title: Immunohistochemical detection of lymph node-DTCs in patients with node-negative HNSCC.
abstract: This study was performed to systematically assess the prevalence, topography and prognostic impact of disseminated tumor cells (DTCs) in lymph nodes (LN) of patients with primary, regional and distant metastasis-free head and neck squamous cell carcinoma (HNSCC) who underwent resection with elective neck dissection. From the routinely processed resection specimen, we could prospectively analyze a total of 1.137 exactly mapped LNs of 50 pN0-HNSCC patients, classified as tumor free by routine histopathology. Three immunohistochemistry (IHC) assays using antibodies directed against CK5/14, a broad spectrum of CKs (1-8, 10, 14-16 and 19), and CD44v6, respectively, were applied on 4.190 LN sections to detect DTCs. The IHC results were correlated with clinicopathologic parameters and clinical follow-up data. We detected seven micrometastases (MM) in five patients and 31 DTCs in 12 patients. Overall, 15 (30%) patients were positive for DTCs or MMs. Strikingly, the anatomical distribution of LN affected with DTCs was not random, but was dependent on the lateralization of the primary tumor and clustered significantly most proximal to the primary tumor. None of the investigated patients developed loco-regional lymphatic or distant metastasis during the mean follow-up period of 71 months. Our results reveal clinically occult tumor cell dissemination as an early and frequent event in HNSCC. Considering that higher rates of recurrences in therapeutic LN dissection concepts have been reported than in elective neck dissection strategies, our DTC-data support to perform elective neck dissections, since they appear to be effective in preventing loco-regional lymphatic recurrence from LN DTCs or MMs.
authors.affiliation: Department of Oral-, Maxillo- and Plastic Facial Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sproll
authors.affiliation: Department of Oral-, Maxillo- and Plastic Facial Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Anna Karen
authors.initials: AK
authors.lastname: Freund
authors.affiliation: Department of Oral-, Maxillo- and Plastic Facial Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hassel
authors.affiliation: Department of Oral-, Maxillo- and Plastic Facial Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Marianne
authors.initials: M
authors.lastname: Hölbling
authors.affiliation: Department of Otorhinolaryngology, Protestant Hospital Bethesda, Duisburg, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Aust
authors.affiliation: Department of Otorhinolaryngology, Protestant Hospital Bethesda, Duisburg, Germany.
authors.forename: Sebastian H
authors.initials: SH
authors.lastname: Storb
authors.affiliation: Department of Oral-, Maxillo- and Plastic Facial Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Handschel
authors.affiliation: Department of Oral-, Maxillo- and Plastic Facial Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Teichmann
authors.affiliation: Department of Oral-, Maxillo- and Plastic Facial Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Depprich
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Behrens
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Rui Pedro Lousa
authors.initials: RP
authors.lastname: Neves
authors.affiliation: Department of Oral-, Maxillo- and Plastic Facial Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Norbert R
authors.initials: NR
authors.lastname: Kübler
authors.affiliation: Department of Pathology, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Kaiser
authors.affiliation: Institute of Pathology, Cytology and Molecular Pathology, Bergisch, Gladbach, Germany.
authors.forename: Stephan E
authors.initials: SE
authors.lastname: Baldus
authors.affiliation: Department of Pathology, Medical Faculty, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Csaba
authors.initials: C
authors.lastname: Tóth
authors.affiliation: Mathematical Institute, Heinrich-Heine-University of Düsseldorf, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kaisers
authors.affiliation: Department of General, Visceral and Pediatric Surgery, Medical Faculty, University Hospital of the Heinrich-Heine-University Düsseldorf, Germany.
authors.forename: Nikolas H
authors.initials: NH
authors.lastname: Stoecklein
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology / Q000302:isolation & purification; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000276:immunology / Q000473:pathology; D061206:Neoplasm Micrometastasis / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: C112697:CD44v6 antigen; D018960:Hyaluronan Receptors
keywords: lymph node disseminated tumor cells; lymphatic dissemination; micrometastasis; pN0-HNSCC; prognosis