Pattern of invasion is of prognostic value in surgically treated cervical cancer patients

Horn, Lars‐Christian; Fischer, Uta; Raptis, Georgios; Bilek, K; Hentschel, Bettina; Richter, C. E.; Braumann, Ulf‐Dietrich; Einenkel, Jens

doi:10.1016/j.ygyno.2006.05.046

Cited by 39 publications

(55 citation statements)

References 19 publications

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“…Concurring with this, E-cadherin expression correlates negatively with progression of cervical intraepithelial neoplasia (Branca et al, 2006). Overall, these data together with previous observations that cervical tumors with a 'diffuse' invasive pattern are associated with a significant decrease in survival rates as compared with tumors with a more cohesive or 'pushing' pattern of invasion (Horn et al, 2006), strongly support the hypothesis that WIF1 blocks human cervical cancer progression, and its re-expression has the potential to change patient's prognosis.…”

Section: Wif1 Inhibits Cervical Cancer Growth and Invasion I Ramachansupporting

confidence: 78%

“…Vector-treated tumors were highly infiltrative, showing diffuse infiltration with single cell isolation. In patients, this 'spraylike' pattern is associated with advanced tumor stages, increased rate of recurrence and a reduced overall survival (Horn et al, 2006). In contrast, WIF1-treated tumors presented with well-defined cohesive or 'pushing' borders, a pattern associated with a very good prognostic outcome (Horn et al, 2006).…”

Section: Wif1 Inhibits Tumor Proliferation and Invasionmentioning

confidence: 99%

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Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo

et al. 2011

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Aberrant activation of Wingless-type (Wnt)/b-catenin signaling is widespread in human cervical cancer. However, the underlying mechanisms of Wnt activation and the therapeutic potential of Wnt inhibition remain largely unknown. Here, we demonstrate that the Wnt inhibitory factor 1 (WIF1), a secreted Wnt antagonist, is downregulated in all human primary cervical tumors and cell lines analyzed. Our data reveal that WIF1 downregulation occurs due to promoter hypermethylation and is an early event in cervical oncogenesis. WIF1 re-expression upon 5-aza-2 0 -deoxycytidine treatment or WIF1 gene transfer induces significant apoptosis and G 2 /M arrest, and inhibits cervical cancer cell proliferation in vitro. Consistent with this, treatment of established mice tumor xenografts with peritumoral WIF1 gene transfer results in a significant inhibition of cancer growth and invasion. WIF1 treatment causes a significant decrease in intracellular WNT1 and TCF-4 proteins revealing novel Wnt-regulatory mechanisms. Thus, WIF1 causes a major cellular re-distribution of b-catenin and a significant inhibition of the Wnt/b-catenin pathway in tumor cells, as documented by a remarkable reversion in the expression of Wnt/b-catenin transcriptional target genes (E-cadherin, c-Myc, cyclin D1, CD44 and VEGF). Consequently, multiple critical events in tumor progression and metastasis such as cell proliferation, angiogenesis and invasion were inhibited by WIF1. In addition, WIF1 modulated the expression of specific anti-apoptotic and apoptotic proteins, thereby inducing significant apoptosis in vivo. Our findings demonstrate for the first time that WIF1 downregulation by epigenetic gene silencing is an important mechanism of Wnt activation in cervical oncogenesis. Of major clinical relevance, we show that peritumoral WIF1 gene transfer reduces not only cancer growth but also invasion in well-established tumors. Therefore, our data provide novel mechanistic insights into the role of WIF1 in cervical cancer progression, and the important preclinical validation of WIF1 as a potent drug target in cervical cancer treatment.

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Section: Wif1 Inhibits Cervical Cancer Growth and Invasion I Ramachansupporting

confidence: 78%

Section: Wif1 Inhibits Tumor Proliferation and Invasionmentioning

confidence: 99%

Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo

et al. 2011

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“…Several pathologic features have been extensively studied and recognized as standard prognostic features such as extent of tumor invasion, presence of lymphovascular space invasion (LVSI), parametrial involvement, and lymph node metastasis (Biewenga et al, 2009;2011;Suprasert et al, 2010). The pathologic characteristics at the invasive margin (tumor front) were found to provide prognostic information in several types of cancers, including the uterine cervix (Bryne et al, 1998;Kristensen et al, 1999;Horn et al, 2006a;Eggen et al, 2007). The major characteristics of invasive margin include invasive pattern, stromal desmoplasia, and peritumoral inflammatory reaction (Horn et al, 2006a;2006b;Fregnani et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…The pathologic characteristics at the invasive margin (tumor front) were found to provide prognostic information in several types of cancers, including the uterine cervix (Bryne et al, 1998;Kristensen et al, 1999;Horn et al, 2006a;Eggen et al, 2007). The major characteristics of invasive margin include invasive pattern, stromal desmoplasia, and peritumoral inflammatory reaction (Horn et al, 2006a;2006b;Fregnani et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Model in Patients with Early-stage Squamous Cell Carcinoma of the Uterine Cervix: A Combination of Invasive Margin Pathological Characteristics and Lymphovascular Space Invasion

Khunamornpong

Lekawanvijit²,

Settakorn³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: This study aimed to develop a prognostic model in patients with early-stage cervical squamous cell carcinoma based on clinicopathological features, including invasive margin characteristics. Materials and Methods: Clinicopathological features and outcomes of 190 patients with FIGO stage IB-IIA cervical squamous cell carcinoma treated by surgery were collected and analyzed for factors associated with tumor recurrence. In addition to well-recognized pathological risk factors, the pathological characteristics of invasive margin (type of invasive pattern and degree of stromal desmoplasia and peritumoral inflammatory reaction) were also included in the analysis. Multiple scoring models were made by matching different clinicopathological variables and/ or different weighting of the score for each variable. The model with the best performance in the prediction of recurrence and decreased survival was selected. Results: The model with the best performance was composed of a combined score of invasive pattern, lymphovascular space invasion (LVSI), and degree of inflammatory reaction and stromal desmoplasia (total score =10). Compared to those with score ≤8, the patients with score 9-10 had a significantly higher recurrence rate in the overall group (p<0.001) and the subgroup without adjuvant therapy (p<0.001), while the significance was marginal in the subgroup with adjuvant therapy (p=0.069). In addition, the patients with score 9-10 had a higher rate of tumor recurrence at distant sites (p=0.007). The disease-free survival was significantly lower in the patients with score 9-10 than those with score ≤8 among the overall patients (p<0.001), in the subgroup without adjuvant therapy (p<0.001), and the subgroup with adjuvant therapy (p=0.047). Conclusions: In this study, a prognostic model based on a combination of pathological characteristics of invasive margin and LVSI proved to be predictive of tumor recurrence and decreased disease-free survival in patients with early-stage cervical squamous cell carcinoma.

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Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo

Sauer¹,

Grosser

Shahryari

et al. 2023

Advanced Science

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Cancer progression is caused by genetic changes and associated with various alterations in cell properties, which also affect a tumor's mechanical state. While an increased stiffness has been well known for long for solid tumors, it has limited prognostic power. It is hypothesized that cancer progression is accompanied by tissue fluidization, where portions of the tissue can change position across different length scales. Supported by tabletop magnetic resonance elastography (MRE) on stroma mimicking collagen gels and microscopic analysis of live cells inside patient derived tumor explants, an overview is provided of how cancer associated mechanisms, including cellular unjamming, proliferation, microenvironment composition, and remodeling can alter a tissue's fluidity and stiffness. In vivo, state‐of‐the‐art multifrequency MRE can distinguish tumors from their surrounding host tissue by their rheological fingerprints. Most importantly, a meta‐analysis on the currently available clinical studies is conducted and universal trends are identified. The results and conclusions are condensed into a gedankenexperiment about how a tumor can grow and eventually metastasize into its environment from a physics perspective to deduce corresponding mechanical properties. Based on stiffness, fluidity, spatial heterogeneity, and texture of the tumor front a roadmap for a prognosis of a tumor's aggressiveness and metastatic potential is presented.

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Pattern of invasion is of prognostic value in surgically treated cervical cancer patients

Cited by 39 publications

References 19 publications

Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo

Wnt inhibitory factor 1 induces apoptosis and inhibits cervical cancer growth, invasion and angiogenesis in vivo

Prognostic Model in Patients with Early-stage Squamous Cell Carcinoma of the Uterine Cervix: A Combination of Invasive Margin Pathological Characteristics and Lymphovascular Space Invasion

Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo

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