title: Immunohistochemical markers of advanced basal cell carcinoma: CD56 is associated with a lack of response to vismodegib.
abstract: Vismodegib is an effective treatment for advanced basal cell carcinoma (BCC), but primary resistance to vismodegib remains to be elucidated. Alternative approaches are warranted to help selecting patients most likely to be responsive to treatment. The identification of immunohistochemical markers may support this perspective, as well as better understanding of resistance mechanisms. To determine the level of expression of CD56, PDGF-R, CD117, MMP9, TIMP3, and CXCR4 in advanced BCC, and explore whether expression levels are associated with non-response to vismodegib. A cross-sectional study was conducted. Immunohistochemical markers were selected based on their roles in tumour proliferation and/or migration in skin tumours. Tissue samples included pretreatment advanced BCC samples from patients treated with vismodegib, with an available response after six months of treatment. Regression optimised models were used to build hypotheses regarding a possible association between expression levels and non-response to vismodegib, which was then tested by logistic regression. Twenty-three patients were included. The percentage of samples expressing markers ranged from 43.5% (CD117) to 91.3% (CXCR4). CD56 expression was significantly associated with an increased risk of non-response to vismodegib (OR = 5.5; CI 95%: 3.4-29.8; p = 0.0488); a similar association was suggested for CXCR4 (p = 0.066), but not identified for other markers. These results provide a better understanding of the expression of immunohistochemical markers in advanced BCC. Further detailed analysis of CD56 expression may provide insights into guiding further investigation of the correlation between this marker and non-response to vismodegib.
authors.affiliation: Family Medicine Department, Nantes Medical School, 1 rue Gaston Veil 44035 Nantes.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Castillo
authors.affiliation: CRCNA, INSERM U892, CNRS 6299, 9 Quai Moncousu, 44093 Nantes.
authors.forename: Anne-Chantal
authors.initials: AC
authors.lastname: Knol
authors.affiliation: CRCNA, INSERM U892, CNRS 6299, 9 Quai Moncousu, 44093 Nantes,, PIMESP-SEB, Hôpital St Jacques, 85 rue St Jacques, 44093 Nantes.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Nguyen
authors.affiliation: CRCNA, INSERM U892, CNRS 6299, 9 Quai Moncousu, 44093 Nantes,, Dermato-Cancerology Department, CHU Hôtel-Dieu, 1 Place Alexis Ricordeau, 44093 Nantes.
authors.forename: Amir
authors.initials: A
authors.lastname: Khammari
authors.affiliation: Dermato-Cancerology Department, CHU Hôtel-Dieu, 1 Place Alexis Ricordeau, 44093 Nantes.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Saint-Jean
authors.affiliation: CRCNA, INSERM U892, CNRS 6299, 9 Quai Moncousu, 44093 Nantes,, Dermato-Cancerology Department, CHU Hôtel-Dieu, 1 Place Alexis Ricordeau, 44093 Nantes,, Unité de Thérapie Cellulaire et Génique (UTCG), CHU Hôtel-Dieu, 9 Quai Moncousu, 44093 Nantes, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Dreno
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis*; D002280:Basal Cell Carcinoma / Q000737:chemistry* / Q000188:drug therapy*; D003430:Cross-Sectional Studies; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D011725:Pyridines / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis; D012878:Skin Neoplasms / Q000737:chemistry* / Q000188:drug therapy*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000032:analysis; D017211:Treatment Failure
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D019002:CD56 Antigen; C527276:CXCR4 protein, human; C538724:HhAntag691; D011725:Pyridines; D019718:Receptors, CXCR4; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020780:Matrix Metalloproteinase 9
keywords: basal cell carcinoma; immunohistochemistry; treatment response; vismodegib