How Reliable Is Ki-67 Immunohistochemistry in Grade 2 Breast Carcinomas? A QA Study of the Swiss Working Group of Breast- and Gynecopathologists

Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. Methods Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. Results The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56–0.72). However, we found very high inter-observer variabilities (Kappa 0.04–0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01–0.04) and intra-observer agreement was likewise poor (Kappa 0.00–0.35). Conclusion Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas

Ectopic B-Type cyclin expression induces mitotic cycles in endoreduplicating Arabidopsis trichomes

Cell differentiation is frequently accompanied by a switch from a mitotic division cycle to an endoreduplication cycle. In endoreduplicating cells, DNA synthesis continues in the absence of cell divisions, and it is speculated that endoreduplication represents a shortened mitotic division cycle [1, 2]. In animals, it has been shown that cells switching from mitotic to endoreduplication cycles continue to express factors controlling the G1-S transition, whereas the transcription of mitotic factors controlling the G2-M transition is negatively regulated [3, 4]. It is unknown how the mitotic factors are repressed and what the functional significance of their suppression is. To test the function of two mitotic; cyclins in an endoreduplication cycle, we expressed CYCLIN B1;1 and CYCLIN B1;2 [5, 6] in unicellular Arabidopsis trichomes. During wild- type development, trichomes undergo an average of four endoreduplication cycles, leading to a DNA content of approximately 32C [7, 8]. We find that ectopic expression of CYCLIN B1;2, not CYCLIN B1;1, induces mitotic divisions resulting in multicellular trichomes. The CYCLIN B1,2-triggered cell divisions appeared normal with respect to both nuclear division and cytokinesis. We show that CYCLIN B1;2 is misexpressed in the siamese mutant, which also produces multicellular trichomes [9]. Additional overexpression of CYCLIN B1;2 in a siamese mutant background caused a strongly enhanced phenotype

Prognostic factors in lymph node metastases of prostatic cancer patients: the size of the metastases but not extranodal extension independently predicts survival

AIMS: To analyse tumour characteristics and the prognostic significance of prostatic cancers with extranodal extension of lymph node metastases (ENE) in 102 node-positive, hormone treatment-naive patients undergoing radical prostatectomy and extended lymphadenectomy. METHODS AND RESULTS: The median number of nodes examined per patient was 21 (range 9-68), and the median follow-up time was 92 months (range 12-191). ENE was observed in 71 patients (70%). They had significantly more, larger and less differentiated nodal metastases, paralleled by significantly larger primary tumours at more advanced stages and with higher Gleason scores than patients without ENE. ENE defined a subgroup with significantly decreased biochemical recurrence-free (P = 0.038) and overall survival (P = 0.037). In multivariate analyses the diameter of the largest metastasis and Gleason score of the primary tumour were independent predictors of survival. CONCLUSIONS: ENE in prostatic cancer is an indicator lesion for advanced/aggressive tumours with poor outcome. However, the strong correlation with larger metastases suggests that ENE may result from their size, which was the only independent risk factor in the metastasizing component. Consequently, histopathological reports should specify the true indicator of poor survival in the lymphadenectomy specimens, which is the size of the largest metastasis in each patient

Phenolic composition of European cranberrybush (Viburnum opulus L.) berries and astringency removal of its commercial juice

Phenolic composition of the European cranberrybush (ECB) (Viburnum opulus L.) juice was determined using high-performance liquid chromatography. The juice contained 2037 mg kg(-1) chlorogenic acid, which was 54% of total phenolics, and several other phenolics such as (+)-catechin, (-)-epicatechin, cyanidin-3-glucoside, cyanidin-3-rutinoside and six different glucosides of quercetin. Because of its strong astringent taste, the juices were treated with various doses of two different types of activated carbons (Granucol Bi and Granucol Ge) in order to remove phenolic compounds. Results revealed that both types of activated carbons were equally effective on astringency removal (P < 0.01). A 20-30% reduction in total phenolics was achieved by application of 2.0-3.0 g L-1 activated carbon which also removed unpleasant taste and odour