Diagnostic and Predictive Tissue Markers in GI Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Causes, Screening and Diagnosis".

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 16033

Special Issue Editor


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Guest Editor
Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
Interests: histopathology; GI and liver pathology; molecular biology; neoangiogenesis; transplant pathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

The recent advancements in systemic targeted therapies for cancer have not only made necessary the identification of new diagnostic and predictive tissue markers for different malignant neoplasms but also the need to offer the best standardization for immunohistochemical and molecular biology techniques. Histopathology and molecular pathology units can and must provide real indications for patients’ prognosis and best therapeutic options.

The aim of this Special Issue is to focus on the identification, feasibility, and reproducibility of recent tissue markers in GI tumors. The Special Issue, launched by Cancers, is dedicated to answering diagnostic and biological unsolved questions in GI cancers. Researchers are also encouraged to submit original research on new insights for known and well-established markers in the pathological mechanisms and molecular pathways of neoplasms of the GI tract, pancreas, liver, and biliary tract. Review articles describing the state of the art and systematic reviews on this topic are also encouraged. The main areas of interest are:

  • GI tract tumors
  • Pancreatic tumors
  • Liver tumors
  • Biliary tract tumors

Dr. Francesco Vasuri
Guest Editor

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Keywords

  • GI tract
  • histopathology
  • molecular pathology
  • liver and bile ducts
  • pancreas

Published Papers (7 papers)

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Editorial

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3 pages, 196 KiB  
Editorial
Special Issue: Diagnostic and Predictive Tissue Markers in G.I. Cancers
by Stefano Chillotti and Francesco Vasuri
Cancers 2023, 15(4), 1329; https://doi.org/10.3390/cancers15041329 - 20 Feb 2023
Viewed by 1105
Abstract
The compelling advancements in systemic targeted therapies for cancer drastically changed the role of histopathological analyses in recent decades [...] Full article
(This article belongs to the Special Issue Diagnostic and Predictive Tissue Markers in GI Cancers)

Research

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17 pages, 2722 KiB  
Article
Tensin2 Is a Novel Diagnostic Marker in GIST, Associated with Gastric Location and Non-Metastatic Tumors
by Sami Salmikangas, Tom Böhling, Nanna Merikoski, Joanna Jagdeo, Mika Sampo, Tiina Vesterinen and Harri Sihto
Cancers 2022, 14(13), 3212; https://doi.org/10.3390/cancers14133212 - 30 Jun 2022
Cited by 4 | Viewed by 2158
Abstract
GIST is a rare soft tissue sarcoma, for which KIT and DOG1 are used as highly sensitive diagnostic markers. Other diagnostic markers include CD34, protein kinase C θ, deficiency of succinate dehydrogenase complex subunit B, carbonic anhydrase II, and type I insulin-like growth [...] Read more.
GIST is a rare soft tissue sarcoma, for which KIT and DOG1 are used as highly sensitive diagnostic markers. Other diagnostic markers include CD34, protein kinase C θ, deficiency of succinate dehydrogenase complex subunit B, carbonic anhydrase II, and type I insulin-like growth factor receptor. We investigated the role of TNS2 as a diagnostic biomarker by using immunohistochemistry in 176 GISTs and 521 other sarcomas. All GISTs expressed TNS2, with intermediate or high expression in 71.4% of samples. The majority (89.8%) of other sarcomas were negative for TNS2, and intermediate to strong staining was only seen in 2.9% of samples. Strong TNS2 staining was associated with gastric location (gastric 52.8% vs. non-gastric 7.2%; p < 0.001), absence of metastases (non-metastatic tumors 44.3% vs. metastatic tumors 5.9%; p = 0.004), female sex (female 45.9% vs. male 33.8%; p = 0.029), and tumors of lower risk categories (very low or low 46.9% vs. intermediate 51.7% vs. high 29.0%; p = 0.020). TNS2 expression did not correlate with overall survival or metastasis-free survival. No associations between TNS2 expression and KIT/PDGFRA mutation status, tumor size, mitotic count, or age of the patient were detected. The results provide conclusive evidence for the value of TNS2 as a sensitive and specific diagnostic biomarker for GIST. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Tissue Markers in GI Cancers)
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14 pages, 20122 KiB  
Article
Evaluation of the Cell Block Method Using Overnight-Stored Bile for Malignant Biliary Stricture Diagnosis
by Mitsuru Okuno, Tsuyoshi Mukai, Keisuke Iwata, Naoki Watanabe, Takuji Tanaka, Taisei Iwasa, Kota Shimojo, Yosuke Ohashi, Akihiro Takagi, Yuki Ito, Ryuichi Tezuka, Shota Iwata, Yuhei Iwasa, Takahiro Kochi, Tomio Ogiso, Hideki Hayashi, Akihiko Sugiyama, Youichi Nishigaki and Eiichi Tomita
Cancers 2022, 14(11), 2701; https://doi.org/10.3390/cancers14112701 - 30 May 2022
Cited by 1 | Viewed by 1636
Abstract
The specimen collection and subsequent pathological diagnosis of malignant biliary stricture (MBS) are difficult. This study aimed to determine whether the cell block (CB) method using overnight-stored bile is useful in the diagnosis of MBS. This trial was a single-arm prospective study involving [...] Read more.
The specimen collection and subsequent pathological diagnosis of malignant biliary stricture (MBS) are difficult. This study aimed to determine whether the cell block (CB) method using overnight-stored bile is useful in the diagnosis of MBS. This trial was a single-arm prospective study involving a total of 59 patients with suspected MBS. The primary endpoint was cancer detectability and accuracy using the CB method, and a comparison with the detectability and accuracy achieved with bile cytology was made. The immunohistochemical sensitivity for maspin and p53 was also investigated in the CB and surgical specimens. We were able to collect bile from all 59 patients, and 45 of these patients were clinically diagnosed with MBS. The cancer detectability using the CB method (62.2%) was significantly higher than that using cytology (37.8%) (p = 0.0344). When CB was combined with biopsy, the rates of cancer detectability (75.6%) and accuracy (81.4%) increased. In eight patients who received surgical therapy, maspin- and p53-immunohistochemistry was applied to the surgical and CB specimens, and cancer cells in both specimens showed positive cytoplasmic and nuclear staining for maspin and nuclear staining for p53. The CB method is, thus, useful for detecting malignancy (UMIN000034707). Full article
(This article belongs to the Special Issue Diagnostic and Predictive Tissue Markers in GI Cancers)
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13 pages, 973 KiB  
Article
Clinical Significance of Telomerase Reverse-Transcriptase Promoter Mutations in Hepatocellular Carcinoma
by Francesca Pezzuto, Francesco Izzo, Pasquale De Luca, Elio Biffali, Luigi Buonaguro, Fabiana Tatangelo, Franco Maria Buonaguro and Maria Lina Tornesello
Cancers 2021, 13(15), 3771; https://doi.org/10.3390/cancers13153771 - 27 Jul 2021
Cited by 8 | Viewed by 2204
Abstract
Telomerase reactivation during hepatocarcinogenesis is recurrently caused by two point mutations occurring most frequently at the nucleotide −124 (95%) and occasionally at the nucleotide −146 (<5%) upstream of the TERT translational start site in hepatocellular carcinoma (HCC). In this study, we designed a [...] Read more.
Telomerase reactivation during hepatocarcinogenesis is recurrently caused by two point mutations occurring most frequently at the nucleotide −124 (95%) and occasionally at the nucleotide −146 (<5%) upstream of the TERT translational start site in hepatocellular carcinoma (HCC). In this study, we designed a droplet digital PCR (ddPCR) assay to detect TERT promoter (TERTp) nucleotide change G>A at position −124 and to quantify the mutant allele frequency (MAF) in 121 primary liver cancers, including 114 HCC along with 23 autologous cirrhotic tissues, five cholangiocarcinoma (CC), and two hepato-cholangiocarcinoma (HCC-CC). All cases were evaluated for tumour markers such as α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). We compared the sensitivity of ddPCR and Sanger sequencing and investigated the prognostic relevance of TERTp mutations. The TERTp G>A transition was identified in 63.6% and 52.1% of HCC samples by ddPCR and Sanger sequencing, respectively. One out of 23 (4.3%) peri-tumour tissues tested positive only by ddPCR. One out of five CC (20%) and none of the HCC-CC were found concordantly mutated by the two methods. The TERTp MAF ranged from 2% to 66%, and the large majority (85.5%) of mutated samples showed a value above 20%. A statistically significant correlation was found between TERTp mutation and tumour size (p = 0.048), while an inverse correlation was observed with CA19-9 levels (p = 0.0105). Moreover, HCC patients with TERTp −124A had reduced survival. In conclusion, the single nucleotide variation G>A at position −124 in TERTp, detected either by ddPCR or by Sanger sequencing, showed a remarkable high frequency in HCC. Such mutation is associated with lower levels of CA19-9 and reduced survival in HCC patients suggesting that the TERTp status may represent a distinct signature of liver cancer subgroups. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Tissue Markers in GI Cancers)
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Review

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24 pages, 1674 KiB  
Review
Clinical Applications of Classical and Novel Biological Markers of Pancreatic Cancer
by Leonel Pekarek, Oscar Fraile-Martinez, Cielo Garcia-Montero, Miguel A. Saez, Ines Barquero-Pozanco, Laura del Hierro-Marlasca, Patricia de Castro Martinez, Adoración Romero-Bazán, Miguel A. Alvarez-Mon, Jorge Monserrat, Natalio García-Honduvilla, Julia Buján, Melchor Alvarez-Mon, Luis G. Guijarro and Miguel A. Ortega
Cancers 2022, 14(8), 1866; https://doi.org/10.3390/cancers14081866 - 7 Apr 2022
Cited by 8 | Viewed by 2466
Abstract
The incidence and prevalence of pancreatic adenocarcinoma have increased in recent years. Pancreatic cancer is the seventh leading cause of cancer death, but it is projected to become the second leading cause of cancer-related mortality by 2040. Most patients are diagnosed in an [...] Read more.
The incidence and prevalence of pancreatic adenocarcinoma have increased in recent years. Pancreatic cancer is the seventh leading cause of cancer death, but it is projected to become the second leading cause of cancer-related mortality by 2040. Most patients are diagnosed in an advanced stage of the disease, with very limited 5-year survival. The discovery of different tissue markers has elucidated the underlying pathophysiology of pancreatic adenocarcinoma and allowed stratification of patient risk at different stages and assessment of tumour recurrence. Due to the invasive capacity of this tumour and the absence of screening markers, new immunohistochemical and serological markers may be used as prognostic markers for recurrence and in the study of possible new therapeutic targets because the survival of these patients is low in most cases. The present article reviews the currently used main histopathological and serological markers and discusses the main characteristics of markers under development. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Tissue Markers in GI Cancers)
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15 pages, 4067 KiB  
Review
Locoregional Treatments in Cholangiocarcinoma and Combined Hepatocellular Cholangiocarcinoma
by Matteo Renzulli, Daryl Ramai, Jameel Singh, Samridhi Sinha, Nicolò Brandi, Anna Maria Ierardi, Elisa Albertini, Rodolfo Sacco, Antonio Facciorusso and Rita Golfieri
Cancers 2021, 13(13), 3336; https://doi.org/10.3390/cancers13133336 - 2 Jul 2021
Cited by 24 | Viewed by 3221
Abstract
Cholangiocarcinoma (CCA) is a primary and aggressive cancer of the biliary tree. Combined hepatocellular cholangiocarcinoma (CHC) is a distinctive primary liver malignancy which has properties of both hepatocytic and cholangiocytic differentiation. CHC appears to have a worse prognosis compared to hepatocellular carcinoma, and [...] Read more.
Cholangiocarcinoma (CCA) is a primary and aggressive cancer of the biliary tree. Combined hepatocellular cholangiocarcinoma (CHC) is a distinctive primary liver malignancy which has properties of both hepatocytic and cholangiocytic differentiation. CHC appears to have a worse prognosis compared to hepatocellular carcinoma, and similar to that of intrahepatic CCA. While significant advances have been made in understanding the pathophysiology and treatment of these two tumor types, their prognosis remains poor. Currently, liver resection is the primary treatment modality; however, only a minority of patients are eligible for surgery. However, the use of locoregional therapies proves an alternative approach to treating locally advanced disease with the aim of converting to resectability or even transplantation. Locoregional therapies such as transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT), radiofrequency ablation (RFA), and photodynamic therapy (PDT) can provide patients with tumor control and increase the chances of survival. In this review, we appraise the evidence surrounding the use of locoregional therapies in treating patients with CCA and CHC. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Tissue Markers in GI Cancers)
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Other

24 pages, 2973 KiB  
Systematic Review
Neuropilin-1 as a Potential Biomarker of Prognosis and Invasive-Related Parameters in Liver and Colorectal Cancer: A Systematic Review and Meta-Analysis of Human Studies
by Paula Fernández-Palanca, Tania Payo-Serafín, Flavia Fondevila, Carolina Méndez-Blanco, Beatriz San-Miguel, Marta R. Romero, María J. Tuñón, Jose J. G. Marin, Javier González-Gallego and José L. Mauriz
Cancers 2022, 14(14), 3455; https://doi.org/10.3390/cancers14143455 - 15 Jul 2022
Cited by 7 | Viewed by 2183
Abstract
Neuropilin-1 (NRP1) is a transmembrane protein involved in numerous cellular functions which has had increasing interest from cancer researchers. Liver cancer and colorectal cancer (CRC) are two of the most frequent and deadly tumors with a complex pharmacological framework. Here, we assessed the [...] Read more.
Neuropilin-1 (NRP1) is a transmembrane protein involved in numerous cellular functions which has had increasing interest from cancer researchers. Liver cancer and colorectal cancer (CRC) are two of the most frequent and deadly tumors with a complex pharmacological framework. Here, we assessed the prognostic, diagnostic and clinicopathological value of NRP1 in liver cancer and CRC patients. We searched PubMed, Scopus, Web of Science, Embase and Cochrane Library databases for articles evaluating the NRP1 correlation with survival parameters, tumor development or clinicopathological features. Hazard ratios and odds ratios with 95% confidence intervals were extracted or estimated by Parmar method and pooled to evaluate the overall effect size with STATA 16 software. Heterogeneity was analyzed by chi-square-based Q test and I2 statistic, along with meta-regression and subgroup analysis, and publication bias was assessed by funnel plot asymmetry and Egger’s test. The study protocol was registered in PROSPERO (CRD42022307062). NRP1 overexpression was significantly correlated with lower survival in liver cancer patients and with tumor development in hepatocarcinoma patients, and was strongly correlated with an increased risk of vascular invasion in liver cancer and metastasis in CRC and liver tumors. These results support the role of NRP1 as a potential and useful biomarker in both types of cancer. Full article
(This article belongs to the Special Issue Diagnostic and Predictive Tissue Markers in GI Cancers)
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