MI) was calculated as the total number of genes methylated, excluding EDNRB. A trend toward higher MI was noted in stage III as compared to stage II disease, and in Gleason score 7 as compared to Gleason score 6 tumors. Our results suggest that the methylation of selected genes in prostate cancers correlates with clinicopathological features of poor prognosis.     

Molecular regulation of tumor cell vasculogenic mimicry by tyrosine phosphorylation: role of epithelial cell kinase (Eck/EphA2)

During embryogenesis, blood vessels are formed initially by the process of vasculogenesis, the in situ differentiation of mesenchymal cells into endothelial cells, which form a primitive, patterned vasculogenic network. This is followed by angiogenesis, the sprouting of new vessels from preexisting vasculature, to yield a more refined microcirculation. However, we and our collaborators have recently described a process termed "vasculogenic mimicry," which consists of the formation of patterned, tubular networks by aggressive melanoma tumor cells (in three-dimensional cultures in vitro), that mimics endothelial-formed vasculogenic networks and correlates with poor clinical prognosis in patients. Previous microarray analysis from our laboratory comparing the highly aggressive versus the poorly aggressive melanoma cells revealed a significant increased expression of tyrosine kinases associated with the aggressive melanoma phenotype. Because of the important role of protein tyrosine kinases in phosphorylating various signal transduction proteins that are critical for many cellular processes (e.g., cell adhesion, migration, and invasion), we examined whether protein tyrosine kinases are involved in melanoma vasculogenic mimicry. Immunofluorescence analysis of aggressive melanoma cells forming tubular networks in vitro showed that tyrosine phosphorylation activity colocalized specifically within areas of tubular network formation. A phosphotyrosine profile of the aggressive melanoma cells capable of forming tubular networks indicated differences in tyrosine phosphorylated proteins compared with the poorly aggressive melanoma cells (incapable of forming tubular networks). Most notably, we identified epithelial cell kinase (EphA2) as being one receptor tyrosine kinase expressed and phosphorylated exclusively in the aggressive metastatic melanoma cells. Furthermore, general inhibitors of protein tyrosine kinases hindered tube formation, and transient knockout of EphA2 abrogated the ability of tumor cells to form tubular structures. These results suggest that protein tyrosine kinases, particularly EphA2, are involved in the formation of tubular networks by aggressive melanoma tumor cells in vitro, which may represent a novel therapeutic target for further clinical investigation.     

Genomic aberrations in anaplastic multiple myeloma: High frequency of 1q21(CKS1B) amplifications

Anaplastic multiple myeloma (AMM) is a rare morphologic variant of MM with adverse prognosis. The underlying molecular cytogenetic abnormalities are poorly understood. We investigated 11 patients with AMM for myeloma associated cytogenetic aberrations and compared with 188 non-anaplastic MM using fluorescent in situ hybridization. Of the 11 AMM patients studied, 10 had CKS1B amplification, 5 hemizygous 17p(p53) deletions, 4 13q14 deletions, 4 t(4:14), and 2 had t(11:14). AMM was associated with significantly higher prevalence of CKS1B amplification (91% vs. 34%, p < 0.001), 17p(p53) deletion (45% vs. 11%, p = 0.006) and t(4,14) (36% vs. 14%, p = 0.015) than non-anaplastic MM, which may have resulted in the genetic instability and more aggressive clinical course.     

Evaluation of P-glycoprotein expression in human oral oncogenesis: Correlation with clinicopathological features

To determine whether the multidrug-resistance-gene product phospho-glycoprotein (P-gp) is implicated in progression of oral tumours and/or drug resistance, the expression of P-gp was examined in different stages of oral oncogenesis using monoclonal antibody C-219. Cryosections from normal (41 cases), dysplastic lesions (32 cases), untreated primary SCCs (50 cases) and recurrent tumours (31 cases) were used for immunostaining, and the results were corroborated by immunoblotting. Chi-square test for trend analysis showed a significant increase in P-gp immunopositivity across the normal, leukoplakia, primary oral SCC and recurrent SCC groups (p < 0.01). Expression of P-gp in dysplastic lesions showed significant association with severity of dysplasia, the level of P-gp protein being higher in severe and moderate dysplasia. Among the primary tumours, significant correlation was observed between P-gp positivity as well as level of P-gp expression and tumour stage. The recurrent tumours showed significant increase in P-gp expression as compared with untreated primary oral tumours. We conclude that differential expression of P-gp may be an index of the disease prognosis in oral-cancer patients in the context of the Indian population. Int. J. Cancer 72:728–734, 1997. © 1997 Wiley-Liss, Inc.     

近端型与远端型细支气管腺瘤临床病理特征的比较分析（附4例）

目的:探讨细支气管腺瘤（BA）的两型临床病理特征、诊断及鉴别诊断。 方法:收集该院2018年3月至2021年4月收治的4例BA病例,分析其临床资料、影像学检查、组织病理学特征、免疫组织化学表型及鉴别诊断等。 结果:患者中男性2例,女性2例,1例有吸烟史,2例无临床症状。影像学表现为磨玻璃或边界清楚的结节。大体示灰白、灰褐色的实性结节或局灶见微囊,多数界清但无包膜,最大径0.6~1.2 cm。例1、例2肿瘤镜下显示双层乳头结构,内层富于纤毛细胞和黏液细胞,表达CK7、Napsin-A、CEA、MUC5AC,弱表达TTF-1,外层是基底细胞,表达p40、CK5/6,诊断为近端型BA。例3、例4肿瘤镜下显示双层腺腔型结构,内层由Ⅱ型肺泡上皮和Clara细胞构成,缺乏纤毛和黏液细胞,表达CK7、Napsin-A、TTF-1、弱表达CEA、MUC5AC,外层由基底细胞构成,表达p40、CK5/6,诊断为远端型BA。 结论:细支气管腺瘤是一种具有双层结构的良性肿瘤,影像学检查及快速冷冻切片中易误诊为恶性。根据黏液细胞及纤毛细胞所占腔面细胞的比例,将细支气管腺瘤分为近端型和远端型。     

Overexpression of AQP5 in cervical cancer: correlation with clinicopathological features and prognosis

Accumulating evidence for overexpression of AQP5 in various types of human cancer suggests that it plays a key role in tumor biology. However, little is known about the function of AQP5 in human cervical cancer. This study was to investigate the expression profile of AQP5 in cervical cancer and its clinical significance. We detected the expression profile of AQP5 mRNA and protein in cervical cancer tissue and in corresponding normal tissue by qRT-PCR and western blotting. Immunohistochemistry was also used in the detection of AQP5 protein expression as well as the proliferation index of Ki-67. The clinicopathological implications of these proteins were analyzed statistically. Survival analysis was performed to assess prognostic significance. AQP5 mRNA was overexpressed in cervical cancer tissue when compared with corresponding normal tissue, so was AQP5 protein. Overexpression of AQP5 was significantly associated with lymph node involvement (P = 0.004). Overexpression of Ki-67 was associated with lymph node involvement (P = 0.018) and disease stage (P = 0.005). It was demonstrated a positive correlation between AQP5 and Ki-67 (r = 0.543, P < 0.01). Survival analysis revealed that overexpression of AQP5 and Ki-67 is associated with a poorer prognosis. These observations suggest that AQP5 plays a key role in cervical cancer and therefore may provide an opportunity for developing a novel therapeutic target as well as a prognostic marker in cervical cancer. Its evaluation with Ki-67 may provide reliable prognostic information on cervical cancer.     

Rapid accumulation and internalization of radiolabeled herceptin in an inflammatory breast cancer xenograft with vasculogenic mimicry predicted by the contrast-enhanced dynamic MRI with the macromolecular contrast agent G6-(1B4M-Gd)(256)

The rapid blood flow and perfusion of macromolecules in the inflammatory breast cancer xenograft (WIBC-9), which exhibits a "vasculogenic mimicry" type of angiogenesis without the participation of endothelial cells and expresses high levels of the HER-2/neu antigen, was evaluated in mice using 3D-micro-MR angiography using a novel macromolecular MR contrast agent [G6-(1B4M-Gd)(256)]. Herceptin, which recognizes the HER-2/neu antigen and has similar size (10 nm) to G6-(1B4M-Gd)(256), accumulated and internalized in the WIBC-9 tumors more quickly than in the control MC-5 tumors that progress with normal angiogenesis. Three dimensional micro-MRI with the G6-(1B4M-Gd)(256) macromolecular MRI contrast agent distinguishes between the different types of angiogenesis and is predictive of the rapid accumulation and internalization of Herceptin in the WIBC-9 inflammatory breast cancer xenograft.     

Diffuse gliomas in an adolescent with multiple enchondromatosis (Ollier's disease)

Ollier's disease is characterized by the hamartomatous proliferation of cartilage cells, producing masses termed chondromas. A patient presented with Ollier's disease which was found to be associated with diffuse gliomas. Investigating this disease is crucial as there is a high risk of sarcomatous transformation of the skeletal lesions as well as an increased risk of developing extra-osseous malignancies.     

叉头框转录因子M1在非小细胞肺癌中的表达及其与患者临床病理特征和生存的关系

目的 研究人非小细胞肺癌(NSCLC)组织中叉头框转录因子M1(FOXM1)蛋白的表达,探讨其与NSCLC临床病理参数及预后之间的关系.方法 应用免疫组化染色法检测68例NSCLC组织中FOXM1蛋白的表达水平.选取肿瘤组织6例(FOXM1蛋白阳性和阴性表达各3例)以及正常肺组织1例,采用Western blot法检测FOXM1蛋白的表达水平,以验证免疫组化检测结果.将免疫组化检测结果 与患者的临床病理特征及总生存时间(OS)进行统计学分析.结果 FOXM1蛋白的阳性表达产物定位于细胞质或细胞核,其在肿瘤组织中的阳性表达率为36.8%(25/68).Western blot法检测FOXM1蛋白的表达水平与免疫组化检测的结果 一致.FOXM1蛋白在进展期NSCLC中的阳性表达率显著高于早期NSCLC(P＝0.001).FOXM1蛋白阴性和阳性表达患者的中位OS分别为23.0和13.0个月(P＝0.001).单因素分析的结果 显示,NSCLC患者的预后与肿瘤的分化程度、淋巴结转移状态、分期以及FOXM1蛋白的表达情况相关(均P＜0.05).Cox比例风险回归模型分析的结果 显示,分期、淋巴结转移状态以及FOXM1蛋白的表达情况是NSCLC的独立预后因素(均P＜0.05).结论 FOXM1蛋白的表达情况是NSCLC的独立预后因素,与患者的预后呈负相关.

Abstract：

Objective To investigate the expression of forkhead box M1 (FOXM1) and its correlation with clinicopathological features and prognosis in patients with non-small cell lung cancer (NSCLC). Methods The expression of FOXM1 in 68 cases of NSCLC was detected by immunohistochemistry. The FOXM1 expression in 6 tumor tissues (3 cases with negative and 3 cases with positive expression of FOXM1) was analyzed by Western blotting to confirm the immunohistochemical results. The correlation of the expression of FOXM1 with clinicopathalogical features and overall survival of the NSCLC patients was analyzed. Results The expression of FOXM1 protein was detected in the nuclei or cytoplasms of the tumor cells. The positive expression rate of FOXM1 was 36.8% (25/68). Western blotting confirmed the immunohistochemical results. The expression level of FOXM1 in advanced stage cancer was significantly higher than that in early stage NSCLC (P=0.001). The median OS was 23.0 months in patients with negative expression of FOXM1 and 13.0 months in those with positive expression (P=0.001).Univariate analysis revealed that histological grade, lymph nodes status, TNM stage and FOXM1 expression were significantly associated with prognosis in the NSCLC patients (P<0.05). The Cox multivariate analysis demonstrated that lymph nodes status, TNM stage and FOXM1 expression were independent poor prognostic factors(P<0.05). Conclusion The expression status of FOXM1 in NSCLC is an independent prognostic factor and negatively correlated with prognosis.     

The treatment of multiple myeloma with docetaxel (an ECOG study)

BACKGROUND: Docetaxel has activity against multiple malignancies. In a previous ECOG study of untreated patients with multiple myeloma, paclitaxel was found to have mild activity, but had excessive toxicity. Docetaxel was evaluated in patients with relapsing or refractory multiple myeloma. METHOD: Well-documented patients with relapsing or refractory multiple myeloma, who had received no more than two prior combination chemotherapy regimens, were treated with docetaxel 75 mgm(-2) intravenously over 1h every 3 weeks. Patients were evaluated after two and four cycles of treatment. Standard ECOG criteria were used to evaluate for response and toxicity. RESULTS: The study accrued 31 patients with 28 eligible for response and 30 for toxicity analysis. No objective responses (partial or complete) were found. One patient died due to pneumonia. The majority of patients (80%) developed grade 3-4 granulocytopenia and 23% experienced grade 3-4 thrombocytopenia. The median number of cycles was three. The median survival was 9.9 months. CONCLUSION: Docetaxel was inactive in patients with relapsing or refractory multiple myeloma. In addition, at 75 mgm(-2) every 3 weeks, there was extensive hematological toxicity. It is unlikely that a change in dose or a different schedule would significantly improve response, limit toxicity, and improve survival in patients with multiple myeloma.     

DNA hypermethylation and clinicopathological features in breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study

Aberrant DNA hypermethylation of gene promoter regions has been increasingly recognized as a common molecular alteration in carcinogenesis. We evaluated the association between major clinicopathological features and hypermethylation of genes in tumors among 803 incidence breast cancer cases from a large population-based case–control study conducted in Western New York State. DNA samples were isolated from archive paraffin embedded tumor tissue and were analyzed for hypermethylation status of the E-cadherin, p16, and RAR-β ₂ genes using real time methylation-specific polymerase chain reaction. The frequencies of hypermethylation were 20.0% for E-cadherin, 25.9% for p16, and 27.5% for RAR-β ₂ genes. For postmenopausal women, hypermethylation of E-cadherin tended to be more likely in progesterone receptor (PR) negative than in PR-positive tumors (odds ratio (OR), 1.41; 95% confidence interval (CI), 0.91–2.18). Hypermethylation of p16 tended to be more frequent among estrogen receptor (ER) negative cases than ER-positive cases (OR, 1.51; 95% CI, 1.01–2.32). Hypermethylation of RAR-β ₂ gene was inversely associated with histological and nuclear grade of breast cancer.     

PD-L1表达与胃癌预后及临床病理特征相关性Meta分析

目的 程序性死亡受体-配体1(programmed cell death-Ligand 1,PD-L1)在恶性肿瘤的免疫逃逸中起到重要作用.本研究采用Meta分析评价方法,探讨PD-L1表达与胃癌预后及临床病理特征的相关性.方法 检索Medline/PubMed、EMBASE、Cochrane Library、Springer、万方、维普和中国知网等数据库,收集2016-05-25前公开发表的关于PD-L1表达与胃癌预后相关性的回顾性队列研究.采用RevMan5.3软件进行Meta分析,Newcastle-OttawaScale (NOS)量表进行文献质量评价,漏斗图评估文献的发表偏移.采用比值比(odds ratio,OR)及95％可信区间(confidence interval,CI)评价关联强度.结果 共纳入8篇文献(1 322例患者)进行Meta分析.结果显示,PD-L1阳性表达与胃癌患者3年总体生存率(OR=2.88,95％CI:2.19～3.79,P＜0.001)及5年总体生存率(OR=2.95,95％CI:1.70～5.10,P＜0.001)降低有关.PD-L1表达差异与淋巴结转移(OR=3.32,95％CI:2.35～4.68,P＜0.001)、肿瘤大小(OR=1.52,95％CI:1.12～2.05,P=0.007)有关,而与性别(OR=1.14,95％CI:0.89～1.46,P=0.290)、分化程度(OR=1.02,95％CI:0.68～1.53,P=0.920)、浸润深度(OR=2.14,95％CI:0.93～4.94,P=0.080)、TNM分期(OR=1.99,95％CI:0.77～5.16,P=0.160)无关.结论 PD-L1与胃癌预后有关,其阳性表达在淋巴结转移阳性、肿瘤直径＞5 cm的胃癌患者中更常见.     

Amplifications of TAOS1 and EMS1 genes in oral carcinogenesis: association with clinicopathological features

Amplification of chromosomal region 11q13 is one of the genetic alterations most frequently observed in oral squamous cell carcinoma (OSCC). Both TAOS1, a recently identified gene, and EMS1 were thought as two important target oncogenes for driving 11q13 amplification, and their contributions to oral carcinogenesis were hypothesized. Therefore we investigated amplifications of TAOS1 and EMS1 genes and their relations to clinicopathological variables in premalignant lesions (leukoplakias) and primary OSCC. TAOS1 amplification, beginning from mild-dysplastic epithelia, occurred in 33.3% of leukoplakias and 51.5% of OSCC. EMS1 amplification, beginning from moderate-dysplastic epithelia, occurred in 20% of leukoplakias and 57.6% of OSCC. Both gene amplifications were significantly related to different stages of oral carcinogenesis (p<0.05). During multistage carcinogenesis, no gene amplification was observed in normal tissue and non-dysplastic leukoplakias while, in OSCC with metastasis, amplification frequency increased significantly (p<0.005). Both TAOS1 and EMS1 amplifications were significantly associated with larger tumor size, presence of lymph node metastasis, poor histological differentiation and advanced clinical stage. Our data suggested potential roles in oral carcinogenesis and that TAOS1 might be involved earlier than EMS1. Both genes might be candidate biomarkers for diagnosis and prognosis in OSCC.     

Novel leukemic lymphoma with probable derivation from immature stage of natural killer (NK) lineage in an aged patient

A 66-year-old male patient was admitted with dyspnea; physical examination revealed petechiae and systemic lymphadenopathy. Laboratory findings showed leukemia. The blasts in the peripheral blood were negative for cytochemical myeloperoxidase, and had condensed nuclear chromatin with a nucleolus. The histological diagnosis of the biopsied neck lymph node was lymphoblastic lymphoma. The leukemia cells expressed CD2, CD6, CD7, CD13^low, CD56, β chain of IL-2 receptor^low (IL-2Rβ), and HLA-DR antigens, but not other pan-T (CD5, CD3, CD4, and CD8); pan-B (CD10, CD19, CD20, and CD24); natural killer (NK) (CD16, CD57); or myeloid (CD33) antigens. Electronmicroscopy revealed convoluted nuclei with conspicuous nucleoli and peripherally condensed heterochromatin. Membrane-bound granules containing an electron dense matrix were observed in the cytoplasm, indicating the NK cell nature of the neoplastic cells. While terminal deoxynucleotidyl transferase (TdT) and cytoplasmic CD3 were not detected by immunofluorescence on fixed smears, Northern blot analysis revealed the gene expression of CD3σ, CD3ζ, and TdT. Gene rearrangement analysis revealed that the β, γ, and δ chains of T-cell receptor (TCR) and immunoglobulin heavy chain (IgH) were of germline genotype. While the overall interpretation of the phenotype and genotype was difficult, the derivation of an immature stage of NK lineage was strongly suggested, based predominantly on the electronmicroscopic features. Despite initially successful chemotherapy, the patient died 14 months after initial presentation.     

Expression of BNIP3 in invasive breast cancer: correlations with the hypoxic response and clinicopathological features

Background  

Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) is a pro-apoptotic member of the Bcl-2 family induced under hypoxia. Low or absent expression has recently been described in human tumors, including gastrointestinal tumors, resulting in poor prognosis. Little is known about BNIP3 expression in invasive breast cancer. The aim of the present study was to investigate the expression of BNIP3 in invasive breast cancer at the mRNA and protein level in correlation with the hypoxic response and clinicopathological features.     

Loss of Fhit expression in non-small-cell lung cancer: correlation with molecular genetic abnormalities and clinicopathological features

The FHIT gene is located at a chromosomal site (3p14.2) which is commonly affected by translocations and deletions in human neoplasia. Although FHIT alterations at the DNA and RNA level are frequent in many types of tumours, the biological and clinical significance of these changes is not clear. In this study we aimed at correlating loss of Fhit protein expression with a large number of molecular genetic and clinical parameters in a well-characterized cohort of non-small-cell lung cancers (NSCLCs). Paraffin sections of 99 non-small-cell carcinomas were reacted with an anti-Fhit polyclonal antibody in a standard immunohistochemical reaction. Abnormal cases were characterized by complete loss of cytoplasmic Fhit staining. The Fhit staining results were then correlated with previously obtained clinical and molecular data. Fifty-two of 99 tumours lacked cytoplasmic Fhit staining, with preserved reactivity in adjacent normal cells. Lack of Fhit staining correlated with: loss of heterozygosity (LOH) at the FHIT 3p14.2 locus, but not at other loci on 3p; squamous histology; LOH at 17p13 and 5q but not with LOH at multiple other suspected tumour suppressor gene loci; and was inversely correlated with codon 12 mutations in K-ras. Fhit expression was not correlated overall with a variety of clinical parameters including survival and was not associated with abnormalities of immunohistochemical expression of p53, RB, and p16. All of these findings are consistent with loss of Fhit protein expression being as frequent an abnormality in lung cancer pathogenesis as are p53 and p16 protein abnormalities and that such loss occurs independently of the commitment to the metastatic state and of most other molecular abnormalities.