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.

Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas.

Caspase-3 is the ultimate executioner caspase that is essential for the nuclear changes associated with apoptosis. We investigated caspase-3 immunohistochemical expression in 58 primary intracranial meningiomas, using one monoclonal antibody detecting both precursor and cleaved caspase-3 (CPP32) and a second recognizing only the cleaved activated form (ASP175). Caspase-3 expression was analyzed in relation to baseline apoptosis-as illustrated by the expression of anti-single stranded DNA (ss-DNA), the antiapoptotic protein bcl-2, proliferation indices (Ki-67, PCNA, topoisomerase IIa, mitosin C), hormonal status (estrogen, progesterone, androgen receptors), standard clinicopathological parameters and patients' disease-free survival. Caspase-3 immunostaining was observed in 62% of cases for CPP32 and in 24% for ASP175. In both instances, the labeling index (LI) was significantly correlated with ss-DNA LI (p=0.038 and p=0.018). CPP32 but not ASP175 LI positively correlated with the mitotic index (p=0.001) and PCNA LI (p=0.004). Both CPP32 and ASP175 LIs were increased in nonbenign meningiomas (p<0.0001 and p=0.0035 respectively). In univariate and multivariate survival analyses, caspase-3 predicted meningioma recurrence, independently affecting disease-free survival (p=0.011 and p=0.047 respectively for CPP32; p<0.0001 and p=0.012 respectively for ASP175). Caspase-3 may prove to be a useful predictor of early recurrence in a group of neoplasms characterized by the frequent discordance between histology and clinical behavior.

Sequential recurrences of ovarian granulosa cell tumour 10 and 11 years after initial diagnosis as haemoperitoneum and subhepatic mass: a case report and review of the literature.

Adult granulosa cell tumours (GCTs) are rare ovarian neoplasms characterised by an indolent course and a propensity for late recurrence. Due to frequent endocrine manifestations most GCTs are diagnosed at an early stage. However, clinical behaviour can not be safely predicted on the basis of conventional clinicopathologic parameters. Surgery remains the cornerstone of therapeutic management. We report on a rare case of a Stage IA GCT twice recurring ten and 11 years after initial surgical treatment. The first recurrence presented as an acute abdomen due to haemoperitoneum after tumour rupture. The second recurrence presented as a subhepatic mass. This case emphasises the need for extended, lifelong follow-up even for patients with early stage, apparently completely removed GCTs. Prognostic parameters and therapeutic options especially for patients with recurrent disease are discussed.

Sarcomas of the head and neck. Results from the treatment of 25 patients.

AIMS: Head and neck sarcomas comprise a heterogenous and biologically diverse group of rare neoplasms. In an effort to clarify some of the obscure clinical behavior of head and neck sarcomas, we present our experience and review the relevant literature. METHODS: Retrospective analysis of patients with histologically proven head and neck sarcomas treated in a tertiary Hospital Department between 1992 and 2002. RESULTS: During this period, 25 patients with head and neck sarcomas were registered. Follow-up ranged from 8 to 144 months. Twenty-three patients were treated with surgery as the primary modality; 14 were treated by surgery alone. Clear margins were obtained in all of them and local control was achieved in 12/13. The 2- and 5-year survival rates for the entire group were 80 and 40%, respectively. Mean overall survival time of our patients was 62 months (median 52 months). CONCLUSIONS: Surgical treatment remains the cornerstone of therapeutic management of head and neck sarcomas.

The favourable prognostic value of oestrogen receptor beta immunohistochemical expression in breast cancer.

AIMS: Oestrogen receptor beta (ERbeta) is present in breast tumours, although its prognostic and pathophysiological roles remain to be established. METHODS: Standard immunohistochemistry with a specific monoclonal antibody was performed on paraffin wax embedded sections; 10% of strongly immunostained carcinoma cells was used as the cutoff point to classify tumours as ERbeta positive. Statistical correlations were sought with clinicopathological variables (including hormone receptor status) and disease free (DFS) and overall survival (OS) in a well documented series of 181 invasive breast carcinomas. Cell proliferation was assessed immunohistochemically by topoisomerase IIa (TopoIIa) index; p53 protein accumulation and c-erbB-2 oncoprotein expression were also taken into account. RESULTS: ERbeta immunoreactivity was detected in most specimens (71.2%); it was positively linked to ERalpha immunoreactivity and increased TopoIIalpha index, and inversely to c-erbB-2 overexpression. There were no correlations with p53 immunostaining or other clinicopathological parameters. A significant favourable impact of ERbeta immunopositivity emerged with regard to DFS and OS in both univariate and multivariate analysis; ERbeta immunopositivity retained its favourable significance with regard to DFS in the subgroups of stage I and II patients when they were examined separately. Progesterone receptor expression also had an independent favourable influence on survival, albeit with less significance. In contrast, survival was not significantly influenced by ERalpha status. CONCLUSIONS: Because of the positive association between ERbeta immunoreactivity and TopoIIalpha expression, the presence of ERbeta in breast cancer cells could be considered an indication of increased proliferation. Nevertheless, ERbeta immunoreactivity emerges as a valuable, independent indicator of favourable prognosis.

Ampullary carcinoid and jejunal stromal tumour associated with von Recklinghausen's disease presenting as gastrointestinal bleeding and jaundice.

We report a very rare case of a 36-year-old woman with von Recklinghausen's disease, synchronous carcinoid of the ampulla of Vater and stromal tumour of the jejunum, who presented with gastrointestinal bleeding and jaundice.

Association of breast cancer with meningioma.

We report a case of meningioma subsequently developed in a patient with bilateral breast carcinoma, which was originally thought to be single brain metastases. A brief review of the literature is presented with emphasis on the unique association between the two neoplasms, which suggests a possible hormonal relationship. The knowledge of this association is important in the differential diagnosis of patients with breast cancer who develop central nervous system manifestations.