Collagen Markers in Hypopharyngeal Cancer. A retrospective study.
Research type
Research Study
Full title
Do SMA positive myofibroblasts exist in the tumour stroma of hypopharyngeal cancer and does presence correlate to survival? A retrospective study.
IRAS ID
215502
Contact name
M King
Contact email
Sponsor organisation
Poole Hospital Foundation Trust
Duration of Study in the UK
0 years, 8 months, 28 days
Research summary
Head and neck cancer is the 6th commonest cancer worldwide accounting for over 580,000 new cases and 297,000 deaths annually. It is made up of a heterogeneous mix of anatomical subsites within the head and neck, and the vast majority are squamous cell carcinomas. The hypopharyngeal subsite extends from the oropharynx cranially to the oesophagus caudally.
Hypopharyngeal cancer, although relatively rare (approximately 5% of all upper aerodigestive tract cancers are of this subset), is an aggressive malignancy. Despite advances in surgical technique, radiotherapy approaches and chemotherapeutic regimens, patients with hypopharyngeal cancer still have the worst survival of any head and neck cancer (30% at 5 years) and there is little understanding as to why this is the case. The tumours are often advanced at presentation, frequently demonstrating multifocal lesions and early submucosal extension. Lymphatic metastasis in the neck is commonly evident at the time of diagnosis.
Beyond publication of personal or single institution series, there is little information in the literature concerning hypopharyngeal cancer, its nature or its outcomes. Two current basic science studies exist to demonstrate the presence of oncogenic markers of hypopharyngeal in vitro. No basic science-clinical studies exist. There is no comparable data series beyond numbers totalling 30 and often hypopharyngeal cancer is often interpreted in conjunction with other head and neck cancers. There is a real need for a large definitive series of hypopharyngeal carcinoma, to not only fulfil understanding of the presentation, diagnosis and management of the disease, but also to accurately detail its outcomes and parameters that might effect said outcome.
Fibroblasts play an important role in the pathogenesis of solid body tumours. In normal physiology, fibroblasts contribute significantly to tissue homeostasis by regulating the extracellular matrix, by synthesising collagen and other proteins. In recent years, it has become apparent that the process of carcinogenesis involves manipulation of the local tumour microenvironment by the dividing cancer cells. One of the most abundant cells in the stroma of a solid bodied tumour are fibroblasts.
Cancer cells exert an ability to activate and sustain activation of fibroblasts, which subsequently allow tumour cells to multiply, metastasise and evade cancer therapies. These so called Cancer-associated fibroblasts (CAFs) reside within the tumour microenvironment and may promote the malignant transformation process by encouraging angiogenesis, lymphangiogenesis, production of chemokines and cytokines. CAF may be distinguished from normal fibroblasts by the expression of α-Smooth Muscle Actin (α-SMA). These are cytoskeletal proteins responsible for cell motility and invasion, which are important components of epithelial tumourigenesis. Similar studies have demonstrated the pathogenicity of CAFs in Oral Cavity, Ovary, Colorectal and Oesophageal cancer.
This study will collect patient outcome information and matched biopsy tissues (from archived routine biopsies - no study specific procedures are required). Formalin-fixed and paraffin-embedded hypopharyngeal tissue will be used to create a tissue microarray (TMA), to examine the extent of CAF infiltration (by assessment of collagen markers (tissue components activated inappropriately by tumour) such as α-SMA expression, along with other immune cells e.g. CD8+, CD4+, CD19+, FoxP3+ and CD25) via RNA isolation and immunocytochemical staining. The expression of these markers will then be analysed with patient outcome data.
We expect to create the largest database of its kind, spanning three countries and six sites; Liverpool, Poole, Portsmouth, Sardinia, Southampton and Toronto.
Approval has already been attained from the relevant heads of department at each site.REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
16/EM/0497
Date of REC Opinion
8 Dec 2016
REC opinion
Favourable Opinion