Annika Eurola, Ari Ristimäki, Harri Mustonen, Anna-Maria Nurmi, Jaana Hagström, Pauliina Kallio, Kari Alitalo, Caj Haglund, Hanna Seppänen
{"title":"β-catenin加PROX1免疫染色可对新辅助治疗胰腺癌的疾病进展和患者生存率进行分层。","authors":"Annika Eurola, Ari Ristimäki, Harri Mustonen, Anna-Maria Nurmi, Jaana Hagström, Pauliina Kallio, Kari Alitalo, Caj Haglund, Hanna Seppänen","doi":"10.3233/TUB-211581","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Wnt/β-catenin signaling is a highly conserved signaling pathway that regulates the transcription factor PROX1. The role of β-catenin and PROX1 in pancreatic cancer is ambiguous, as some studies have associated their expression with tumor regression and some with tumor progression.</p><p><strong>Objective: </strong>We have investigated their expression in surgically treated pancreatic cancer patients receiving neoadjuvant therapy (NAT), and patients treated upfront with surgery (US). We furthermore compared the expression of β-catenin and PROX1 between patients who had a good or poor response to NAT.</p><p><strong>Methods: </strong>We evaluated β-catenin and PROX1 expression through immunohistochemistry in 88 neoadjuvant and 144 upfront surgery patients by scoring the intensity of the immunopositivity as 0-3, corresponding to negative, weak, moderate, or strong. We developed a six-tier grading scheme for the neoadjuvant responses by analyzing the remaining tumor cells in surgical specimen histological sections.</p><p><strong>Results: </strong>Strong β-catenin immunopositivity associated with improved survival in the patients with good NAT-response (≤10% residual tumor cells) (Hazard ratio [HR] 0.26 95%, confidence interval [CI] 0.07-0.88 p = 0.030). Additionally, the combined moderate β-catenin and PROX1 expression associated with improved survival (HR 0.20 95% CI 0.05-0-76 p = 0.018) among the good responders. Among the patients with a poor NAT-response (> 10% residual tumor cells), both strong β-catenin immunopositivity and strong combined β-catenin and PROX1 associated with shorter survival (HR 2.03 95% CI 1.16-3.55 p = 0.013, and HR 3.1 95% CI 1.08-8.94 p = 0.03, respectively). PROX1 alone was not associated with survival.</p><p><strong>Conclusions: </strong>Strong β-catenin immunopositivity and combined strong or moderate β-catenin and PROX1 immunopositivity associated with improved survival among the good NAT-responders and worse survival among the poor NAT-responders.</p>","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":"69-84"},"PeriodicalIF":0.0000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"β-catenin plus PROX1 immunostaining stratifies disease progression and patient survival in neoadjuvant-treated pancreatic cancer.\",\"authors\":\"Annika Eurola, Ari Ristimäki, Harri Mustonen, Anna-Maria Nurmi, Jaana Hagström, Pauliina Kallio, Kari Alitalo, Caj Haglund, Hanna Seppänen\",\"doi\":\"10.3233/TUB-211581\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Wnt/β-catenin signaling is a highly conserved signaling pathway that regulates the transcription factor PROX1. The role of β-catenin and PROX1 in pancreatic cancer is ambiguous, as some studies have associated their expression with tumor regression and some with tumor progression.</p><p><strong>Objective: </strong>We have investigated their expression in surgically treated pancreatic cancer patients receiving neoadjuvant therapy (NAT), and patients treated upfront with surgery (US). We furthermore compared the expression of β-catenin and PROX1 between patients who had a good or poor response to NAT.</p><p><strong>Methods: </strong>We evaluated β-catenin and PROX1 expression through immunohistochemistry in 88 neoadjuvant and 144 upfront surgery patients by scoring the intensity of the immunopositivity as 0-3, corresponding to negative, weak, moderate, or strong. We developed a six-tier grading scheme for the neoadjuvant responses by analyzing the remaining tumor cells in surgical specimen histological sections.</p><p><strong>Results: </strong>Strong β-catenin immunopositivity associated with improved survival in the patients with good NAT-response (≤10% residual tumor cells) (Hazard ratio [HR] 0.26 95%, confidence interval [CI] 0.07-0.88 p = 0.030). Additionally, the combined moderate β-catenin and PROX1 expression associated with improved survival (HR 0.20 95% CI 0.05-0-76 p = 0.018) among the good responders. Among the patients with a poor NAT-response (> 10% residual tumor cells), both strong β-catenin immunopositivity and strong combined β-catenin and PROX1 associated with shorter survival (HR 2.03 95% CI 1.16-3.55 p = 0.013, and HR 3.1 95% CI 1.08-8.94 p = 0.03, respectively). 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引用次数: 0
摘要
背景：Wnt/β-catenin信号传导是一种高度保守的信号传导途径，它调控转录因子PROX1。β-catenin和PROX1在胰腺癌中的作用尚不明确，有些研究认为它们的表达与肿瘤消退有关，有些则与肿瘤进展有关：我们调查了接受新辅助治疗（NAT）的手术治疗胰腺癌患者和前期手术治疗（US）患者中这两种蛋白的表达情况。此外，我们还比较了对 NAT 反应良好或反应不佳的患者中 β-catenin 和 PROX1 的表达情况：我们通过免疫组化方法评估了 88 例新辅助治疗患者和 144 例前期手术患者的 β-catenin 和 PROX1 表达情况，将免疫阳性强度分为 0-3 级，分别对应阴性、弱、中度和强。通过分析手术标本组织切片中残留的肿瘤细胞，我们为新辅助治疗反应制定了六级分级方案：结果：强β-catenin免疫阳性与NAT反应良好（残留肿瘤细胞≤10%）的患者生存率提高有关（危险比[HR] 0.26 95%, 置信区间[CI] 0.07-0.88 p = 0.030）。此外，在反应良好的患者中，β-catenin 和 PROX1 的合并中度表达与生存率的改善有关（HR 0.20 95% CI 0.05-0-76 p = 0.018）。在NAT反应不佳（残留肿瘤细胞大于10%）的患者中，强β-catenin免疫阳性以及强β-catenin和PROX1联合表达与生存期缩短相关（分别为HR 2.03 95% CI 1.16-3.55 p = 0.013和HR 3.1 95% CI 1.08-8.94 p = 0.03）。仅PROX1与生存率无关：结论：强β-catenin免疫阳性以及强或中度β-catenin和PROX1联合免疫阳性与NAT反应良好者生存率的提高有关，而与NAT反应不良者生存率的降低有关。
β-catenin plus PROX1 immunostaining stratifies disease progression and patient survival in neoadjuvant-treated pancreatic cancer.
Background: Wnt/β-catenin signaling is a highly conserved signaling pathway that regulates the transcription factor PROX1. The role of β-catenin and PROX1 in pancreatic cancer is ambiguous, as some studies have associated their expression with tumor regression and some with tumor progression.
Objective: We have investigated their expression in surgically treated pancreatic cancer patients receiving neoadjuvant therapy (NAT), and patients treated upfront with surgery (US). We furthermore compared the expression of β-catenin and PROX1 between patients who had a good or poor response to NAT.
Methods: We evaluated β-catenin and PROX1 expression through immunohistochemistry in 88 neoadjuvant and 144 upfront surgery patients by scoring the intensity of the immunopositivity as 0-3, corresponding to negative, weak, moderate, or strong. We developed a six-tier grading scheme for the neoadjuvant responses by analyzing the remaining tumor cells in surgical specimen histological sections.
Results: Strong β-catenin immunopositivity associated with improved survival in the patients with good NAT-response (≤10% residual tumor cells) (Hazard ratio [HR] 0.26 95%, confidence interval [CI] 0.07-0.88 p = 0.030). Additionally, the combined moderate β-catenin and PROX1 expression associated with improved survival (HR 0.20 95% CI 0.05-0-76 p = 0.018) among the good responders. Among the patients with a poor NAT-response (> 10% residual tumor cells), both strong β-catenin immunopositivity and strong combined β-catenin and PROX1 associated with shorter survival (HR 2.03 95% CI 1.16-3.55 p = 0.013, and HR 3.1 95% CI 1.08-8.94 p = 0.03, respectively). PROX1 alone was not associated with survival.
Conclusions: Strong β-catenin immunopositivity and combined strong or moderate β-catenin and PROX1 immunopositivity associated with improved survival among the good NAT-responders and worse survival among the poor NAT-responders.
期刊介绍：
Tumor Biology is a peer reviewed, international journal providing an open access forum for experimental and clinical cancer research. Tumor Biology covers all aspects of tumor markers, molecular biomarkers, tumor targeting, and mechanisms of tumor development and progression.
Specific topics of interest include, but are not limited to:
Pathway analyses,
Non-coding RNAs,
Circulating tumor cells,
Liquid biopsies,
Exosomes,
Epigenetics,
Cancer stem cells,
Tumor immunology and immunotherapy,
Tumor microenvironment,
Targeted therapies,
Therapy resistance
Cancer genetics,
Cancer risk screening.
Studies in other areas of basic, clinical and translational cancer research are also considered in order to promote connections and discoveries across different disciplines.
The journal publishes original articles, reviews, commentaries and guidelines on tumor marker use. All submissions are subject to rigorous peer review and are selected on the basis of whether the research is sound and deserves publication.
Tumor Biology is the Official Journal of the International Society of Oncology and BioMarkers (ISOBM).
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