The incidence of HPV infection in anal cancer patients in Greece.

BACKGROUND AND AIM OF THE STUDY: Although anal cancer represents a relatively uncommon malignancy, its incidence over the last five decades, has been reported as increased for both sexes, worldwide. Human papillomavirus (HPV) infection has been shown to be a major cause for its development. The aim of the present study is to report on clinical, epidemiological and virological data of squamous anal cancer in Greek patients. PATIENTS AND METHOD: Between January 2002 and December 2010, 11 Greek patients (6 females) who were diagnosed as suffering from squamous cell anal or perianal cancer, were treated in our Hospital. Formalin fixed paraffin embedded tissue samples, obtained at the time of the anal biopsy or surgery, were analyzed by PCR in order to identify the presence as well as the type of HPV infection. RESULTS: Overall, the presence of HPV DNA was detected in 6 out of the 11 patients (54.5%). The "high risk" HPV DNA was detected in 3 of them (2 women and 1 man), while the "low risk" HPV DNA was detected in the remaining three (2 women and 1 man). CONCLUSION: The incidence of HPV infection in squamous cell anal cancer Greek patients, is lower than other Western countries, probably reflecting differences in sexual habits in the Greek population.

Sox11 expression in astrocytic gliomas: correlation with nestin/c-Met/IDH1-R132H expression phenotypes, p-Stat-3 and survival.

BACKGROUND: Sox11 is a transcription factor expressed in foetal and neoplastic brain tissue, including gliomas. It has been shown to suppress the tumourigenicity of glioma stem cells in vivo, thereby being hypothesised to function as a tumour suppressor. METHODS: We investigated the expression of Sox11 in 132 diffuse astrocytomas in relation to the regulator cell marker nestin, c-Met and IDH1-R132H, which have shown to be differentially expressed among the molecular subgroups of malignant gliomas, as well as to an inducer of astrocytic differentiation, that is, signal transducer and activator of transcription (p-STAT-3), clinicopathological features and survival. RESULTS: Sox11 immunoreactivity was identified in all tumours irrespective of grade, but being correlated with p-STAT-3. Three out of seven cases showed partial Sox11 promoter methylation. In >50% of our cases neoplastic cells coexpressed Sox11 and nestin, a finding further confirmed in primary glioblastoma cell cultures. Furthermore, nestin, c-Met and IDH1-R132H expression differed among grade categories. Cluster analysis identified four groups of patients according to c-Met, nestin and IDH1-R132H expression. The c-Met/nestin high-expressor group displayed a higher Sox11 expression. Sox11 expression was an indicator of favourable prognosis in glioblastomas, which remained in multivariate analysis and validated in an independent set of 72 cases. The c-Met/nestin high-expressor group was marginally with shorter survival in univariate analysis. CONCLUSIONS: We highlight the importance of Sox11 expression as a favourable prognosticator in glioblastomas. c-Met/nestin/IDH1-R132H expression phenotypes recapitulate the molecular subgroups of malignant glioma.

pERK activation in esophageal carcinomas: clinicopathological associations.

MAPK (mitogen-activated protein kinase) pathway is considered a control regulator in various malignant tumors but its role in esophageal carcinomas remains elusive. In our study, we examined the possible prognostic significance of MAPK pathway in human esophageal cancer. We searched for mutations in exons 18-21 of EGFR gene, codons 12 and 13 of K-RAS gene and exon 15 of B-RAF gene by high resolution melting analysis (HRMA) and pyrosequencing in 44 esophageal carcinomas. Immunohistochemistry was performed in 29 cases in order to evaluate expression levels of pERK (extracellular-signal regulated kinase). In one laser microdissected squamous cell carcinoma, a somatic K-RAS mutation at codon 12 was detected, whereas none of the cases displayed mutations in EGFR and B-RAF genes. Elevated nuclear as well as cytoplasmic pERK expression (100% and 62% of cases respectively) was observed independently of EGFR and B-RAF mutational status. Increasing pERK nuclear and cytoplasmic expression as well as the intensity of nuclear staining was found to be significantly correlated with tumor grade in univariate and multivariate statistical analysis. Our findings depict the presence of activated ERK despite the low frequency of upstream alterations, implicating ERK activation in the acquisition of a more aggressive phenotype in esophageal cancer.

Dermatofibrosarcoma: a rare form of soft tissue. Management and review of the literature.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor of cutaneous origin of intermediate grade malignant potential. The incidence of DFSP is 0.1% of all cancers and 1% of all soft tissue sarcomas. We present the case of a 65years old female with a palpable, painful mass on the right thigh. A surgical excision of the lesion was done and the histopathology, as well as the immunohistochemical analysis with CD-34, confirmed the diagnosis of DFSP. Two years later, the patient is free of disease and no local recurrences or metastases have been found. Wide radical excision is the preferred surgical method for therapy of DFSP without distant metastasis. Furthermore, DFSP resists to conventional chemotherapy and radiation therapy, while, in cases of metastasis, therapy depends on cytogenesis and molecular biology of the tumor, so new therapeutic strategies are under research.

Analysis of PIK3CA and B-RAF gene mutations in human astrocytomas: association with activation of ERK and AKT.

OBJECTIVE: The analysis of the presence of PIK3CA and B-RAF gene mutations in relation to ERK and AKT activation in diffusely infiltrating astrocytomas, in order to determine their potential role in tumor aggressiveness. METHODS: Polymerase chain reaction-single strand confirmation polymorphism (PCR-SSCP) and sequencing analysis were used for PIK3CA and B-RAF gene mutation detection. pERK and pAKT expression were examined by immunohistochemistry. RESULTS: PIK3CA mutations were found in 2 (3%) cases of glioblastomas whereas none of these cases displayed mutations in exon 15 of B-RAF gene. Neither low grade astrocytomas nor anaplastic astrocytomas revealed any mutations in these genes. Nuclear and cytoplasmic pERK immunoreactivity was displayed in 100% and 82% of cases, respectively. pERK nuclear expression was positively correlated with pERK cytoplasmic expression (p = 0.0067). Moreover, pERK nuclear expression increased in parallel with tumor grade (II, III v/s IV, p = 0.0262). Nuclear and cytoplasmic pAKT immunoreactivity was displayed in 97% and 100% of cases, respectively. Similarly, pAKT nuclear expression was positively correlated with pAKT cytoplasmic expression (p = 0.0074). pAKT cytoplasmic expression increased with increasing tumor grade (II,III v/s IV, p = 0.0930), although the latter relationship was of marginal significance. pAKT cytoplasmic expression was also positively correlated with pERK nuclear expression (p = 0.0156). CONCLUSIONS: Our study reports the low frequency of PIK3CA and B-RAF mutations in astrocytomas, despite the presence of activated ERK and AKT proteins. Moreover, the correlation of pERK nuclear and pAKT cytoplasmic expression with tumor grade suggests the possible crucial role of the activation of these proteins in human gliomagenesis.

Primary effusion lymphoma in two HIV-negative patients successfully treated with pleurodesis as first-line therapy.

Primary effusion lymphoma (PEL) is a rare non-Hodgkin's lymphoma (NHL) mostly occurring in HIV-positive patients. It is characterized by the development of effusion in one or more body cavities, with no tumor masses and a positive human herpes virus-8 (HHV8) status. It has a poor survival profile and no optimal treatment is yet defined. We report two HIV-negative, HHV8-positive patients with PEL of the pleural cavity who achieved a durable remission after pleurodesis with bleomycin and no systemic therapy. We also perform a review of the relevant literature regarding the clinical data, treatment, and survival of PEL in HIV-negative patients.

Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications.

Minichromosome maintenance proteins (MCM) have recently emerged as novel proliferation markers with prognostic implications in several tumour types. This is the first study investigating MCM-2 and MCM-5 immunohistochemical expression in a series of ovarian adenocarcinomas and low malignant potential (LMP) tumours aiming to determine possible associations with clinicopathological parameters, the conventional proliferation index Ki-67, cell cycle regulators (p53, p27(Kip1), p21(WAF1) and pRb) and patients' outcome. Immunohistochemistry was applied in a series of 43 cases of ovarian LMP tumours and 85 cases of adenocarcinomas. Survival analysis was restricted to adenocarcinomas. The median MCM-2 and MCM-5 labelling indices (LIs) were significantly higher in adenocarcinomas compared to LMP tumours (P<0.0001 for both associations). In adenocarcinomas, the levels of MCM-2 and MCM-5 increased significantly with advancing tumour stage (P=0.0052 and P=0.0180, respectively), whereas both MCM-2 and MCM-5 increased significantly with increasing tumour grade (P=0.0002 and P=0.0006, respectively) and the presence of bulky residual disease (P<0.0001 in both relationships). A strong positive correlation was established between MCM-2 or MCM-5 expression level and Ki-67 LI (P<0.0001) as well as p53 protein (P=0.0038 and P=0.0500, respectively). Moreover, MCM-2 LI was inversely correlated with p27(Kip-1) LI (P=0.0068). Finally, both MCM-2 and MCM-5 were associated significantly with adverse patients' outcome in both univariate (> or =20 vs >20%, P=0.0011 and > or =25 vs <25%, P=0.0100, respectively) and multivariate (P=0.0001 and 0.0090, respectively) analysis. An adequately powered independent group of 45 patients was used in order to validate our results in univariate survival analysis. In this group, MCM-2 and MCM-5 expression retained their prognostic significance (P<0.0001 in both relationships). In conclusion, MCM-2 and MCM-5 proteins appear to be promising as prognostic markers in patients with ovarian adenocarcinomas.

c-FLIP expression in colorectal carcinomas: association with Fas/FasL expression and prognostic implications.

AIMS: Disruption of apoptotic cell death has been implicated in tumour aggressiveness in colonic carcinogenesis. The Fas-Fas ligand (FasL) system is involved in the execution of apoptosis induced by the immune system. c-FLIP protein constitutes an inhibitor of Fas and other (TRAIL) death receptor-mediated apoptosis. The aim of this study was to investigate the simultaneous expression of Fas, FasL and c-FLIP in relation to standard clinicopathological parameters and patients' outcome in colorectal cancer. METHODS AND RESULTS: Levels of Fas, FasL and c-FLIP protein expression were quantified immunohistochemically in paraffin-embedded tissues from 90 patients. Immunopositivity was detected for Fas, FasL and c-FLIP in 71%, 35.5% and 68.8% of cases, respectively. Concurrent expression of Fas/FasL was seen in 28 samples (31%), of which 24 (85.7%) also displayed c-FLIP positivity (P = 0.04). c-FLIP overexpression (> 10%) tended to prevail marginally in higher stage tumours (P = 0.09). Additionally, FasL and c-FLIP adversely affected survival on both univariate (P = 0.001 and P = 0.0024, respectively) and multivariate analysis [hazard ratio (HR) 3.491, P = 0.005 and HR 2.960, P = 0.036, respectively]. CONCLUSIONS: The frequent expression and coexpression of Fas, FasL and c-FLIP in colorectal carcinoma implicates c-FLIP as an inhibitor of the Fas-FasL-induced death pathway in these tumours. Moreover, c-FLIP conveys independent prognostic information in the presence of classical prognosticators.

Leptomeningeal melanoma of unknown primary site: two cases with an atypical presentation of acute meningitis.

Primary melanoma of the central nervous system accounts for only 1% of the cases of melanoma, having a relatively rare frequency of being reported in the literature. We report two cases of leptomeningeal melanoma of unknown primary site diagnosed after post mortem examination. In the first case, the patient presented with resisting epilepsy, whereas in the second with persisting fever and mental slowness. Cranial CT in the first patient showed postgadolinium enhancement of the ependyma and the infundibulum, while in the second there was diffuse enhancement of the leptomeninges. Analyses of the CSF in both cases did not establish the presence of malignant cells but revealed altered CSF glucose and increased CSF protein levels. There were no extracranial abnormalities. Both patients were treated for infectious meningitis and died a few days afterwards. At autopsy, all body cavities including oral cavity and the entire integument were examined. In both cases the leptomeninges were diffusely covered with brownish material. Histological examination of the brain specimens revealed the presence of a malignant neoplasm of low differentiation. Diagnosis was established with the results of immunohistochemistry, tumor cells were positive for HMB-45 and S-100 whereas they were negative for cytokeratins, CD45 and GFAP. In conclusion, both patients, although presenting with symptoms and signs highly suggestive of meningitis, suffered from leptomeningeal melanomas of unknown primary site. Clinical, radiological and histological findings are discussed with a review of the literature.