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, p27Kip1, p21WAF1 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 p27Kip−1 LI (P=0.0068). Finally, both MCM-2 and MCM-5 were associated significantly with adverse patients' outcome in both univariate (⩾20 vs >20%, P=0.0011 and ⩾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

Fetal akinesia deformation sequence in a highly developed acardius twin

We report a case of a holoacardius twin with extremely advanced development of the head, face, upper and lower limbs in the absence of all thoracic and upper abdominal viscera and associated with intestinal and anal atresia. The malformed fetus also had craniofacial abnormalities, hydrops, cystic hygroma of the neck, arthrogryposis and pterygia. The monozygous co-twin was found to be normal. The association of acardia with the typical characteristics of the fetal akinesia deformation sequence has not been previously described in the literature

DNA topoisomerase II alpha expression correlates with cell proliferation but not with recurrence in intracranial meningiomas

Aims: To assess the value of topoisomerase Hot (TopoII alpha) as a novel proliferation-associated molecule, by correlating its immunohistochemical expression with Ki67 MIB-1), cell proliferating cell nuclear antigen (PCNA) and mitotic index in meningiomas. Furthermore. to investigate its relation to standard clinicopathological parameters and patients’ outcome. Methods and results: This retrospective study comprised a consecutive series of 57 patients with primary intracranial benign and atypical meningiomas. Six tumours recurred (10.5%) following complete surgical resection, within a follow-up period ranging from 21 to 108 months (median 60 months). Archival formalin-fixed paraffin-embedded sections were stained with standard immunohistochemical methods. The lower proliferation indices were obtained with TopoII alpha( and the higher ones with PCNA. TopoII alpha labelling index (LI) ranged from 0.1% to 10%, (median 0.5%) and, along with K167 and PCNA LI, increased with malignancy grade (P = 0.049, P = 0.045 and P &lt; 0.001. respectively), displaying though a significant overlapping between grades. A significant positive correlation was shown between TopoII&lt;alpha&gt; and Ki67 (P &lt; 0.001) or PCNA (P = 0.032). In univariate and multivariate survival analysis, TopoII&lt;alpha&gt; failed to predict meningioma recurrence and did not affect disease-free survival. Only tumour size and Ki67 LI provided significant prognostic information in this regard. Conclusions: TopoII alpha expression may be useful as a novel proliferation marker in meningiomas, presenting several advantages over the markers currently in use, notably providing a better estimate of the number of cycling cells and a more uniform nuclear staining pattern. However. it fails to discriminate between benign and atypical neoplasms and does not provide prognostic information beyond that obtained by Ki67

A morphometric study of neovascularization in colorectal carcinoma

BACKGROUND. Neovascularization reportedly is correlated with metastasis, recurrence, and prognosis in some types of tumors. Microvessel quantification in so-called “hot spots” has been studied extensively as the only factor reflecting angiogenesis in Various malignant tumors. The objective of this report was to evaluate multiple morphometric microvascular characteristics in addition to microvessel density (MVD) in colorectal carcinomas to provide a better approach to examining the relation between angiogenesis and clinicopathologic factors and prognosis. METHODS. Histologic sections from 106 colorectal adenocarcinomas and 17 adenomas, immunostained for factor VIII, were evaluated by image analysis for the quantification of MVD, total vascular area (TVA), and microvascular branching, as well as several morphometric parameters related to the vessel size or shape. RESULTS. MVD gradually decreased with progressing Dukes stage. The vascular branching counts were significantly higher in carcinomas than in adenomas, and remained unaffected through progressing Dukes stages. Shape-related parameters showed significant differences between carcinomas and adenomas and between different grades of differentiation. Branching counts and TVA were the only factors found to be of prognostic significance. CONCLUSIONS, This study provides evidence that neovascularization is an early critical event in colorectal tumorigenesis, reaching a maximum level early in the malignant process. Its prognostic significance is better assessed by quantification of TVA and the branching pattern of microvessels, whereas MVD does not provide significant prognostic information for colorectal carcinoma patients. Cancer 1998; 83:2067-75. (C) 1998 American Cancer Society