Letters to the editor

Gerdes, Johannes; Becker, M. H. G.; Key, Göran; Cattoretti, Giorgio; Sanders, Harry; Smith, A. G.; Darnton, S. Jane; Gray, Michael R.; Crocker, J

doi:10.1002/path.1711680114

Cited by 284 publications

(10 citation statements)

References 13 publications

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“…lc). This is expected because the Ki-67 antigen is present in cells in GI, S, G2, and M (11,16), while the cyclin A protein is present only in the nuclei of cells in S and G2. Anti-cyclin B also predictably stained a subset of Ki-67-positive cells in the cytoplasm (Fig.…”

Section: Resultsmentioning

confidence: 98%

Cyclins as markers of tumor proliferation: immunocytochemical studies in breast cancer.

Dutta

Chandra

Leiter

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

151

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We have developed methods to use anticyclin A, B, and E antibodies as reagents to specifically detect proliferating cells in specific phases of the cell cycle in formalin-fixed, paraffin-embedded sections of tissues and cells. Staining of 48 archival cases of breast cancer showed that these antibodies estimate the tumor proliferation fraction and therefore are potentially useful for the prediction of prognosis. A subset of cancers had a high frequency of tumor cells expressing cyclins A and E, out of proportion to other proliferation markers, suggesting that these tumors may have deregulated cyclin expression. In addition to recognizing authentic cyclin E in the nucleus of proliferating cells, anticyclin E antibody cross-reacted with a cytoplasmic protein in nonproliferating endothelial cells. This cross-reaction allows the simultaneous visualization and quantitation of microvessels in the tumors, measuring a second potential predictor of breast cancer prognosis, tumor angiogenesis.Cyclins are proteins that vary in abundance and associate with and activate different cyclin-dependent kinases (cdk) at different stages of the cell cycle, a given cyclin-cdk complex being essential for passage through a specific stage in the cycle. The periodic appearance of the cyclins in distinct phases of the cell cycle suggests that they can be used as markers for proliferation of tissues. Because the three different cyclins mark different phases of the cell cycle-E for G1 and early S, A for S and G2, and B for late G2 (1-3)-the fraction of cells positive for a given cyclin should predict the fraction in a given phase of the cell cycle. Further, increased expression of various cyclins has been noted in extracts of human cancers, cyclin E in particular being markedly elevated in multiple tumors of different origins (4, 5), and an easy method for detecting such tumors will allow their biological behavior to be separately followed in clinical studies. Estimation of the proliferative behavior of a tumor is important for the management and prognosis of breast cancers. After local excision of node-negative tumors, two-thirds of the patients are expected to do well without further adjuvant therapy, and one-third are expected to relapse. Since chemotherapy is most effective before widespread metastases, it is useful to be able to predict which cancers are likely to recur in order to avoid undertreating these patients or overtreating patients whose tumors are not expected to recur (6, 7). One such prognostic factor is the S phase fraction (SPF) of the tumor estimated by fluorescence-activated cell sorting (FACS) analysis for DNA content of singly suspended tumor cells (8-10). Patients with a large fraction of tumor cells in S and G2 have a poorer prognosis and SPF has been used to guide the selection of patients for adjuvant therapy.Despite its value, flow cytometry of breast cancers is not performed widely, mostly because such analyses require fresh, relatively large tumors with enough tumor left over after tissueThe publication ...

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Section: Resultsmentioning

confidence: 98%

Cyclins as markers of tumor proliferation: immunocytochemical studies in breast cancer.

Dutta

Chandra

Leiter

et al. 1995

Proc. Natl. Acad. Sci. U.S.A.

151

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“…Ki-67 is an accepted means for the detection of proliferating cells in paraffin-embedded tissue sections Gerdes et al, 1992;Mucci et al, 2000), and its expression has been shown to be associated with poor outcome in prostate cancer patients (Borre et al, 1998). Standard avidin -biotin complex immunohistochemistry was used for staining the animal tumours.…”

Section: Immunohistochemistry and Quantitative Assessment Of Ki-67 Prmentioning

confidence: 99%

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

et al. 2004

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Histone deacetylase inhibitors (HDACs) are known to exhibit antiproliferative effects on various carcinoma cells. In this study, the in vivo efficiency of two HDACs, sodium butyrate and tributyrin, on prostate cancer growth inhibition were investigated. To gain an insight into the possible underlying pathways, cell culture experiments were performed focusing on the expression of p21, Rb and cmyc. For in vivo testing, prostate cancer cell lines (PC3 and TSU-Pr1) were seeded on the chorioallantois membrane (CAM) and implanted in a xenograft model using nude mice. Standard Western blot analysis was performed for protein expression of p21, Rb and c-myc in HDAC-treated vs untreated prostate cancer cells. Both sodium butyrate and tributyrin had a considerable treatment effect on microtumours on the chicken egg at already very low concentrations of 0.1 mM. Tributyrin-treated tumours showed the strongest effect with 38% apoptotic nuclei in the prostate cancer cell line PC3. In the mouse model, there was almost no difference between sodium butyrate and tributyrin. In untreated animals the tumours were almost double the size 4 weeks after implantation. Tumours of the treatment groups had a significantly lower percentage of Ki-67-positive-stained nuclei. As demonstrated by Western blot analysis, these effects seem to be independent of p53 status and a pathway via p21 -Rb -c-myc is possibly involved. In this study we have demonstrated a substantial in vivo treatment effect, which can be induced by the application of sodium butyrate or the orally applicable tributyrin in human prostate cancer. The given results may provide the rationale to apply these drugs in well-controlled clinical trials in patients being at high risk of recurrence after specific therapy or in patients with locally or distant advanced prostate cancer.

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“…MIB-1 raised against recombinant parts of the Ki-67 antigen and works in formalin-fixed, paraffin-embedded tissue section. The monoclonal antibody MIB-1 (Immunotech, SA, Marseille, France) sufficiently reliably recognizes the Ki-67 antigen in routinely processed materials [6]. Tissue sections were deparaffinized and dehydrated.…”

Section: Methodsmentioning

confidence: 99%

Mitotic Index Is the Best Predictive Factor for Survival of Patients with Resected Hepatocellular Carcinoma

Ouchi¹,

Sugawara²,

Ono³

et al. 2000

Dig Surg

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Background: In patients with hepatocellular carcinoma (HCC), tumor recurrence is not infrequent after resection. It is presumed that characteristics of the tumor such as cellular malignancy might influence the prognosis of the patients in association with tumor stage and radicality of the procedure. Methods: Univariate and multivariate analyses were used to retrospectively determine the clinicopathologic factors potentially related to survival in 40 patients who underwent hepatectomy for HCC. Results: In univariate analysis, tumor stage I or II, mitotic index of 4 or less/10 random high-power fields, solitary tumor, and curative resection were significantly correlated with better survival. In multivariate analysis, the mitotic index and surgical curability were independently significant variables influencing survival of patients, and the mitotic index was the best predictive factor. A highly significant correlation was found between the mitotic index and Ki-67 labeling index. Compared to tumors with a mitotic index of 4 or less, those with a mitotic index of 5 or more had a higher association with multiple tumors and advanced tumor stage, which preclude curative resection. Conclusion: Analysis of the mitotic index is quite simple, and the mitotic index could be a useful factor for predicting the long-term survival of patients with HCC following hepatic resection.

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Letters to the editor

Cited by 284 publications

References 13 publications

Cyclins as markers of tumor proliferation: immunocytochemical studies in breast cancer.

Cyclins as markers of tumor proliferation: immunocytochemical studies in breast cancer.

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

Mitotic Index Is the Best Predictive Factor for Survival of Patients with Resected Hepatocellular Carcinoma

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