Mucins and Cytokeratins as Serum Tumor Markers in Breast Cancer

Nicolini, Andrea; Rossi, Giuseppe

doi:10.1007/978-94-017-7215-0_13

Cited by 13 publications

(11 citation statements)

References 129 publications

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“…These proteins maintain the overall structural integrity of epithelial cells and play a crucial role in tissue differentiation and specialization. CK expression has therefore been used as a marker of tissue differentiation, for example, to assess tumor malignancy (Barak, Goike, Panaretakis, & Einarsson, ; Moll, ; Nicolini, Ferrari, & Rossi, ) and progenitor cell activation. Immunostaining using a pan‐CK antibody showed that CKs were prominently expressed in the Abx mouse liver but were not expressed in the control mouse liver (Figure d).…”

Section: Resultsmentioning

confidence: 99%

Hepatic progenitor cell activation is induced by the depletion of the gut microbiome in mice

Wang

Sun

et al. 2019

MicrobiologyOpen

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The homeostasis of the gut microbiome is crucial for human health and for liver function. However, it has not been established whether the gut microbiome influence hepatic progenitor cells (HPCs). HPCs are capable of self‐renewal and differentiate into hepatocytes and cholangiocytes; however, HPCs are normally quiescent and are rare in adults. After sustained liver damage, a ductular reaction occurs, and the number of HPCs is substantially increased. Here, we administered five broad‐spectrum antibiotics for 14 days to deplete the gut microbiomes of male C57BL/6 mice, and we measured the plasma aminotransferases and other biochemical indices. The expression levels of two HPC markers, SRY‐related high mobility group‐box gene 9 (Sox9) and cytokeratin (CK), were also measured. The plasma aminotransferase activities were not affected, but the triglyceride, lactate dehydrogenase, low‐density lipoprotein, and high‐density lipoprotein concentrations were significantly altered; this suggests that liver function is affected by the composition of the gut microbiome. The mRNA expression of Sox9 was significantly higher in the treated mice than it was in the control mice (p < 0.0001), and a substantial expression of Sox9 and CK was observed around the bile ducts. The mRNA expression levels of proinflammatory factors (interleukin [IL]‐1β, IL‐6, tumor necrosis factor [TNF]‐α, and TNF‐like weak inducer of apoptosis [Tweak]) were also significantly higher in the antibiotic‐treated mice than the levels in the control mice. These data imply that the depletion of the gut microbiome leads to liver damage, negatively impacts the hepatic metabolism and function, and activates HPCs. However, the underlying mechanisms remain to be determined.

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Section: Resultsmentioning

confidence: 99%

Hepatic progenitor cell activation is induced by the depletion of the gut microbiome in mice

Wang

Sun

et al. 2019

MicrobiologyOpen

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“…Several studies have shown that elevation of serum tumour markers occurs significantly in advance of diagnosis of BC recurrence using radiodiagnostic methods (15,16). This is why some authors recommend the use of a combination of several tumour markers, especially CEA, CA 15-3 and cytokeratins, to increase the sensitivity of relapse detection, namely every 3 months after surgery during the first 5 years and every 6 months thereafter (17,18). Guidelines of the European Group on Tumour Markers and the National Academy of Clinical Biochemistry recommend the use of tumour markers for the diagnosis of early disease recurrences (19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Perioperative Tumour Marker Levels as Prognostic Factors for Surgical Treatment of Breast Cancer Liver Metastases

Třeška¹,

Topolčan²,

Zoubkova³

et al. 2018

Anticancer Res

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Abstract. Background RFS (p<0.04; p<0.01; p<0.02), while CA19-9 postoperative levels were significant for OS and RFS (p<0.03; p<0.01 Breast cancer (BC) represents the most frequent cancer worldwide among women and is one of the most frequent causes of death in this population. BC metastases either develop concomitantly with the primary BC or at different time intervals in more than 50% of women with BC. Breast cancer liver metastases (BCLM) in most women are associated with concurrent BC dissemination to the lungs and bones and these represent the only site of metastatic BC in 12-15% women. Although great progress has been made in the diagnosis and effective treatment of BC, metastases develop in 30% of women despite timely diagnosis and radical treatment (1, 2).Surgical treatment of BCLM is an important component of multimodal therapeutic approaches. However, its results remain suboptimal compared, for example, to patients with colorectal cancer liver metastases. In our view, one strategy that might improve the results of surgical management of BCLM is the search for early indicators of tumour dissemination or for prognostically high-risk patients.Tumour markers are general indicators used in monitoring and follow-up of patients. The most frequently used markers to monitor treatment efficacy and diagnose BCLM recurrence include mucins, such as carbohydrate antigen CA 19-9, cytokeratins such as tissue polypeptide antigen (TPA) and tissue-specific polypeptide antigen (TPS), proliferation markers such as thymidine kinase (TK) and carcinoembryonic antigen (CEA). However, no study regarding the prognostic significance of preoperative serum tumour marker levels in patients undergoing surgery for BCLM has been published to date, as far as we are aware.The aim of our retrospective study was to determine whether perioperative levels of clinically routinely used tumour markers influence overall survival (OS) and recurrence-free survival (RFS) of patients undergoing resection or thermoablative therapy for BCLM as part of a multimodal approach. Patients and MethodsFrom January 1, 2000 until January 1, 2018, a total of 32 women underwent surgery for BCLM at the Department of Surgery, University Hospital in Pilsen, Czech Republic. Surgery was indicated in women in a general good state of health from the aspect of surgery and those who had consented to undergo the proposed surgical procedure. Surgery was indicated only if the metastases were located solely within the liver parenchyma. Every patient underwent hybrid imaging using positron-emission tomography (PET) and computed tomography (CT) or PET and magnetic resonance imaging (MRI) before surgery. Another requirement was that the future liver remnant volume exceed 30% of the total liver volume. The average age of these women was 49.5±10.7 years. The primary BC types were: ductal in 20 cases, lobular in seven, erysipeloid in four, and sarcomatoid (spindle cell) carcinoma in one. The average interval between initial breast surgery and BCLM surgery was 4.7±3.7 years.

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“…Mucins are a family of high-molecular weight glycoproteins expressed/produced by epithelial cells (Nicolini, Ferrari, & Rossi, 2015). Members of this family are involved in breast cancer development and altered expression is associated with cancer progression (Nicolini et al, 2015).…”

Section: Approaches Used To Detect Metastatic Lesions (On a Clinicmentioning

confidence: 99%

“…Members of this family are involved in breast cancer development and altered expression is associated with cancer progression (Nicolini et al, 2015). Carbohydrate antigen 15.3 (CA15.3) is the most common member in this family and approved by FDA as a biomarker for breast cancer and some other malignancies such as ovarian cancer, endometrial carcinoma, and nonsmall-cell lung cancer (Molina et al, 2008; Moore et al, 2008; Nicolini et al, 2015). Geraghty et al demonstrated that the serum CA15.3 level was elevated in 50–80% of breast cancer patients with metastasis (Geraghty, Coveney, Sherry, O’Higgins, & Duffy, 1992).…”

Section: Approaches Used To Detect Metastatic Lesions (On a Clinicmentioning

confidence: 99%

Detecting Tumor Metastases

Menezes

Das

Minn

et al. 2016

Advances in Cancer Research

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Metastasis is the complex process by which primary tumor cells migrate and establish secondary tumors in an adjacent or distant location in the body. Early detection of metastatic disease and effective therapeutic options for targeting these detected metastases remain impediments to effectively treating patients with advanced cancers. If metastatic lesions are identified early, patients might maximally benefit from effective early therapeutic interventions. Further, monitoring patients whose primary tumors are effectively treated for potential metastatic disease onset is also highly valuable. Finally, patients with metastatic disease can be monitored for efficacy of specific therapeutic interventions through effective metastatic detection techniques. Thus, being able to detect and visualize metastatic lesions is key and provides potential to greatly improve overall patient outcomes. In order to achieve these objectives, researchers have endeavored to mechanistically define the steps involved in the metastatic process as well as ways to effectively detect metastatic progression. We presently overview various preclinical and clinical in vitro and in vivo assays developed to more efficiently detect tumor metastases, which provides the foundation for developing more effective therapies for this invariably fatal component of the cancerous process.

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Mucins and Cytokeratins as Serum Tumor Markers in Breast Cancer

Cited by 13 publications

References 129 publications

Hepatic progenitor cell activation is induced by the depletion of the gut microbiome in mice

Hepatic progenitor cell activation is induced by the depletion of the gut microbiome in mice

Perioperative Tumour Marker Levels as Prognostic Factors for Surgical Treatment of Breast Cancer Liver Metastases

Detecting Tumor Metastases

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