Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas
The tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibo...
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MDPI AG
2021-10-01
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| Series: | Journal of Personalized Medicine |
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| author | Antonio Pellino Stefano Brignola Erika Riello Monia Niero Sabina Murgioni Maria Guido Floriana Nappo Gianluca Businello Marta Sbaraglia Francesca Bergamo Gaya Spolverato Salvatore Pucciarelli Stefano Merigliano Pierluigi Pilati Francesco Cavallin Stefano Realdon Fabio Farinati Angelo Paolo Dei Tos Vittorina Zagonel Sara Lonardi Fotios Loupakis Matteo Fassan |
| author_facet | Antonio Pellino Stefano Brignola Erika Riello Monia Niero Sabina Murgioni Maria Guido Floriana Nappo Gianluca Businello Marta Sbaraglia Francesca Bergamo Gaya Spolverato Salvatore Pucciarelli Stefano Merigliano Pierluigi Pilati Francesco Cavallin Stefano Realdon Fabio Farinati Angelo Paolo Dei Tos Vittorina Zagonel Sara Lonardi Fotios Loupakis Matteo Fassan |
| author_sort | Antonio Pellino |
| collection | DOAJ |
| description | The tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibodies against this protein. CLDN18.2 is the dominant isoform of CLDN18 in normal gastric and gastric cancer tissues. In this work, we evaluated the immunohistochemical (IHC) profile of CLDN18 and its correlation with clinical and histopathological features including p53, E-cadherin, MSH2, MSH6, MLH1, PMS2, HER2, EBER and PD-L1 combined positive score, in a large real-world and mono-institutional series of advanced GCs (<i>n</i> = 280) and GECs (<i>n</i> = 70). The association of IHC results with survival outcomes was also investigated. High membranous CLDN18 expression (2+ and 3+ intensity ≥75%) was found in 117/350 (33.4%) samples analyzed. CLDN18 expression correlated with age <70 (<i>p</i> = 0.0035), positive EBV status (<i>p</i> = 0.002), high stage (III, IV) at diagnosis (<i>p</i> = 0.003), peritoneal involvement (<i>p</i> < 0.001) and lower incidence of liver metastases (<i>p</i> = 0.013). CLDN18 did not correlate with overall survival. The predictive value of response of CLDN18 to targeted agents is under investigation in several clinical trials and further studies will be needed to select patients who could benefit from these therapies. |
| first_indexed | 2024-03-10T05:22:54Z |
| format | Article |
| id | doaj.art-b46fe1fae9344ce2b6b50d9f95f3903c |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T05:22:54Z |
| publishDate | 2021-10-01 |
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| series | Journal of Personalized Medicine |
| spelling | doaj.art-b46fe1fae9344ce2b6b50d9f95f3903c2023-11-22T23:57:51ZengMDPI AGJournal of Personalized Medicine2075-44262021-10-011111109510.3390/jpm11111095Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction AdenocarcinomasAntonio Pellino0Stefano Brignola1Erika Riello2Monia Niero3Sabina Murgioni4Maria Guido5Floriana Nappo6Gianluca Businello7Marta Sbaraglia8Francesca Bergamo9Gaya Spolverato10Salvatore Pucciarelli11Stefano Merigliano12Pierluigi Pilati13Francesco Cavallin14Stefano Realdon15Fabio Farinati16Angelo Paolo Dei Tos17Vittorina Zagonel18Sara Lonardi19Fotios Loupakis20Matteo Fassan21Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 35128 Padua, Italy Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35122 Padua, Italy Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35122 Padua, ItalyDepartment of Pathology, Azienda ULSS 2 Marca Trevigiana, 31100 Treviso, ItalyOncology Unit 1, Department of Oncology, Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 35128 Padua, Italy Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35122 Padua, ItalyOncology Unit 1, Department of Oncology, Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 35128 Padua, Italy Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35122 Padua, Italy Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35122 Padua, ItalyOncology Unit 1, Department of Oncology, Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 35128 Padua, Italy1st Surgery Unit, Department of Surgical, Oncological, and Gastroenterological Sciences (DISCOG), University of Padua, 35122 Padua, Italy1st Surgery Unit, Department of Surgical, Oncological, and Gastroenterological Sciences (DISCOG), University of Padua, 35122 Padua, Italy3rd Surgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, 35122 Padua, ItalySurgery Unit, Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 31033 Castelfranco Veneto, ItalyIndependent Statistician, 36020 Solagna, ItalyGastroenterology Unit, Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 35128 Padua, ItalyGastroenterology Unit, Department of Surgical, Oncological, and Gastroenterological Sciences (DISCOG), University of Padua, 35122 Padua, Italy Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35122 Padua, ItalyOncology Unit 1, Department of Oncology, Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 35128 Padua, ItalyOncology Unit 3, Department of Oncology, Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 35128 Padua, ItalyOncology Unit 1, Department of Oncology, Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 35128 Padua, Italy Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua, 35122 Padua, ItalyThe tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibodies against this protein. CLDN18.2 is the dominant isoform of CLDN18 in normal gastric and gastric cancer tissues. In this work, we evaluated the immunohistochemical (IHC) profile of CLDN18 and its correlation with clinical and histopathological features including p53, E-cadherin, MSH2, MSH6, MLH1, PMS2, HER2, EBER and PD-L1 combined positive score, in a large real-world and mono-institutional series of advanced GCs (<i>n</i> = 280) and GECs (<i>n</i> = 70). The association of IHC results with survival outcomes was also investigated. High membranous CLDN18 expression (2+ and 3+ intensity ≥75%) was found in 117/350 (33.4%) samples analyzed. CLDN18 expression correlated with age <70 (<i>p</i> = 0.0035), positive EBV status (<i>p</i> = 0.002), high stage (III, IV) at diagnosis (<i>p</i> = 0.003), peritoneal involvement (<i>p</i> < 0.001) and lower incidence of liver metastases (<i>p</i> = 0.013). CLDN18 did not correlate with overall survival. The predictive value of response of CLDN18 to targeted agents is under investigation in several clinical trials and further studies will be needed to select patients who could benefit from these therapies.https://www.mdpi.com/2075-4426/11/11/1095CLDN18.2gastric adenocarcinomabiomarkersimmunohistochemistry |
| spellingShingle | Antonio Pellino Stefano Brignola Erika Riello Monia Niero Sabina Murgioni Maria Guido Floriana Nappo Gianluca Businello Marta Sbaraglia Francesca Bergamo Gaya Spolverato Salvatore Pucciarelli Stefano Merigliano Pierluigi Pilati Francesco Cavallin Stefano Realdon Fabio Farinati Angelo Paolo Dei Tos Vittorina Zagonel Sara Lonardi Fotios Loupakis Matteo Fassan Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas Journal of Personalized Medicine CLDN18.2 gastric adenocarcinoma biomarkers immunohistochemistry |
| title | Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas |
| title_full | Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas |
| title_fullStr | Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas |
| title_full_unstemmed | Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas |
| title_short | Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas |
| title_sort | association of cldn18 protein expression with clinicopathological features and prognosis in advanced gastric and gastroesophageal junction adenocarcinomas |
| topic | CLDN18.2 gastric adenocarcinoma biomarkers immunohistochemistry |
| url | https://www.mdpi.com/2075-4426/11/11/1095 |
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