Expression of Rsf-1, a chromatin-remodeling gene, in ovarian and breast carcinoma

Rsf-1 protein is a member of a chromatin-remodeling complex that plays an important role in regulating gene expression and cell proliferation. Our previous study showed that Rsf-1 was an amplified gene that participated in the development of ovarian serous carcinoma. To further elucidate the role of Rsf-1 in ovarian cancer, we studied Rsf-1 immunoreactivity in 294 ovarian tumors of various histologic types. Because the Rsf-1 amplicon overlaps an amplified region reported in breast cancer, we included 782 neoplastic and normal breast tissues for comparison. Immunohistochemistry was performed on tissue microarrays using a 4-tiered scoring system. Overexpression of Rsf-1 was defined as a nuclear immunointensity of 3+ to 4+ because of a strong correlation between 3+ and 4+ immunointensity and Rsf-1 gene amplification, based on our previous fluorescence in situ hybridization analysis. Rsf-1 overexpression was observed in 25% of high-grade ovarian serous carcinomas and in only rare cases (<7%) of low-grade ovarian serous, ovarian endometrioid, and invasive breast carcinomas but not in any ovarian serous borderline tumors, ovarian clear cell carcinomas, ovarian mucinous carcinomas, intraductal carcinomas of the breast, and normal ovaries and breast tissues. Thus, overexpression of Rsf-1 was significantly associated with high-grade ovarian serous carcinoma (P < .05), as compared with other types of ovarian tumors and breast carcinomas. Our results provide evidence that Rsf-1 expression is primarily confined to high-grade serous carcinoma, the most aggressive ovarian cancer. Because Rsf-1 overexpression occurs in only a small number of breast carcinomas, it is unlikely that Rsf-1 is a critical gene in the development of breast carcinoma.     

The investigation of foxe1 variations in papillary thyroid carcinoma

Background: Recent reports indicated that incidence of thyroid carcinoma is increasing throughout the worldwide. The aim of our study was to determine a possible relationship between Forkhead box E1 (FOXE1) gene variants and histopathological features of papillary thyroid carcinoma. Methods: FOXE1 gene variations; rs894673, rs1867277 and rs3758249 were analyzed in 57 Papillary thyroid carcinoma patients and 51 age matched healthy control subjects. Restriction fragment length polymorphism (RFLP) technique was used to specifically detect the variations. Results: There was a significant difference in the distribution of rs894673 genotypes in Papillary thyroid carcinoma cases (P=0.01). AA genotype presence of rs1867277 was more significantly associated with several histopathological parameters such as focal and diffuse capsular invasion, lymphatic invasion, P3 with P4 tumor grade and surgical margins. AA genotype presence in rs1867277 variation was significantly associated with the classical variant which is subtype of papillary thyroid carcinoma. Furthermore, the presence of the allel A was found to be related with lymph node invasion risk by 2.46 fold, capsular invasion risk by 2.97 fold, and pT3 with pT4 pathological stage risk by 4.13 fold and the presence of allele A in rs1867277 was significantly associated with classic variants. The presence of allele A in rs1867277 was more significantly associated with several histopathological parameters in classic variant in papillary thyroid carcinoma cases such as, the presence of the A allele was found relationship with lymph node invasion risk by 2.0 fold, capsular invasion risk by 2.39 fold , and pT3 with pT4 pathological stage risk by 3.57 fold. In addition, AATT, AAAA and GATT haplotypes (rs1867277 and rs894673) were evaluated for association with papillary thyroid carcinoma cases. Our results indicate that the significant difference according to two-allele haplotype distribution between papillary thyroid carcinoma cases and control groups. Conclusion: Our findings suggest that FOXE1 variations generate a higher risk for poor histopatological features of papillary thyroid carcinoma.     

Columnar Cell Carcinoma of the Thyroid: MIB-1 Immunoreactivity as a Prognostic Factor

We report a case of columnar cell carcinoma of the thyroid. A 47-year-old Japanese man had a nonencapsulated thyroid mass that infiltrated the surrounding tissues extensively. Seventeen months after thyroidectomy he died of respiratory failure resulting from tracheal invasion. An autopsy showed distant metastases to the liver, lung, esophagus, and pancreas. Histologically, the thyroid mass consisted of tall columnar atypical cells with marked nuclear stratification. About one-fifth of tumor cells were immunopositive for MIB-1. The MIB-1 positive index of our case was extremely high, compared with that of ordinary papillary carcinoma. This case indicates that biological growth activity in columnar cell carcinoma may be similar to that of undiferentiated carcinoma of the thyroid, since the MIB-1-positive index is close to each other.     

Expression of NEDD‐1, a PTEN regulator,in gastric and colorectal carcinomas

Recent studies have disclosed that NEDD4‐1 regulates PTEN activity by ubiquitination. NEDD4‐1 negatively regulates PTEN in cytosol and acts as an oncogenic protein. By contrast, NEDD4‐1 promotes PTEN nuclear import and acts as a tumor suppressor. Despite the importance of NEDD4‐1 in PTEN regulation in cancer cells, expression of NEDD4‐1 protein in cancer tissues is unknown. The aim of this study was to analyze NEDD4‐1 expression in colorectal and gastric cancer tissues. We investigated NEDD4‐1 protein expression in 103 colorectal and 60 gastric carcinoma tissues by immunohistochemistry using a tissue microarray approach. In the cancers, expression of NEDD4‐1 was detected in 82 (80%) of the colorectal carcinomas and 45 (75%) of the gastric carcinomas in cytoplasm. By contrast, the normal mucosal cells of both stomach and colon showed no or very weak expression of NEDD4‐1. There was no significant association of NEDD4‐1 expression with clinicopathologic characteristics, including invasion, metastasis and stage. Our data indicate that NEDD4‐1 overexpression is a feature of both colorectal and gastric carcinomas. The increased expression of NEDD4‐1 in malignant gastric and colorectal cells compared to their normal epithelial cells suggests that NEDD4‐1 expression may play a role in colorectal and gastric cancer development.     

肝癌和大肠癌中染色体1p35─p36的杂合性丢失

通过聚合酶链反应检查肿瘤基因组ＤＮＡ中染色体１ｐ３５－ｐ３６区域Ｄ１Ｓ８０座位的高度多态顺序，在早期肝癌、进展期肝癌和大肠癌中均发现杂合性丢失，检出率分别为２８％（２／７）、３３％（５／１５）和５２％（１２／２３）。结果表明，染色体１ｐ区域存在与肝癌和大肠癌有关的抑癌基因。为抑癌基因的精确定位、克隆或鉴定提供了有价值的参考资料。     

乳腺小管癌与浸润性导管癌中NY-BR-1表达的对比观察

目的 探讨乳腺癌分化抗原NY-BR-1在乳腺小管癌中的表达,并与其在浸润性导管癌中表达进行对比.方法 收集29例小管癌和101例浸润性导管癌石蜡标本,采用免疫组化PV-9000通用型两步法分别进行NY-BR-1、ER、PR、Her-2、Ki-67、nm23、MDR-1及LRP的研究.结果 NY-BR-1在乳腺小管癌和浸润性导管癌中的表达率分别为51.7%、49.5%.NY-BR-1与组织学分化程度密切相关,其在浸润性导管癌组织学Ⅰ～Ⅲ级的阳性率逐渐降低分别为60%、52%、17%.NY-BR-1在小管癌中的表达明显高于浸润性乳腺癌组织学Ⅲ级的表达,差异有统计学意义(P<0.05).NY-BR-1在小管癌和Luminal A型乳腺癌中的表达无差异,在小管癌和浸润性导管癌组织学Ⅰ、Ⅱ级中的表达无差异.NY-BR-1与ER(rs=0.286,P=0.004)、PR(rs=0.252,P=0.010)的表达呈正相关.结论 作为分化抗原的一种,NY-BR-1在低分化的高级别癌中的表达率低,而在高分化的低级别癌中的表达率高.本研究结果显示NY-BR-1在小管癌和低级别浸润性导管癌中的表达率相似,提示小管癌与低级别、luminal型乳腺癌之间具有相似的组织学分化程度.     

Sarcomatoid carcinoma of the pancreas: A case report with immunohistochemical study

Sarcomatoid carcinoma of the pancreas is an uncommon neoplasm. The immunohistochemical characteristics of this unique type of pancreatic tumor were studied. Histologically, there was diffuse proliferation of atypical spindle cells that had hyperchromatic, short, spindle-shaped nuclei and pale cytoplasm. A few tiny foci of small tubular structures were seen in connection with the atypical spindle-shaped cells. Immunohistochemical examination showed that the spindle cells were positive for epithelial cell markers (cytokeratin AE3, cytokeratin AE1, epithelial membrane antigen) and DF3 (MUC1 apomucin-related antigen (ARA)), and were negative for markers such as vimentin, desmin, neuron-specific enolase, and myoglobin. DF3 antigen is known to be expressed in invasive ductal carcinoma of the pancreas and liver, as well as of the breast. Other MUC1-ARA (MY.1E12, MUC1 glycoprotein, HMFG-1, HMFG-2) and anti-CA19-9 were also detected in the present case. Thus, this tumor was diagnosed as anaplastic carcinoma (sarcomatoid carcinoma).     

Syndecan-1 expression in thyroid carcinoma: stromal expression followed by epithelial expression is significantly correlated with dedifferentiation

AIM: To investigate the expression of syndecan-1 in thyroid neoplasia. Syndecan-1 is a proteoglycan regulating cell adhesion. Previous studies have demonstrated that decreased expression of syndecan-1 is linked to malignant progression. METHODS AND RESULTS: Syndecan-1 expression in thyroid neoplasia was studied immunohistochemically. Syndecan-1 was expressed in stromal cells as well as neoplastic epithelial cells. Stromal syndecan-1 expression was observed more frequently in papillary carcinomas larger than 10 mm in size than in microcarcinomas and in widely invasive than in minimally invasive follicular carcinomas. Furthermore, poorly differentiated carcinomas showed this phenomenon more than well-differentiated carcinomas, but the expression in undifferentiated carcinomas was similar to that of poorly differentiated carcinomas. Epithelial syndecan-1 expression was more frequently observed in anaplastic (undifferentiated) carcinomas than in papillary and follicular carcinomas. No significant difference in epithelial expression was found between well and poorly differentiated carcinomas, but undifferentiated carcinomas expressed epithelial syndecan-1 more frequently than did poorly differentiated carcinomas. CONCLUSIONS: These results are in contrast to those previously reported for carcinomas at other sites. It is suggested that the role of syndecan-1 in thyroid carcinomas might be unique. Stromal syndecan-1 expression followed by its epithelial expression is significantly related to progression, including dedifferentiation of thyroid carcinoma.     

Association of Notch1 with vasculogenic mimicry in human hepatocellular carcinoma cell lines

Background and aims: According to recent findings, some tumor cells function as endothelial progenitor cells to initiate tumor vasculogenesis, known as “vasculogenic mimicry” (VM). Notch1, the key regulator of vasculogenesis and embryonic differentiation, has shown a correlation with a poor prognosis in hepatocellular carcinoma (HCC). We attempted to elucidate the relationship between Notch1 and the vascularization of HCC. Materials and methods: HCC cell lines were assayed for tube formation and low-density lipoprotein (LDL) absorption. The translation level of targets of interest was verified using western blot. Notch1 was silenced in HepG2, BEL-7402 and HCCLM6 using lentivirus shRNA. A hypoxic culture was conducted in an anaerobic culture chamber to induce VM in HepG2. Samples from 53 patients with HCC, i.e., 5 with metastasis and 48 without were tested for Notch1⁺ cells and CD34 negative plus Periodic Acid-Schiff (PAS) positive structures, respectively. Results: BEL-7402 and HCCLM6 were capable of tube formation and LDL absorption in vitro, while HepG2 was negative for both. Notch1 down-regulation suppressed endothelial marker expression and greatly impaired tube formation. After hypoxic culture, the tube formation capacity of HepG2 was significantly enhanced, along with an increase in Notch1 expression. Notch1 was strongly and profusely expressed in all 5 cases of distant metastasis, while 19 of the 48 cases without metastasis were sparsely positive (P < 0.05). Notch1 positivity was mainly seen in the cytoplasm and nuclei. VM structures were only found in 2 cases from the metastasis group (P < 0.05). Conclusions: HCC is capable of VM. Notch1 might serve as a potential target for VM development in HCC.     

Excision repair cross-complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin-based chemotherapy

Cisplatin has been the cornerstone of the chemotherapy regimen for urothelial carcinoma. Excision repair cross-complementation group 1 (ERCC1) is a key component of the platinum-DNA repair machinery responsible for nucleotide excision repair. Recent reports have suggested that ERCC1 is a predictive and prognostic marker in solid cancers treated with platinum-based chemotherapy. We performed this study to determine whether or not immunohistochemical expression of ERCC1 can predict objective tumor response and cancer-specific survival in patients with advanced urothelial carcinoma treated with cisplatin-based chemotherapy. We performed a retrospective analysis of 89 patients with advanced or recurrent urothelial cancer, who had undergone treatment at Samsung Medical Center between May 2001 and August 2007. Pretherapeutic biopsy samples from 89 patients with a known tumor response were available. ERCC1 expression was assessed by immunohistochemistry. Of the 89 patients, ERCC1 expression was positive in 49 patients (55%). The overall response rate after chemotherapy was 68.5% (95% CI 54.8-74.8%). Among 61 patients who obtained a response, 27 were negative for ERCC-1 expression and 34 were positive (p = 0.61). Median duration of follow-up was 53.7 months (range 14.4-152.3 months). Progression-free survival (PFS) was 10.6 months for ERCC-1-negative patients and 8.4 months for ERCC-1-positive patients (p = 0.03); the difference in overall survival between patients with ERCC-1-negative tumors and ERCC-1-positive tumors (p = 0.73) was not statistically significant. Other than ERCC1 expression, there was no independent prognostic factor for PFS. These results suggest a negative contribution by ERCC1expression to PFS in metastatic urothelial carcinoma patients treated with cisplatin-based chemotherapy.