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

The expression of the B‐cell marker mb‐1 (CD79a) in Hodgkin&apos;s disease

Recent evidence indicates that membrane‐bound immunoglobulin on B lymphocytes is associated with a molecule which comprises the products of the mb‐1 and B29 genes. This molecule is a highly specific marker for B‐cells, presumably because of its central functional role in antigen triggering, and has recently been clustered as CD79a at the 5th Leucocyte Workshop. Recently there has been controversy surrounding reports of B‐cell antigen expression by Reed–Sternberg and related cells, and we have therefore studied 108 cases of Hodgkin&apos;s disease immunohistochemically using a novel antibody which detects mb‐1 protein in paraffin sections. The results were compared with those achieved using antibody L26 to detect CD20. The mb‐1 protein was present in the neoplastic cells in all 14 cases of lymphocyte predominance Hodgkin&apos;s disease studied, and CD20 immunoreactivity was also found in seven of the eight cases of this subtype studied. Of the non‐lymphocyte predominance cases, 20% (19/94) expressed mb‐1 and 30% (20/67) CD20 in the Reed–Sternberg cells, but the cells positive for either of these two markers usually constituted only a very small proportion of the neoplastic population. However, in occasional cases (one of 94 for mb‐1 and five of 67 for CD20), more than 50% of the neoplastic cells expressed one or both B‐cell antigens. These results confirm the B‐cell origin of the neoplastic cells in lymphocyte predominance Hodgkin&apos;s disease, but they also indicate that, contrary to our previous study, mb‐1 expression may occasionally be found in what appears, on histological grounds, to be other types of Hodgkin&apos;s disease. Copyright © 1994, Wiley Blackwell. All rights reserve

Her2 negative luminal breast carcinoma and Ki-67 evaluation

Aim: To determine the degree of inter-observer variability in defining the percentage of Ki-67 immunohistochemical expression in breast carcinoma cases and to investigate the validity of using the cut-point of 14% for the administration of adjuvant treatment in luminal B (Her2 negative) carcinomas. Materials and methods: 99 ER, PR positive, Her2 negative breast carcinomas were consecutively selected from the Pathology files of &quot; IASO&quot; Women&apos;s Hospital. Ki-67 immunostaining was evaluated by four pathologists from four different institutions. Results: Concerning the whole study group, the inter-observer agreement was substantial. Subgroup analysis upon the cases were at least one observer evaluated Ki-67 as being less than 14% showed that the inter-observer agreement was reduced to fair. Further analysis revealed that both below and above the clinicopathological limit of 14%, stands a &quot; grey zone&quot; of about ±7%, in which inter-observer agreement is weak. Conclusion: The administration of cytotoxic therapy in ER, PR positive, Her2 negative breast carcinomas featuring a Ki-67 labeling index of around 14, should be considered with caution. Probably decision-making should also take under consideration the whole morphological and biological profile of each tumor. © 2012 Elsevier Ltd

Laser-induced fluorescence and reflectance spectroscopy for the discrimination of basal cell carcinoma from the surrounding normal skin tissue

The object of this study was to investigate whether laser-induced skin autofluorescence (LIF) and/or light reflectance spectra could provide a useful contrast between basal cell carcinoma (BCC) tissues and the surrounding healthy skin. Unstained human skin samples, excised from humans undergoing biopsy examination, were irradiated with a nitrogen laser (λ = 337 nm) for excitation of autofluorescence and a tungsten halogen lamp for the reflectance measurements. The ex vivo spectroscopic results were correlated with the histopathology images to distinguish the areas of BCC from those of the surrounding health skin. A simple spectral analysis technique was also applied for better skin diagnosis. In conclusion, it seems that LIF and reflectance spectra could be used to differentiate neoplastic from normal skin tissue using an appropriate classification model analysis. Copyright © 2009 S. Karger AG, Basel

Reduced retinoblastoma gene protein to Ki-67 ratio is an adverse prognostic indicator for ovarian adenocarcinoma patients

Objective. Alterations in the retinoblastoma gene (RB-1) are common in human neoplasia. However, the clinical significance of the deregulated expression of RB-1 in ovarian cancer remains undefined. We therefore conducted a retrospective investigation to clarify the relationships of RB-1 gene protein (pRb) to the percentage of cycling cells, clinicopathologic variables, other G1 interacting proteins and prognosis of nonbenign epithelial ovarian tumors. Methods. Paraffin-embedded tissue from 127 nonbenign epithelial ovarian tumors, including 44 of low malignant potential (LMP) and 83 primary ovarian adenocarcinomas, was stained immunohistochemically for pRb, p21(Cip1), p27(Kip1), p53, and Ki-67 antigen (a cell proliferation associated marker). Expression of these markers was correlated with clinicopathologic features and with overall survival of patients with adenocarcinomas. Results. pRb levels were significantly lower in LMP tumors than in carcinomas (P=0.027). In the latter group, pRb expression decreased with increasing grade (I-II vs III) (P=0.010), advancing stage (I-II vs III) (P&lt;0.001), and bulk residual disease (P=0.014). pRb was not related to Ki-67 expression (P&gt;0.10) or to overall survival (P&gt;0.10) but a low pRb to Ki-67 ratio emerged as an important indicator of poor survival in univariate analysis in the entire cohort (P=0.0076) and in the platinum-treated patients (P=0.0162) as well as in multivariate analysis, along with histologic type and FIGO stage. Conclusions. Diminished pRb levels are related to several clinicopathologic indicators of aggressiveness in ovarian adenocarcinomas. More importantly, pRb expression coupled with the percentage of Ki-67 positive cells is a better prognostic marker than pRb, M-67, or other G1 interacting proteins and supplements the information gained from traditional prognosticators. (C) 2003 Elsevier Science (USA). All rights reserved

Prognostic relevance of apoptotic cell death in non-Hodgkin&apos;s lymphomas: A multivariate survival analysis including Ki67 and p53 oncoprotein expression

Aims: To evaluate the independent prognostic value of apoptotic versus proliferative fractions in a series of 92 patients with non-Hodgkin’s lymphomas (NHL). Methods and results: Apoptotic fractions were quantified by use of the TdT (terminal deoxynucleotidyl-transferase)mediated in-situ end-labelling technique (TUNEL), the percentage of positive cells constituting the apoptotic index (AI). Proliferative rate was expressed as percentage of Ki67 positive cells (Ki67 LI), Tissues were also stained for p53 protein with the DO-1 antibody. Patients were followed up until death (n =33) or for an average of 63 months (n = 56). AI increased with malignancy grade and proliferative activity but was not related to location, cell of origin, clinical stage, bone marrow involvement and p53 expression. In multivariate analysis, overall survival was independently influenced by grade, stage, p53 LI and chemotherapy. The independent predictors of disease-free survival were Ki67 LI location and chemotherapy. AI turned out to be the only independent (negative) predictor of post-relapse survival. On the other hand, a low Ki67 LI increased the risk of relapse (logistic regression analysis) whereas a low p53 LI increased the probability of complete response, Conclusions: Our results suggest that the combined assessment of apoptotic fraction, proliferative rate and p53 expression may provide important prognostic information independent of other clinicopathological parameters in NHL