title: Correlation of a priori DCE-MRI and (1)H-MRS data with molecular markers in neck nodal metastases: Initial analysis.
abstract: The aim of the present study is to correlate non-invasive, pretreatment biological imaging (dynamic contrast enhanced-MRI [DCE-MRI] and proton magnetic resonance spectroscopy [(1)H-MRS]) findings with specific molecular marker data in neck nodal metastases of head and neck squamous cell carcinoma (HNSCC) patients. Pretreatment DCE-MRI and (1)H-MRS were performed on neck nodal metastases of 12 patients who underwent surgery. Surgical specimens were analyzed with immunohistochemistry (IHC) assays for: Ki-67 (reflecting cellular proliferation), vascular endothelial growth factor (VEGF) (the "endogenous marker" of tumor vessel growth), carbonic anhydrase (CAIX), hypoxia inducible transcription factor (HIF-1α), and human papillomavirus (HPV). Additionally, necrosis was estimated based on H&E staining. The Spearman correlation was used to compare DCE-MRI, (1)H-MRS, and molecular marker data. A significant correlation was observed between DCE-MRI parameter std(k(ep)) and VEGF IHC expression level (rho=0.81, p=0.0001). Furthermore, IHC expression levels of Ki-67 inversely correlated with std(K(trans)) and std(v(e)) (rho=-0.71; p=0.004, and rho=-0.73; p=0.003, respectively). Other DCE-MRI, (1)H-MRS and IHC values did not show significant correlation. The results of this preliminary study indicate that the level of heterogeneity of perfusion in metastatic HNSCC seems positively correlated with angiogenesis, and inversely correlated with proliferation. These results are preliminary in nature and are indicative, and not definitive, trends portrayed in HNSCC patients with nodal disease. Future studies with larger patient populations need to be carried out to validate and clarify our preliminary findings.
authors.affiliation: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Jacobus F A
authors.initials: JF
authors.lastname: Jansen
authors.forename: Diane L
authors.initials: DL
authors.lastname: Carlson
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Lu
authors.forename: Hilda E
authors.initials: HE
authors.lastname: Stambuk
authors.forename: Andre L
authors.initials: AL
authors.lastname: Moreira
authors.forename: Bhuvanesh
authors.initials: B
authors.lastname: Singh
authors.forename: Snehal G
authors.initials: SG
authors.lastname: Patel
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Kraus
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wong
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Shaha
authors.forename: Jatin P
authors.initials: JP
authors.lastname: Shah
authors.forename: Amita
authors.initials: A
authors.lastname: Shukla-Dave
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000378:metabolism / Q000556:secondary; D003287:Contrast Media; D005260:Female; D052162:Human papillomavirus 16 / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D009333:Neck; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D042461:Vascular Endothelial Growth Factor A; D002256:Carbonic Anhydrases