Predictability of Recurrence using Immunohistochemistry to delineate Surgical Margins in mucosal Head and Neck Squamous Cell Carcinoma (PRISM-HNSCC): study protocol for a prospective, observational and bilateral study in Australia and India

Abstract

ObjectivesTreatment failure and poor 5-year survival in mucosal head and neck squamous cell carcinoma (HNSCC) has remained unchanged for decades mainly due to advanced stage of presentation and high rates of recurrence. Incomplete surgical removal of the tumour, attributed to lack of reliable methods to delineate the surgical margins, is a major cause of disease recurrence. The predictability of recurrence using immunohistochemistry (IHC) to delineate surgical margins (PRISM) in mucosal HNSCC study aims to redefine margin status by identifying the true extent of the tumour at the molecular level by performing IHC with molecular markers, eukaryotic initiation factor, eIF4Eand tumour suppressor gene, p53, on the surgical margins and test the use of Lugol’s iodine and fluorescence visualisation prior to the wide local excision. This article describes the study protocol at its pre - results stage.Methods and analysisPRISM-HNSCC is a bilateral observational research being conducted in Darwin, Australia and Vellore, India. Individuals diagnosed with HNSCC will undergo the routine wide local excision of the tumour followed by histopathological assessment. Tumours with clear surgical margins that satisfy the exclusion criteria will be selected for further staining of the margins with eIF4E and p53 antibodies. Results of IHC staining will be correlated with recurrences in an attempt to predict the risk of disease recurrence. Patients in Darwin will undergo intraoperative staining of the lesion with Lugol’s iodine and fluorescence visualisation to delineate the excision margins while patients in Vellore will not undertake these tests. The outcomes will be analysed.Ethics and disseminationThe PRISM-HNSCC study was approved by the institutional ethics committees in Darwin (Human Research Ethics Committee 13-2036) and Vellore (Institutional Review Board Min. no. 8967). Outcomes will be disseminated through publications in academic journals and presentations at educational meetings and conferences. It will be presented as dissertation at the Charles Darwin University. We will communicate the study results to both participating sites. Participating sites will communicate results with patients who have indicated an interest in knowing the results.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12616000715471).

Pilot study of loss of the p53/p63 target gene PERP at the surgical margin as a potential predictor of local relapse in head and neck squamous cell carcinoma

“…Expression of both p53 and eIF4E in basal epithelial cells of normal mucosa at surgical margins correlates with risk of relapse 13,15,16 . An ongoing clinical trial is prospectively evaluating normal mucosa at HNSCC margins for immunohistochemical overexpression of p53 and eIF4E as a proof‐of‐principle for molecular margin evaluation 19 . However, the lack of universal overexpression of p53 in HNSCC may restrict its utility.…”

Role of Immunohistochemical Markers in Surgical Margins of Patients with Head and Neck Carcinoma – A Systematic Review

“…The main characteristics of the eligible studies are summarized in table 1. The total number of patients was 269, three articles were from Asian [1,11,12], and five were from non-Asian ethnicity [8,9,10,13,14]. Four studies composed of OSCC [10,[12][13][14], one study compose of OSCC with Oropharynx SCC [8] and three composed of HNSCC [1,9,11] patients.…”

“…The total number of patients was 269, three articles were from Asian [1,11,12], and five were from non-Asian ethnicity [8,9,10,13,14]. Four studies composed of OSCC [10,[12][13][14], one study compose of OSCC with Oropharynx SCC [8] and three composed of HNSCC [1,9,11] patients. All analyzed histopathologically negative surgical margin specimens and immunohistochemistry was used as detection method.…”

“…Head and neck cancer are the eighth most common cancer worldwide with majority being head and neck squamous cell carcinoma (HNSCC). HNSCC arise in the epithelial linings of the oral cavity, sino-nasal tract, pharynx, larynx and paranasal sinuses [1]. HNSCC is increasing rapidly since past decades and oral squamous cell carcinoma (OSCC) is the commonest tumor of head and neck region [2].…”

Sarcoma Molecular Pathological Diagnosis of FFPE Tissues without Dewaxing based on Lipidomic Profiles using SpiderMass Technology

“…FFPE tissues are, thus, not only useful for high-quality histological imaging, in-situ hybridization (ISH) and immunohistochemistry (IHC), but they also represent a wealth of information for retrospective analyses. However, despite the integration of these multimodal exams, targeting both morphological and cellular tissue features as well as the distribution of speci c mRNA and proteins markers, cancer diagnostics remains labor intense and di cult (1,2). For example, some lesions such as soft tissue sarcomas, which form a highly complex and heterogeneous group of more than 100 known subtypes, are di cult to discriminate because a great number of them present morphological overlaps (3)(4)(5).…”