Prevalence of TERT Promoter Mutations in Orbital Solitary Fibrous Tumors.

The orbital manifestation of a solitary fibrous tumor (SFT) is exceptionally rare and poses specific challenges in diagnosis and treatment. Its rather exceptional behavior among all SFTs comprises a high tendency towards local recurrence, but it rarely culminates in metastatic disease. This raises the question of prognostic factors in orbital SFTs (oSFTs). Telomerase reverse transcriptase (TERT)-promoter mutations have previously been linked to an unfavorable prognosis in SFTs of other locations. We analyzed the prevalence of TERT promoter mutations of SFTs in the orbital compartment. We performed a retrospective, descriptive clinico-histopathological analysis of nine cases of oSFTs between the years of 2017 and 2021. A TERT promoter mutation was present in one case, which was classified with intermediate metastatic risk. Local recurrence or progress occurred in six cases after primary resection; no distant metastases were reported. Multimodal imaging repeatedly showed particular morphologic patterns, including tubular vascular structures and ADC reduction. The prevalence of the TERT promoter mutation in oSFT was 11%, which is similar to the prevalence of extra-meningeal SFTs of the head and neck and lower than that in other extra-meningeal compartments. In the present study, the TERT promoter mutation in oSFT manifested in a case with an unfavorable prognosis, comprising aggressive local tumor growth, local recurrence, and eye loss.

Adjuvant low single dose cisplatin-based concurrent radiochemotherapy of oral cavity and oropharynx carcinoma: impact of extracapsular nodal spread on distant metastases.

BACKGROUND: The aim of this study was to analyze the prognostic importance of extracapsular nodal spread (ECS) in patients with locally advanced squamous cell carcinoma (SCC) of the oral cavity or oropharynx, and the impact of adjuvant low single dose cisplatin-based radiochemotherapy on distant metastases-free survival (DMFS). PATIENTS AND METHODS: The study population was selected from 195 patients with high-risk oral cavity or oropharyngeal cancer, who had either adjuvant radiotherapy (RT) or radiochemotherapy (RCT) between January 1, 1997 and December 31, 2006, at the University Clinic of Radiation Oncology of the Martin-Luther-University Halle-Wittenberg. A total of 42 matched pairs of patients with UICC stage III-IVa,b disease were analyzed. The patients were matched (one to one) according to tumor site, sex, T stage, N stage, ECS, resection margin status, and Karnofsky performance status. To analyze the correlation between the treatment modality (RT vs. RCT) and the impact of ECS on DMFS, the Cox proportional hazard model was used. Survival rates were calculated using the Kaplan-Meier method. RESULTS: There was a strong correlation between the degree of nodal involvement and ECS (pN1: 33%; pN2b: 45%; pN2c: 71%). Moreover, the 5-year locoregional control rates (LC) in patients with ECS were 76% vs. 63% (n.s.) for RT and RCT, respectively. However, for patients without ECS, the LC was more favorable after RCT (RT vs. RCT: 62% vs. 88%, p < 0.05). DMFS again was better after RT, and this observation was independent of the presence or absence of ECS. Finally, in multivariate analyses, the presence of ECS significantly decreased the DMFS (p = 0.04, hazard ratio (HR) 2.64). CONCLUSIONS: Patients with ECS have an increased risk of distant metastases. Adjuvant low single dose cisplatin-based concurrent chemotherapy seems to have no influence on occult microscopic systemic disease.

Small polydispersed circular DNA contains strains of mobile genetic elements and occurs more frequently in permanent cell lines of malignant tumors than in normal lymphocytes.

Small polydispersed circular DNA (spcDNA) belongs to the extrachromosomal pool of DNA and is composed of heterogeneous DNA circles. Whether spcDNA has a special function is currently unclear but their occurrence was suggested to be linked to genetic instability. In this study we investigated as to whether human lymphocytes from healthy volunteers also harbour spcDNA and whether spcDNA is present in all permanent cell lines from human normal and malignant tissues. Moreover, we were interested to see whether spcDNA contains sequences of mobile genetic elements. Our results show that spcDNA is present in all samples investigated yet the amount is lower in normal lymphocytes when compared to cancer cell lines (5.4 vs. 17.8%). Alu sequences were present in 12/16 cancer cell lines whereas LINE-1 (L1) sequences were present in 15 of them. Six tumor cell lines also contained telomeric sequences. In contrast to that, spcDNA of normal lymphocytes contains Alu and L1 sequences only in 3/16 cases and no telomeric sequences at all. Our findings suggest a direct dependency of the amount of Alu and L1 sequences on that of spcDNA. Beside these repetitive sequences, sequencing of spcDNA revealed in most cases chromosomal sequences of almost all chromosomes without an increased frequency of single regions. We suggest that the whole spcDNA including retrotranspositional elements and telomeric sequences may play a role for chromosomal rearrangements and genomic instability.

Glucose transporter GLUT1 in colorectal adenocarcinoma cell lines is inversely correlated with tumour cell proliferation.

The high glucose consumption of tumour cells has been well known since Warburg's investigations. Nevertheless, the reason for this phenomenon is still a matter of speculation. Glucose uptake of tumour cells is mainly mediated by GLUT1. In this study, the question of whether glucose uptake as well as expression of GLUT1 are both related to tumour cell proliferation was addressed. Three kinetically different cell lines of colorectal adenocarcinomas (HRT-18, HT29 and CX-2) were used for the experiments. All the cell lines expressed GLUT1 at a high level, being mainly localized within the cell membrane and the endoplasmic reticulum. Surprisingly, the highest expression of GLUT1 was found in the most slowly proliferating cell line, CX-2. Moreover, induction of cell cycle arrest increased both GLUT1 expression and glucose consumption, as well as global protein synthesis. These data suggest that the protein synthesis of tumour cells is much more glucose-consuming than proliferation and that both processes are inversely related.

Ezrin expression is related to poor prognosis in FIGO stage I endometrioid carcinomas.

As a cortical cytoskeletal protein, ezrin adapts the cytoplasmic tail of CD44 to the actin-based cytoskeleton and is functionally involved in migration and adhesion that are prerequisites for metastasis. To assess the importance of ezrin and its associated protein osteopontin for the progression of endometrioid carcinoma in FIGO stage I, we analyzed paraffin-embedded tissue from 164 patients by immunohistochemistry and correlated these data with clinicopathological parameters. Ezrin was expressed in normal proliferating endometrial glands, as was confirmed by quantitative PCR and immunohistochemistry. In endometrioid carcinoma, enhanced ezrin expression correlated with a reduced overall survival in univariate analysis (P = 0.041). In contrast, no significant correlation was found for osteopontin. In multivariate survival analysis, among FIGO grade 3 and age, ezrin was still found to be an independent risk factor (relative risk 2.2, confidence interval 1.0-5.4, P = 0.047). Hence, elevated ezrin expression is a new independent prognostic marker in FIGO stage I endometrioid carcinoma, and thus provides further evidence for an important role of ezrin in tumor progression.

Ezrin promotes ovarian carcinoma cell invasion and its retained expression predicts poor prognosis in ovarian carcinoma.

The majority of patients diagnosed with ovarian carcinoma are classified as being in advanced stage of disease. In a situation of cancer spread throughout the abdominal cavity, a successful curative treatment is difficult to achieve. Therefore, preventing binding of tumor cells to the mesothelium is crucial for patients' outcome. One important mechanism is the interaction between hyaluronic acid and the CD44 receptor with its submembrane linking complex. This consists of ezrin, radixin, and moesin and connects the CD44 receptor with the cytoskeleton. To assess the role of ezrin and moesinfor ovarian carcinoma progression, we analyzed ovarian carcinoma samples from 105 patients for expression of ezrin and moesin by immunohistochemistry and correlated these data with several clinicopathological parameters. To elucidate the functional importance of ezrin and moesin, their expression was inhibited in SKOV-3 cells by RNA interference. Ezrin and moesin were strongly expressed in 49 and 48% of ovarian carcinoma samples, respectively, and their presence correlated with reduced overall survival in univariate analysis (ezrin, p=0.0189; moesin, p=0.0351). In multivariate analysis (including FIGO stage, residual tumor, histological type, and Silverberg grading), ezrin still remained significant as an independent risk factor (relative risk, 2.39; p=0.012). In SKOV-3 cells, siRNA against ezrin but not moesin inhibited in vitro invasion. These data imply that ezrin is necessary for tumor cell invasion, and the better prognosis of ovarian carcinomas lacking ezrin is probably related to their impaired invasion.