Telomerase is an RNA-dependent DNA polymerase that synthesizes TTAGGG telomeric DNA onto chromosomal ends to compensate for sequence loss during replication. It has been detected in a variety of human malignancies, suggesting that such activity may play a role in the tumorigenic process. To determine whether telomerase is reactivated in malignant fibrous histiocytoma, 12 tissue samples with this tumor were analyzed for the telomerase activity by a radioactive PCR-based TRAP (telomeric repeat amplification protocol) assay. All of the tumors were further investigated for the expression of human telomerase RNA (hTR) by an in situ hybridization (ISH). Telomerase activity was detected in one (8.3%) sample. Expression of hTR was demonstrated in 7 (58.3%): one telomerase-positive and six telomerase-negatives. These data indicate that the reactivation of telomerase is an uncommon event and not an important factor involved in tumorigenesis in malignant fibrous histiocytoma. It is noteworthy that 50% of the patients with grade 2 tumors expressed hTR, suggesting that telomerase RNA may be useful as a marker for identifying tumor aggressiveness earlier than the conventional histopathologic grading scale.
Carcinogenesis ; DNA ; Histiocytoma, Malignant Fibrous* ; Humans ; In Situ Hybridization ; RNA* ; RNA-Directed DNA Polymerase ; Telomerase*

BACKGROUND: The catalytic subunit of telomerase, hTERT (telomerase reverse transcriptase), is one of the most important components of telomerase, and performs a pivotal role in the mechanism underlying the regulation of telomerase activity in cellular immortalization and carcinogenesis. The principal objective of this study was to investigate hTERT expression in patients with non-small cell lung carcinomas (NSCLCs), and to evaluate its clinical significance and association with the expression of p16 and p53. METHODS: Using tissue microarray, the protein expression profiles of hTERT, p16 and p53 were investigated via immunohistochemistry in 167 samples of NSCLCs. RESULTS: Expression was observed in 54.5% (91/167) of the tumors, which were predominantly squamous cell carcinomas. Patients evidencing hTERT expression in their tumors exhibited significantly poorer survival rates than did patients without hTERT expression in early-stage NSCLCs (p=0.0125). According to the results of our Cox regression analysis, hTERT expression proved to be an independent prognostic factor (p=0.006), particularly for squamous cell carcinomas (p=0.019). hTERT expression was not correlated with p16 expression, but was rather associated with the expression of p53 (p=0.002). CONCLUSIONS: Our results show that hTERT may perform a function in the progression of NSCLC, and that its detection may be useful in predicting the prognosis of NSCLC patients in the early stages of the disease, as well as in the development of a targeted therapy in these tumors.
Carcinogenesis ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Catalytic Domain ; Humans ; Immunohistochemistry ; Lung* ; Prognosis ; Survival Rate ; Telomerase*

Linear nevus sebaceous syndrome is an uncommon neurocutaneous disorder characterized by nevus sebaceus, seizures, and mental retardation, and is often accompanied by ocular anormalies. We recently experienced a case of conjunctival choristoma associated with linear nevus sebaceous syndrome in a 17-month-old boy. The child was the product of a full-term uncomplicated pregnancy and normal delivery with normal karyotype of 46, XY. He was noted at birth to have a conjunctival mass on the right eye and linear nevi over the midline facial region and right temporoparietal scalp. Ophthalmologic examination revealed optic atrophy, peripapillary staphyloma, macular hypogenesis, and osseous choristoma of the choroid. A computed tomography scan demonstrated widening of the subarachnoid space and moderate atrophy of the cerebral and cerebellar hemispheres. He has been followed by ophthalmology and completely free of seizures since birth. The patient underwent excision of the conjunctival mass and biopsies of the skin lesion at 17 months of age. Histologic examination of the skin biopsies was characteristic for the linear sebaceous nevus of Jadassohn. Histologic findings of the conjunctival lesion showed a complex choristoma that contained lacrimal gland tissue and cartilage.
Atrophy ; Biopsy ; Cartilage ; Child ; Choristoma* ; Choroid ; Humans ; Infant ; Intellectual Disability ; Karyotype ; Lacrimal Apparatus ; Male ; Neurocutaneous Syndromes ; Nevus* ; Nevus, Sebaceous of Jadassohn ; Ophthalmology ; Optic Atrophy ; Parturition ; Pregnancy ; Scalp ; Seizures ; Skin ; Subarachnoid Space

BACKGROUND: The claudins are a family of transmembrane proteins associated with tight junctions and they are critical for maintaining cell-to-cell adhesion in sheets of epithelial cells. However, their role in the progression of cancer remains largely unexplored. The aims of this study were to evaluate the expression patterns of claudin-1 and -4 in benign lesions and invasive ductal carcinomas (IDC) of the breast, and relationships between the expression of these markers and the clinicopathological characteristics in IDC patients. METHODS: We examined the claudin-1 and -4 protein expressions by performing immunohistochemical stainings in 54 benign lesions and 120 IDCs via the tissue microarray method. We evaluated the correlation between the expression of these markers and the clinicopathological characteristics of IDC. RESULTS: The expressions of claudin-1 (p=0.099) and -4 (p=0.000) were up-regulated in IDCs as compared with benign lesions. The claudin-1 expression correlated with the loss of estrogen receptor (p=0.036) and progesterone receptor (p=0.011). The claudin-4 expression correlated with lymph node metastasis (p=0.043), the nuclear grade (p=0.030), the histologic grade (p=0.007), and the loss of estrogen receptor (p=0.001) and progesterone receptor (p= 0.029). CONCLUSIONS: These results suggest that claudin-1 and -4 may play a significant role in the carcinogenesis of IDC of the breast and these may represent novel markers for this disease.
Breast* ; Carcinogenesis ; Carcinoma, Ductal* ; Claudin-1* ; Claudin-4 ; Claudins ; Epithelial Cells ; Estrogens ; Humans ; Immunohistochemistry ; Lymph Nodes ; Neoplasm Metastasis ; Receptors, Progesterone ; Tight Junctions

BACKGROUND: The p73 is a recently identified homologue of the tumor suppressor gene, p53, and it has been found to induce apoptosis and inhibit cell proliferation. However, its role in the development of tumors is unclear. This study examined the expression of p73 in patients with non-small cell lung carcinomas (NSCLCs) to determine its clinical significance and association with the expressions of p53, pRb, and mdm2. METHODS: A total of 183 NSCLCs were analyzed immunohistochemically using a tissue microarray. RESULTS: The p73 protein was expressed in the cell nuclei in 156 (85.2%) out of the 183 cases. There was no correlation between the p73 expression and the clinicopathological variables. However, there was a correlation between the p73 expression and the mdm2 and pRb expressions. Multivariate Cox survival analysis identified tumor size and lymph node metastasis to be independent prognostic factors, but the p73 expression was not found to be associated with the patients' survival. CONCLUSIONS: p73 is commonly expressed in NSCLC and it might, in conjunction with pRb and mdm2, be involved in the development of these tumors.
Apoptosis ; Carcinoma, Non-Small-Cell Lung ; Cell Nucleus ; Cell Proliferation ; Genes, Tumor Suppressor ; Humans ; Lung* ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis

PURPOSE: There is evidence supporting the concept of tumor progression from pulmonary adenocarcinoma in situ (formerly bronchioloalveolar carcinoma, BAC) to adenocarcinoma with varying degrees of invasion. The aim of this study was to investigate the role of transforming growth factor beta1 (TGFbeta1) in tumor invasiveness in lung adenocarcinoma, and to determine the potential relationships between its expression and immunophenotypes of cell adhesion molecules. MATERIALS AND METHODS: Tumor samples from adenocarcinoma in situ (n=13), minimally invasive adenocarcinoma (formerly BAC with < or =5 mm invasion, n=2), and lepidic predominant invasive adenocarcinoma (formerly mixed adenocarcinoma showing non-mucinous BAC features with >5 mm invasion, n=25) were examined for the expression of TGFbeta1, E-cadherin, N-cadherin, and H-cadherin proteins using immunohistochemistry. RESULTS: Of a total of 40 cases, 25 (63%) were positive for TGFbeta1. The frequency of immunoreactivity in patients with adenocarcinoma in situ, minimally invasive adenocarcinoma, and lepidic predominant invasive adenocarcinoma was 23% (3/13), 50% (1/2), and 84% (21/25), respectively (p=0.001). TGFbeta1 correlated with T classification (p=0.006) and stage (p=0.001). Loss of E-cadherin expression was more frequently observed in invasive adenocarcinomas than in adenocarcinomas in situ (p=0.034). E-cadherin expression inversely correlated with T classification (p=0.009). TGFbeta1 expression showed a statistically significant correlation with H-cadherin expression (p=0.040), but not with E-cadherin expression (p=0.752). CONCLUSION: These results suggest that TGFbeta1 and E-cadherin may play an important role in invasive progression of lung adenocarcinoma through regulating epithelial-to-mesenchymal transition.
Adenocarcinoma ; Adenocarcinoma, Bronchiolo-Alveolar ; Cadherins ; Cell Adhesion ; Humans ; Lung ; Lung Neoplasms ; Proteins ; Transforming Growth Factor beta1 ; Transforming Growth Factors

PURPOSE: Although both platinum-based drugs and third-generation drugs are commonly used as first-line therapy for patients with advanced, unresectable non-small cell lung cancer, their effectiveness and clinical outcomes vary. We investigated whether epidermal growth factor receptor (EGFR) and HER-2 were correlated with the chemoresponse and survival after treatment with a cisplatin plus paclitaxel regimen. MATERIALS AND METHODS: Forty-nine tumors were analyzed by chromogenic in situ hybridization (CISH) for EGFR and HER-2 gene amplification. RESULTS: Twenty-eight patients (57%) achieved a partial response (PR), 13 (27%) showed stable disease (SD) and 8 (16%) had progressive disease (PD). EGFR and HER-2 amplification was identified in 43% and 57% of the tumors, respectively. EGFR amplification revealed no association with either a chemoresponse or survival, whereas HER-2 was amplified more frequently in the patients with PD (88% vs. 54%, respectively, p=0.06) and in the patients with shorter survival (12 months vs. 20 months respectively, p=0.027). CONCLUSION: The evaluation of HER-2 gene amplification is a promising approach for identifying those patients who are most likely to benefit from combination chemotherapy with cisplatin and paclitaxel
Carcinoma, Non-Small-Cell Lung ; Cisplatin ; Drug Therapy, Combination ; Genes, erbB-2 ; Humans ; In Situ Hybridization ; Paclitaxel ; Receptor, Epidermal Growth Factor

PURPOSE: Telomerase is an RNA-dependent DNA polymerase that synthesizes TTAGGG telomeric DNA onto chromosome ends to compensate for sequence loss during DNA replication. It has been detected in 85~90% of all primary human cancers, implicating that its apparent reactivation in tumors may play a role in the tumorigenic process. The purpose of this study was to evaluate telomerase activity in stomach cancer, and to determine whether methacarn-fixed paraffin-embedded tissues can replace frozen tissue sections for the telomerase (TRAP) assay. MATERIALS AND METHODS: Frozen and corresponding methacarn-fixed paraffin-embedded tissue samples were obtained from 51 patients with gastric adenocarcinoma and analyzed for telomerase activity by using a TRAPeze ELISA kit. RESULTS: Telomerase activity was detected in 37 (73%) frozen samples, and in 13 (25%) methacarn-fixed paraffin blocks. Telomerase activity was well correlated with depth of invasion (p=.037) and tumor differentiation (p=.022). CONCLUSION: These data suggest that reactivated telomerase may play a significant role in the tumorigenesis of gastric cancer and may reflect the malignant potential of the tumor. It is noteworthy that methacarn- fixed tissue cannot as yet substitute for the frozen tissue in the TRAP assay.
Adenocarcinoma* ; Carcinogenesis ; DNA ; DNA Replication ; Enzyme-Linked Immunosorbent Assay ; Humans ; Paraffin ; RNA-Directed DNA Polymerase ; Stomach Neoplasms ; Telomerase*

Benign lymph node inclusions are rare, and can be mistaken for metastasis. We report, herein, a case of a 50-year-old woman who underwent a hysterectomy, with a lymphadenectomy, for an endometrial carcinoma. There was no lymph node metastasis; however, the left external and common iliac lymph nodes demonstrated a few glands, consistent with M llerian-type inclusions (endosalpingiosis). Awareness of these lesions is important to avoid either unnecessary therapy or any delay in treatment. Furthermore, pelvic and aortic lymphadenectomies may be warranted, as neoplastic transformation of preexisting metaplastic tubal-type epithelium is strongly suggested. This paper presents a case of intranodal endosalpingiosis mimicking metastasis.
Endometrial Neoplasms ; Epithelium ; Female ; Humans ; Hysterectomy ; Lymph Node Excision ; Lymph Nodes* ; Middle Aged ; Neoplasm Metastasis*

PURPOSE: Sarcomas have rarely been analyzed for telomerase, which is an RNA-dependent DNA polymerase to maintain telomeres and prevent telomere shortening. This study was undertaken to determine telomerase activity and the expression of the telomerase subunits human telomerase RNA (hTR) and telomerase reverse transcriptase (TERT) in soft tissue sarcomas. MATERIALS AND METHODS: Twenty three sarcomas were analyzed for the telomerase activity by a radioactive PCR-based TRAP assay. All of the samples were further investigated for the expression of hTR by in situ hybridization and for TERT and p53 by immunohistochemistry. RESULTS: Telomerase activity was detected in four (17%) samples. Expression of hTR was demonstrated in 11 (48%) cases, whereas TERT was expressed in 20 (87%).Of the four telomerase-positive tumors, three were positive for both hTR and TERT, and one was positive only for TERT. p53 overexpression was observed in nine (39%) tumors. The frequency of p53 expression increased as the tumor grade advanced (p= .064). CONCLUSION: These data indicate that the reactivation of telomerase is an uncommon event in human soft tissue sarcomas. The high frequency of the expression of hTR and TERT in these tumors suggests that telomerase activity may be regulated at the transcriptional level and an additional event leading to telomerase activation exist.
Humans* ; Immunohistochemistry ; In Situ Hybridization ; RNA ; RNA-Directed DNA Polymerase ; Sarcoma* ; Telomerase* ; Telomere ; Telomere Shortening