S‐phase fraction can predict event free survival in patients with pT2‐T3N0M0 colorectal carcinoma

Cascinu, Stefano; Ligi, M.; Graziano, Francesco; Ferro, Elena Del; Valentini, M.; Grianti, Cesare; Bartolucci, Marcello; Catalano, Giuseppina

doi:10.1002/(sici)1097-0142(19980915)83:6<1081::aid-cncr5>3.3.co;2-n

Cited by 4 publications

(6 citation statements)

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“…Our demonstration of an increased frequency of cyclin A‐positive cells in colonic adenomas and adenocarcinomas compared with normal colon parallels earlier flow cytometric evidence of increased numbers of S‐phase cells in colorectal adenocarcinoma 6–11 and combined in situ hybridization and immunohistochemical studies detecting histone H3 mRNA, a surrogate marker of S phase 37, and cyclin A expression 36. The proportion of total cells that are in the S phase in colorectal adenocarcinoma has been shown to be predictive of outcome and/or response to therapy 6–11, 36.…”

Section: Discussionsupporting

confidence: 85%

“…An accurate description of cell‐cycle parameters may be important in predicting the rate of growth, prognosis, and response to chemotherapy of colonic adenocarcinomas and may complement existing algorithms 7. An immunohistochemical method to estimate cell‐cycle phase distribution in situ would be of considerable value, in view of the difficulties in using flow cytometry in the routine diagnostic setting.…”

Section: Discussionmentioning

confidence: 99%

“…Estimating cell‐cycle phases can be used to predict clinical behaviour and response to chemotherapy in a variety of malignancies 3–5. In adenocarcinoma of the colorectum, the S‐phase fraction has been shown to relate strongly with outcome and to predict those patients most likely to respond to adjuvant chemotherapy 6–11.…”

Section: Introductionmentioning

confidence: 99%

“…Use of flow cytometry to analyse cell‐cycle phase in malignancy is well described 6–11. However, this approach has not entered routine clinical practice because of difficulties in the interpretation of flow cytometric data and the complexity of the equipment required to perform the analysis.…”

Section: Introductionmentioning

confidence: 99%

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A novel immunohistochemical method to estimate cell‐cycle phase distribution in archival tissue: implications for the prediction of outcome in colorectal cancer

Scott

Morris

Bird

et al. 2003

The Journal of Pathology

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An immunohistochemical method for assessing cell-cycle phase distribution in colorectal resection specimens would enable phase data to be incorporated into diagnostic algorithms for the estimation of prognosis and response to adjuvant chemotherapy in colorectal cancer. In contrast to flow cytometry, an immunohistochemical method would also allow the phase distribution to be examined within morphologically heterogeneous regions of neoplasms. Paraffin sections of normal colon (n = 25), colonic adenoma (n = 15), and colonic adenocarcinoma (n = 30) were analysed by immunohistochemistry using antibodies against markers of cell-cycle entry, Mcm-2 and Ki67, and putative markers of the cell-cycle phase, cyclins D1 and E (putative markers of G1 phase), cyclin A (S phase), cytoplasmic cyclin B1 (G2 phase), and phosphohistone H3 (M phase). The phase specificity of each marker was assessed by examining the degree of co-expression of adjacent phase markers using double-antibody fluorescence confocal microscopy and by comparison with flow cytometric analysis performed on adjacent tissue sections. The S-phase specificity of detectable cyclin A was also assessed in combination with in situ DNA replication using fluorescence confocal microscopy. All cells expressing phase markers co-expressed Mcm-2. Adjacent phase markers were not significantly co-expressed, confirming the relative specificity of these markers in tissue sections of colon. Cell-cycle phase distribution, calculated by immunohistochemistry, compared well with phase analyses obtained by flow cytometry. No cells expressed cyclin A in the absence of active DNA replication. The S-phase labelling index, as defined by detectable cyclin A expression, showed a positive correlation with the Mcm-2 labelling index and increased in the progression from normal colon to adenocarcinoma. In conclusion, a combination of these cell-cycle phase markers can be used to calculate the distribution of cells throughout each phase of the cell cycle in colorectal tissue sections. Detectable cyclin A can be used as a surrogate marker of S phase and may be of value in predicting prognosis and response to adjuvant therapy.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A novel immunohistochemical method to estimate cell‐cycle phase distribution in archival tissue: implications for the prediction of outcome in colorectal cancer

Scott

Morris

Bird

et al. 2003

The Journal of Pathology

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“…Numerous authors have reported new risk factors obtained by immunohistochemistry and molecular biology for recurrence in Stage II colon cancer patients, such as angiogenesis (vessel count, 9 vascular endo- thelial growth factor 10 ), nodal micrometastases (p53, 11 cytokeratin 12 ), immunohistochemical expression (p53, 13 c-erbB-2, 14 survivin 15 ), S-phase fraction, 26 and aneuploidy. 27 However, these factors usually need additional and expensive examination and have not been used in further clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Tumor Budding at the Invasive Margin Can Predict Patients at High Risk of Recurrence After Curative Surgery for Stage II, T3 Colon Cancer

Tanaka¹,

Hashiguchi²,

Ueno³

et al. 2003

Diseases of the Colon &Amp; Rectum

115

110

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Prognostic Variables for Cancer-Related Survival in Node-Negative Colorectal Carcinomas

Fabio¹,

Nascimbeni²,

Villanacci

et al. 2004

Dig Surg

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Background/Aim: The efficacy of adjuvant treatment in node-negative colorectal carcinoma is unproven. The purpose of this study was to analyze the prognostic value of routinely detectable clinicopathological variables in order to identify subgroups of node-negative colorectal cancer patients at a high risk of a recurrence. Methods: Seventy-three patients who did not receive radio- or chemotherapy were selected among 112 node-negative colorectal cancer patients who underwent curative resection. Follow-up was a minimum of 5 years or until death. The influence of 17 demographic, clinical, and pathological variables on the 5-year cancer-related survival was assessed using univariate and multivariate analyses. Results: The compliance with follow-up was 99%. The 5-year survival rate was 81%. Univariate analysis showed that T4 lesions (p < 0.001), age >70 years (p = 0.008), lymphatic invasion (p = 0.001), and neural invasion (p = 0.02) were significantly associated with a decreased survival. T4 stage (hazard ratio 12.75, p < 0.001) and age >70 (hazard ratio 3.08, p = 0.04) significantly affected the cancer-related survival on multivariate analysis. Conclusions: Node-negative colorectal cancer patients with T4 carcinoma or those aged over 70 years have a higher risk of recurrences after resection. They should receive adjuvant or neoadjuvant treatment compatible with their performance status.

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S‐phase fraction can predict event free survival in patients with pT2‐T3N0M0 colorectal carcinoma

Cited by 4 publications

References 0 publications

A novel immunohistochemical method to estimate cell‐cycle phase distribution in archival tissue: implications for the prediction of outcome in colorectal cancer

A novel immunohistochemical method to estimate cell‐cycle phase distribution in archival tissue: implications for the prediction of outcome in colorectal cancer

Tumor Budding at the Invasive Margin Can Predict Patients at High Risk of Recurrence After Curative Surgery for Stage II, T3 Colon Cancer

Prognostic Variables for Cancer-Related Survival in Node-Negative Colorectal Carcinomas

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