title: Identification of melanoma cells and lymphocyte subpopulations in lymph node metastases by FTIR imaging histopathology.
abstract: While early stages of melanoma are usually cured by surgery, metastatic melanomas are difficult to treat because the widely available options have low response rates. Careful and precise diagnosis and staging are essential to determine patient's risk and to select appropriate treatments. Fortunately, the recent progress in immunotherapy is very encouraging. In this context, it is important to characterize the intratumoral infiltration of immune cells in each patient, which is however not done routinely due to the lack of standardized methods. In this study, we used Fourier transform infrared (FTIR) imaging combined with multivariate statistical analyses to investigate non-metastatic and metastatic lymph nodes from melanoma patients. Our results show that the different cell types have different infrared spectral features allowing automated identification of these cell types. High recognition rates were obtained using a supervised partial least square discriminant analysis (PLS-DA) model. Melanoma cells were recognized with 87.1% sensitivity and 85.7% specificity, showing that FTIR spectroscopy has similar detection power as immunohistochemistry. Besides, FTIR imaging could also distinguish lymphocyte subpopulations (B and T cells). Finally, we investigated the changes in lymphocytes due to the presence of metastases. Interestingly, specific features of spectra of lymphocytes present in metastatic or tumor-free lymph nodes could be evidenced by PCA. A PLS-DA model was capable of predicting whether lymphocytes originated from invaded or non-invaded lymph nodes. These data demonstrate that FTIR imaging is capable to distinguish known and also novel biological features in human tissues, with potential practical relevance for histopathological diagnosis and biomarker assessment.
authors.affiliation: Laboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: noemwald@ulb.ac.be.
authors.forename: N
authors.initials: N
authors.lastname: Wald
authors.affiliation: Ludwig Center for Cancer Research, Department of Oncology CHUV, University of Lausanne, Lausanne, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Bordry
authors.affiliation: Ludwig Center for Cancer Research, Department of Oncology CHUV, University of Lausanne, Lausanne, Switzerland.
authors.forename: P G
authors.initials: PG
authors.lastname: Foukas
authors.affiliation: Ludwig Center for Cancer Research, Department of Oncology CHUV, University of Lausanne, Lausanne, Switzerland.
authors.forename: D E
authors.initials: DE
authors.lastname: Speiser
authors.affiliation: Laboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Goormaghtigh
mesh_terms: D006801:Humans; D008198:Lymph Nodes / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging / Q000473:pathology*; D008214:Lymphocytes / Q000737:chemistry / Q000473:pathology*; D008545:Melanoma / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology*; D061848:Optical Imaging / Q000379:methods; D012878:Skin Neoplasms / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D000096142:Cutaneous Malignant Melanoma
keywords: FTIR imaging; IR spectroscopy; Immune cells; Lymphocytes; Melanoma; Metastases