The relationship between cyclin B1 overexpression and lymph node metastasis in human colorectal cancer

Korenaga, Daisuke; Takesue, Fumio; Yasuda, Mitsuhiro; Honda, Masaaki; Nozoe, Tetsuo; Inutsuka, Sadaaki

doi:10.1067/msy.2002.119362

Cited by 33 publications

(36 citation statements)

References 20 publications

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“…These results are in concordance with previous reports, which demonstrated that cyclin B1 expression is reduced in the invasive margin tissues of colorectal carcinoma, thus indicating reduced cellular proliferation. 6,29 Regarding the prognosis of RCC patients, we again found no association with expression of cyclin B1 in the invasion front tissue specimens.…”

Section: Discussionmentioning

confidence: 62%

“…Therefore, organ specificity or heterogeneity of the expression of cyclin B1 may specifically affect tumor progression and clinical prognosis. 29 We found that positivity of cyclin B1 in primary tumor specimens showed only a tendency towards an impaired survival without reaching statistical significance.…”

Section: Discussionmentioning

confidence: 87%

“…[18][19][20] So far, increased levels of cyclin B1 protein were observed in colon, 21 breast, 22 prostate, 23 oral cavity 24 and gastric cancer. 25 Furthermore, for squamous cell carcinomas of the lung 26 as well as esophageal, 27 tongue 28 and small cell lung cancer, 29 expression of cyclin B1 correlated with increased biological aggressiveness and decreased long-term survival of affected patients. To date, no information on cyclin B1 expression in renal cell cancer is available.…”

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confidence: 99%

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Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Ikuerowo

Kuczyk

Mengel

et al. 2006

Intl Journal of Cancer

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Cyclin B1, identified as a regulator of late cell cycle, is involved in the development and progression of a variety of human malignancies. To clarify the role of cyclin B1 in the pathogenesis and prognosis of renal cell carcinoma (RCC), protein expression was compared with clinicopathological characteristics of patients as well as the long-term survival after surgical therapy. Expression analysis was carried out by immunohistochemistry and tissue microarray analysis. The microarrays that represented the primary tumors, their invasion front and normal peritumoral renal parenchyma contained 753 tissue cores obtained from 251 randomly selected nephrectomy specimens. Immunopositivity within the primary tumors was significantly associated with tumor stage (pT) (p < 0.01), lymph node status (pN) (p < 0.01) as well as the presence of systemic metastatic disease (p 5 0.01). Subcellular expression in the cytoplasm of tumor cells significantly correlated with pT (p 5 0.02) and pN (p 5 0.03). When peritumoral tissue samples exhibited a relative amount of <10% of positively reacting epithelial cells, cyclin B positivity was identified to predict long-term survival of patients in univariate analysis (p < 0.01) whereas borderline significance was observed in multivariate statistical analysis (p 5 0.05). Increased intratumoral cyclin B1 positivity and aberrant localization of signals within the cytoplasm of tumor cells is positively correlated with the tendency towards tumor progression, indicating the significant role of cyclin B1 in the development and pathogenesis of RCC. The result of uni-and multivariate statistical analysis suggests the prognostic value of cyclin B1 for RCC patients. ' 2006 Wiley-Liss, Inc.Key words: renal cell carcinoma; cyclin B1; prognosis Renal cell carcinoma (RCC), accounts for 3% of human malignancies in western countries. 1 The incidence of RCC has increased during the past decades, at least in part due to the widespread availability of imaging modalities such as ultrasonography or computerized tomography during evaluation of abdominal and gastrointestinal complaints, thus resulting in a higher frequency of incidentally diagnosed, but still organ-confined tumors. 2 Though surgery offers the chance to cure localized disease, therapy for metastatic disease remains inadequate. 3 While RCC can be considered as widely resistant towards chemo-and radiotherapy, the application of systemic immunotherapy results in a limited and in most cases disappointing clinical response. However, both a better understanding of molecular processes involved in carcinogenesis 3 as well as the introduction of molecular-targeted agents are expected to improve the efficacy of future treatment modalities that can be offered to patients with metastasized RCC. [4][5][6][7][8][9] Uncontrolled cell division is one of the key features of tumor cells. Cyclins and cyclin-dependent kinases (cdk) play an important role in the passage of cells through the cell cycle. 10,11 The early phase of the cell cycle that includes the G1 and S ...

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 99%

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Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Ikuerowo

Kuczyk

Mengel

et al. 2006

Intl Journal of Cancer

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“…37 In the present study, Ki-67-positive cells generally paralleled cyclin B1-stained cells in individual tumors on serial sections, and statistical analysis also demonstrated a very close correlation between cyclin B1 and Ki-67 expressions either in the individual tumor categories or overall tumors (Po0.0001, r ¼ 0.742), suggesting that cyclin B1 is one of the key factors regulating cell proliferation in pulmonary neuroendocrine tumors, and that aberrant cyclin B1 expression may be critical for promoting cell cycle progression and unrestrained tumor cell proliferation. A recent study showed that Ki-67 played a role in the disintegration and reformation of nucleolus, and thereby in entry into and exit from the Mphase of the cell cycle depending on cyclin B1 expression.…”

Section: Discussionmentioning

confidence: 99%

Divergent cyclin B1 expression and Rb/p16/cyclin D1 pathway aberrations among pulmonary neuroendocrine tumors

et al. 2004

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A total of 111 pulmonary neuroendocrine tumors comprising 13 typical carcinoids, five atypical carcinoids, 44 large-cell neuroendocrine carcinomas and 49 small-cell carcinomas were immunohistochemically studied for dysregulated cyclin B1 expression and disruption of the Rb/p16/cyclin D1 pathway (Rb pathway), and the results were correlated with tumor proliferation activity and clinical outcome. Overexpression of cyclins B1 and D1, respectively, was detected in no and 15% typical carcinoids, 20 and 20% atypical carcinoids, 84 and 32% large-cell neuroendocrine carcinomas, 84 and 10% small-cell carcinomas. Loss of Rb and p16 expression, respectively, was observed in no and 14% typical carcinoids, no and 40% atypical carcinoids, 49 and 18% largecell neuroendocrine carcinomas, 84 and 8% small-cell carcinomas. In summary, 29% typical carcinoids, 20% atypical carcinoids, 78% large-cell neuroendocrine carcinomas and 93% small-cell carcinomas had Rb pathway aberrations. Rb pathway aberration was mostly attributed to Rb loss in small-cell carcinomas, while p16 loss and/or cyclin D1 overexpression besides Rb loss also played an important role in large-cell neuroendocrine carcinomas, while cyclin D1 overexpression was the only cause of Rb pathway aberration in carcinoid tumors. Thus, both cyclin B1-associated G2/M arrest and Rb-mediated G1 arrest are consistently compromised in highgrade large-cell neuroendocrine carcinoma and small-cell carcinoma, but are generally intact or occasionally altered in carcinoid tumor; the mechanisms involved in Rb pathway aberration among the tumor categories are different, reflecting a genetic divergence among the individual tumor categories. Cyclin B1 expression closely correlated with the Ki-67 labeling index either in the individual tumor categories or overall tumors (Po0.0001, r ¼ 0.742), suggesting that cyclin B1 is one of the key factors regulating cell proliferation in pulmonary neuroendocrine tumors. Neither cyclins B1 and D1, Rb, p16, nor Ki-67 correlated with patient survival in individual tumor categories, suggesting that the prognostic significance of these factors is tumor-type specific.

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“…Previous reports revealed that Cyclin B1 overexpression was observed in the cytoplasm of many cancers and related to prognosis (36,37). Korenaga et al showed the association between cyclin B1 and lymph node metastasis in human colorectal cancer (38). In gastric cancer, Yasuda et al reported that Cyclin B1 overexpression was closely associated with less aggressive tumor behavior, including nodal metastasis and stage of disease (39).…”

Section: Introductionmentioning

confidence: 99%

CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

Okayama

Kumamoto²,

Saitou³

et al. 2009

Oncol Rep

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Abstract. The aim of this study was to examine the expression of CD44v6, CD54, Cdx2, CXCL5, Cyclin B1, MMP-7, nm23, RCAS1 and Survivin in primary gastric cancer and to investigate whether these molecules were useful in predicting the lymph node status. They were selected as candidates for indicators of lymph node metastasis from various kinds of cancer-associated genes reported previously. In 135 cases of radically resected primary gastric adenocarcinoma, we investigated the association between the expression of these molecules and clinocopathologic factors by immunohistochemistry. The results revealed that the expression of CD44v6 and MMP-7 were significantly associated with lymph node status. By contrast, nuclear Cdx2 expression was found to be inversely correlated with lymph node metastasis. Moreover, multivariate analysis demonstrated that CD44v6, MMP-7 and nuclear Cdx2 were independent predictors for lymph node status. In conclusion, our results suggest that positive expression of both CD44v6 and MMP-7, and negative expression of nuclear Cdx2 may serve as powerful predictors of lymph node metastasis in gastric cancer. Combined evaluation of these markers could be further useful to predict lymph node status clinically.

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The relationship between cyclin B1 overexpression and lymph node metastasis in human colorectal cancer

Cited by 33 publications

References 20 publications

Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Alteration of subcellular and cellular expression patterns of cyclin B1 in renal cell carcinoma is significantly related to clinical progression and survival of patients

Divergent cyclin B1 expression and Rb/p16/cyclin D1 pathway aberrations among pulmonary neuroendocrine tumors

CD44v6, MMP-7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer

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