Is MIB-1 proliferation index a predictor for response to neoadjuvant therapy in patients with esophageal cancer?

Imdahl, A.; Jenkner, J; Ihling, Christian; Rückauer, K; Farthmann, E. H.

doi:10.1016/s0002-9610(00)00386-x

Cited by 23 publications

(13 citation statements)

References 20 publications

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“…37,38 However, low proliferation was also demonstrated to indicate reduced response to treatment, suggesting that tumors with elevated proliferation would have better response. 39 Moreover, according to recent studies, 40,41 in colorectal carcinoma a high Ki-67 value even constitutes a prognostic marker for low recurrence. We here provide an explanation for this apparent contradiction demonstrating that during proteolytic invasion the fraction of cycling cells depends on the balance between tumor cell proliferation, apoptosis, and stroma degradation.…”

Section: Discussionmentioning

confidence: 99%

Individual Cell-Based Models of Tumor-Environment Interactions

Galle

Sittig

Hanisch

et al. 2006

The American Journal of Pathology

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The presence of scattered tumor cells at the invading front of several carcinomas has clinical significance. These cells differ in their protein expression from cells in central tumor regions as recently shown for the EGF-TM7 receptor CD97. To understand the impact of such heterogeneity on tumor invasion, we investigated tumor cells with modified CD97 expression in vitro and in vivo. Applying an individual cellbased computer model approach, we linked specific cell properties of these cells to tumor invasion characteristics. CD97 overexpression promoted tumor growth in scid mice, stimulated single cell motility, increased proteolytic activity of matrix metalloproteinases, and secretion of chemokines in vitro in an isoform-specific manner. We demonstrated by computer simulation studies that these effects of CD97 can increase the invasion capacity of tumors. Furthermore, they can cause the appearance of scattered tumor cells at the invasion front. We identified local tumor environment interactions as triggers of these multiple capabilities. Experimentally, our simulation results are supported by the finding that CD97 expression in tumor cells is regulated by their environment. The progression of carcinomas is associated with a loss of epithelial differentiation and gain of mesenchyme-like capabilities of scattered tumor cells at the invasive front. This transition is associated with alterations of the expression of molecules involved in cell-cell and/or cell-extracellular matrix interactions, such as motility-promoting molecules.1-3 Furthermore, the secretion of cytokines and extracellular matrix-degrading proteinases are altered.4,5 For colorectal carcinomas it has been shown that in metastases such alterations are reversed and the molecules show a similar expression pattern or level compared with the central region of the primary tumor. 6,7 Consequently, Brabletz and co-workers 6,7 suggested an active role of the tumor environment in malignant tumor progression. A tumor microenvironment invasion model was suggested by Condeelis and co-workers. 8 It is a challenge to understand how the complex tumor invasion behavior emerges from collective interactions on the molecular and cellular level. Although the effects of molecular changes on the individual cell behavior can be quantified directly in experiments, dynamic links between the changes at the cellular level and the characteristics of the tumor invasion process are hard to assess. Here, we exclusively focus on that problem. A major insight into the link between individual cell behavior and tissue dynamics can be gained by computer modeling approaches. They permit investigation of the potential role of generic organization principles in specific tissues. We chose Supported by the Deutsche Forschungsgemeinschaft (DFG; project AU 132/3-1 and grant BIZ-6 1/1 to J.G.) and by the

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Section: Discussionmentioning

confidence: 99%

Individual Cell-Based Models of Tumor-Environment Interactions

Galle

Sittig

Hanisch

et al. 2006

The American Journal of Pathology

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“…However, on the basis of the present data, patients should not be excluded from further therapeutic intervention on the basis of information from OGD alone, as patients with potentially curable disease might be excluded. Newer techniques such as PET 18,20 and use of molecular markers 25,26 might improve the assessment of tumours as we move towards a treatment paradigm that excludes biologically unfavourable tumours from surgery.…”

Section: Discussionmentioning

confidence: 99%

Use of oesophagogastroscopy to assess the response of oesophageal carcinoma to neoadjuvant therapy

Brown

Thomas

Gotley

et al. 2003

British Journal of Surgery

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“…In esophageal cancers, it is reported that a pretreatment high Ki-67 index was significantly correlated with good response and prolonged survival of patients treated with neoadjuvant chemoradiotherapy followed by surgery. 36,37 In breast cancers, previous studies reported that reduction in the Ki-67 index during neoadjuvant chemotherapy significantly predicted the clinical response and was associated with better survival. In another study, a low Ki-67 proliferation index after neoadjuvant chemotherapy was the only significant predictor of better survival.…”

Section: Original Article 3330mentioning

confidence: 99%

Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy

Miyata

Yoshioka

Yamasaki

et al. 2009

Cancer

107

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BACKGROUND:In neoadjuvant chemotherapy for advanced esophageal cancers, complete tumor regression has been difficult to achieve, and tumor often remained after chemotherapy. However, the best method for evaluating the response to chemotherapy based on histopathologic examination of residual tumors has not been established.METHODS:Studied were 74 patients who received neoadjuvant chemotherapy (5‐fluorouracil, cisplatin, and doxorubicin), followed by surgery for advanced esophageal squamous cell carcinoma. The correlation between various histopathologic factors and clinical response with survival was examined, including the importance of tumor budding in the invasive front of tumors on clinical response and survival.RESULTS:Among 74 patients, 3 achieved a pathologic complete response, and 29 (41%) of 71 residual tumors demonstrated high‐grade budding in the invasive front. The 5‐year survival rate of patients with low‐grade budding tumors was 49%, compared with 17% for those with high‐grade budding (P < .001). Budding correlated inversely with good response, which was observed in 44 (60%) of 74 patients. Univariate analysis showed that pathologic tumor depth, number of lymph node metastases, pathologic stage, lymphatic invasion, budding and clinical response were significant prognostic factors. Multivariate analysis identified budding as the most important prognostic factor followed by number of lymph node metastases.CONCLUSIONS:The results of the current study indicated that tumor budding in the invasive front of tumors correlated significantly with clinical response and prognosis of patients with esophageal squamous cell carcinomas who received neoadjuvant chemotherapy. However, the mechanism of tumor budding in the invasion front of esophageal squamous cell carcinomas treated with chemotherapy was not clarified. Cancer 2009. © 2009 American Cancer Society.

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Is MIB-1 proliferation index a predictor for response to neoadjuvant therapy in patients with esophageal cancer?

Cited by 23 publications

References 20 publications

Individual Cell-Based Models of Tumor-Environment Interactions

Individual Cell-Based Models of Tumor-Environment Interactions

Use of oesophagogastroscopy to assess the response of oesophageal carcinoma to neoadjuvant therapy

Tumor budding in tumor invasive front predicts prognosis and survival of patients with esophageal squamous cell carcinomas receiving neoadjuvant chemotherapy

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