INCENP (inner centromere protein) is overexpressed in high grade non-Hodgkin B-cell lymphomas.

Inner centromere protein (INCENP) is a member of the Chromosomal Passenger Complex (CPC), which is a four member protein complex essential for proper completion of mitosis and cell division (cytokinesis). Inappropriate chromosomal segregation and cytokinesis due to deregulated expression of chromosome passenger proteins may lead to aneuploidy and cancer including lymphomas. According to our knowledge this is the first study investigating immunohistochemical expression of INCENP in lymphoma cases and cancer tissues in general. Our purpose was to characterize the expression of INCENP in cases of non-Hodgkin B-cell lymphomas, to compare the immunoreactivity between low and high grades and to evaluate the correlation between INCENP and MIB-1 labeling indices. We examined INCENP and MIB-1 immunoreactivity in paraffin sections of 55 samples of non-Hodgkin B-cell lymphomas, obtained from 55 patients, 31 men and 24 women. Thirty were of high grade and 25 were of low grade. Our results showed significantly higher nuclear immunohistochemical expression of INCENP in high grade B-cell lymphomas versus low grade ones. Also INCENP expression was significantly correlated with MIB-1 labeling index. Taken together our results point to a possible association between increased INCENP immunostaining and B-cell lymphoma aggressiveness and also stress the need for further investigating the expression of INCENP and other mitotic regulatory proteins in lymphomas and other malignant neoplasms.

Co-expression patterns of tumor-associated antigen genes by non-small cell lung carcinomas: implications for immunotherapy.

BACKGROUND: Polyvalent vaccination represents a recent attempt to improve the effectiveness of lung cancer immunotherapy. This study aimed to investigate whether a gene expression pattern of tumor-associated antigens (TAA) would exist indicating that their use will be most appropriate for the polyvalent vaccination of Caucasian non-small cell lung carcinoma (NSCLC) patients. We examined the concomitant expression of genes belonging to different TAA families for which expression frequencies either have never been detected in NSCLC or vary widely in the literature. RESULTS: 15/23 (65%) and 8/23 (35%) tumor samples were found expressing 6-11 and 2-5 out of the 12 examined TAAs, respectively, at levels >1% of the testis reference sample. The most prevalent TAA patterns observed were those of survivin standard (survivin-std)/survivin-2B expressed by 22/23 (95.5%) tumor samples and of survivin-std/survivin-2B/hTERT expressed by 19/23 (82.5%) tumor samples. The expression levels of the survivin-std gene strongly positively correlated to those of the survivin-2B (p=0.001) and the hTERT genes (p=0.031). The number of concomitantly expressed genes was found to be positively correlated to the age of the patients (p=0.001) and the tumor size (p=0.048). METHODS: Tumor material from 23 patients with NSCLC (12 adenocarcinomas, 8 squamous cell carcinomas, 3 bronchiolo-carcinomas) was examined. mRNA transcripts were detected for 5 genes of the survivin family, 5 MAGE-A genes as well as the genes of human telomerase reverse transcriptase (hTERT) and p53, by the use of quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) or semi-quantitative RT-PCR. CONCLUSION: This study provides evidence that, in Caucasian patients with NSCLC, highly prevalent expression patterns of TAA genes, predominantly of overexpressed TAAs, do exist. This result implies that the combined use of these TAA could help in designing more effective NSCLC immunotherapeutic protocols.

Radiofrequency-assisted partial splenectomy: Histopathological and immunological assessment of the splenic remnant in a porcine model.

BACKGROUND: Radiofrequency (RF) ablation has recently been expanded from palliative treatment into tissue-preserving surgery with controversial results. RF has been accused of septic complications and dysfunction of the target organ due to uncontrolled energy distribution. The aim of this study was to evaluate the short- and long-term implications of RF energy to the remaining splenic tissue after laparoscopic and open RF-assisted partial splenectomy. METHODS: Thirty pigs randomly underwent laparoscopic RF partial splenectomy (n = 10), open RF partial splenectomy (n = 10) using the Radionics Cooltip radiofrequency system (Tyco Hellas), while a third group (n = 10) underwent the conventional procedure. Intraoperative parameters were recorded. Complete blood counts, along with splenic function tests, were estimated preoperatively, immediately postoperatively, and at 1 and 6 months after the procedure. Histology was also evaluated. A separate group of five animals randomly undergo conventional resection (n = 2) and open RF resection (n = 3). These animals were sacrificed 1 month postoperatively and were used for histology only. RESULTS: The blood loss was minimal in both RF groups. No septic complications were observed throughout the follow-up period. Laboratory values at 1 month postoperatively showed decreased splenic function in both RF groups. Histology at 1 month was indicative of a chronic inflammatory reaction to the RF groups whereas, in the control group, prominent hypervascular granulated tissue was observed. Six months postoperatively, the platelet count remained elevated in the RF groups. Histology revealed intense fibrosis at the ablation site, as opposed to friable granulated tissue in the conventional group. CONCLUSIONS: Radiofrequency energy acts as an excellent haemostatic tool. The healing process shifts from the thermal injury to chronic inflammatory reaction and, 6 months later, to intense fibrosis as opposed to the hypervascular granulated tissue presented in the nonablated spleen. However, the longer the RF energy is applied, the more the splenic function is transiently affected.

Indoleamine 2,3-dioxygenase (IDO) expression in lung cancer.

BACKGROUND: The expression of indoleamine 2,3-dioxygenase (IDO) by tumor cells has been considered as a major tumor immune escape mechanism. The aim of this study was to investigate the expression of IDO in lung cancer cell lines as well as in surgically resected lung cancer specimens comparing the latter, to the expression in autologous samples from the corresponding non malignant lung tissue. Correlations of IDO expression with clinicopathological parameters of the disease were performed. METHODS: Nine human lung cancer cell lines and 28 patients with various types of primary lung cancer were enrolled in the study. IDO expression was determined by quantitative real-time PCR using a sample of lung hamartoma as reference. RESULTS: IDO expression was detected in all but three patients' tumor samples, in all but four autologous non malignant lung tissues and in three out of the nine cell lines that were examined. The relative expression of IDO in lung cancer cell lines (4.7 +/- 11.1) was significantly lower than that of all patients' tumor samples (p = 0.006) as well as than that of the autologous non affected lung tissues (p = 0.027). No statistically significant differences were noted between ADC and SCC regarding either the tumor samples or the autologous non affected samples. No significant correlations between IDO expression and clinicopathological parameters were found. CONCLUSION: Direct evidence is provided demonstrating that IDO mRNA can be constitutively expressed by lung cancer cells. The higher IDO expression observed in patients' samples can be attributed to the production of the enzyme by other cells recruited in the tumor microenvironment and the peri-tumoral lung area and/or to its induction by soluble factors of tumor origin.

Comparative evaluation of non-informative HER-2 immunoreactions (2+) in breast carcinomas with FISH, CISH and QRT-PCR.

The routine assessment of HER-2 expression can be affected by many immunohistological preanalytical and analytical variables. The evaluation of non-informative HER-2 tests, because of 2(+) scores, has been addressed in studies using in situ hybridization (fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)). There are very few studies that additionally checked 2(+) cases by quantitative reverse transcription-PCR (QRT-PCR). We analyzed totally 195 breast carcinoma cases, 70 of them showing 2(+) immunoreaction, with FISH/CISH and QRT-PCR. Confirmed amplification in 2(+) cases fell within the reported range (12.8% vs. 8-44%) and some of them showed lower mRNA levels indicating a genuine decrease of HER-2 protein as a mechanism for the non-informative score. In other cases, increased mRNA levels could be ascribed to HER-2 polysomy, verifying previous observations of immunohistologically detectable HER-2 polysomy. A remarkable subset of the 2(+) cases showed "normal" mRNA levels without amplification or polysomy and technical parameters as well as heterogeneity could be incriminated. The overall concordance of QRT-PCR and FISH was 93.8%, highest than most previously reported. Yet, the lack of clear cut-off mRNA values and the challenge of sample microdissection hinder QRT-PCR from claiming the status of a gold standard test for HER-2 evaluation.