Prognostic Role of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Immunohistochemical Expression in Patients with R
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ORIGINAL ARTICLE
Prognostic Role of Aryl Hydrocarbon Receptor Interacting Protein (AIP) Immunohistochemical Expression in Patients with Resected Gastric Carcinomas Cristina Díaz del Arco 1,2 & Lourdes Estrada Muñoz 3 & Rodrigo Barderas Manchado 4 & Alberto Peláez García 5 & Luis Ortega Medina 1,2 & Elena Molina Roldán 2 & Guillermo Solís Fernández 4 & Soledad García Gómez de las Heras 3 & Mª Jesús Fernández Aceñero 1,6 Received: 25 May 2020 / Accepted: 23 June 2020 # Arányi Lajos Foundation 2020
Abstract Aryl hydrocarbon receptor (AHR) interacting protein (AIP) is a chaperone which binds to inactive AHR in the cell cytoplasm. AHR is best known for mediating the toxicity of halogenated aromatics, but it has also been linked to carcinogenesis and tumor progression in several tumor types. Our aims are to assess the features of AIP immunohistochemical (IHC) staining and to evaluate its possible role as a prognostic marker in gastric cancer (GC). Retrospective study of 147 cases of resected GC. Clinicopathological features were collected, tissue microarrays were constructed for AIP IHC and statistical analysis were performed. AIP staining was observed in 50.3% of tumors. All AIP-positive cases exhibited cytoplasmic or membranous staining, variably associated with nuclear co-staining. 93.2% of AIP-positive tumors showed AIP immunoreactivity in 100% of cells. Staining intensity was mild, moderate and intense in 33.8%, 13.5% and 52.7% of cases. Tumors were stratified according to AIP staining intensity into low expression (no or mild AIP immunoreactivity) and high expression (moderate or intense AIP immunoreactivity). 36.6% of our cases showed high AIP expression. High AIP expression was significantly and independently correlated to tumor progression and cancer death. Tumors with high AIP expression showed lower survival and higher progression rates. AIP expression might be useful for determining GC prognosis. More studies are needed to clarify the role of AHR pathway in GC, AIP expression and its potential use as a surrogate marker for selecting patients for AHR modulation therapy. Keywords Gastric cancer . Prognosis . Aryl hydrocarbon receptor interacting protein . AIP . Immunohistochemistry
Introduction Gastric cancer (GC) is the fifth most common malignant tumor in the world, and the third cause of cancer-related
* Cristina Díaz del Arco [email protected] 1
Complutense University of Madrid, Madrid Spain
2
Hospital Clínico San Carlos, Madrid, Spain
3
Rey Juan Carlos University, Madrid, Spain
4
Carlos III Health Institute (ISCIII), Madrid Spain
5
Hospital La Paz Institute for Health Research (IdiPAZ), Madrid, Spain
6
Hospital General Universitario Gregorio Marañón, Madrid, Spain
deaths [1]. In western countries, most patients are diagnosed at advanced stages, and the 5-year-survival rate is estimated to range between 10 and 30% [2, 3]. GC is a heterogeneous disease, both at the histological and molecular level, which occurs as a combination of environmental and genetic factors [4]. Several classificat
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