Introduction Head and neck squamous cell carcinoma (HNSCC) constitutes up to 90% of cases among all cancers affecting the head and neck region. 1 It is the 6th leading cancer in the world with overall high global incidence and mortality causing over 550,000 new cases and around 300,000 deaths each year. 2 In Pakistan, collective data report of cancer registry 1994-2013 by Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) has ranked HNSCC to be the third most common tumour in all age groups and the second most common in adults affecting both genders equally. 3 Also, four years (2004- 2008) of aggregated data from five leading cancer hospitals of Pakistan has revealed HNSCC to be the second most common cancer, accounting for 9.9% of all cases. 4 The overall high incidence and mortality rate can be attributed to incomplete understanding of molecular pathways and lack of reliable and validated biomarkers that predict the early diagnosis and prognosis of this alarming disease. Though molecular characterisation of this disease has facilitated the understanding of the molecular mechanisms contributing to the development of HNSCC and recognition of different molecular biomarkers, like p53, hypoxia-induced factors, interleukins (ILs), melanoma-associated antigen (MAGE), microsatellite instability (MSI), matrix metalloproteinases (MMPs), among others, but there are issues of specificity, sensitivity and clinical validation with some of these biomarkers. 5 Therefore, extrication of cellular pathways involved pathogenesis of HNSCC and searching of new diagnostic and prognostic biomarkers is still the need of the hour. 6 Mucins are glycosylated proteins expressed by various epithelial structures and involved in distinct functions, such as cell differentiation, cell adhesion and cell signalling. Changes in their glycosylation pattern are associated with development and progression of malignant diseases and therefore, mucins are analysed as potential markers for diagnosis and progression of epithelial malignancies. 7 Mucin 4 (MUC4), a trans- membrane mucin, has recently appeared as a useful biomarker. It plays its role in tumour progression indirectly through anti-adhesion mechanism or directly through ErbB2 (Receptor Tyrosine Kinase 2) signalling pathway. 8 Variation in its expression and glycosylation has been reported in various epithelial malignancies, like breast, lung, pancreas, oesophagus and cervix. 9 MUC4 is also localised in head and neck squamous J Pak Med Assoc 2178 RESEARCH ARTICLE Immunohistochemical expression of MUC4 in different grades of head and neck squamous cell carcinoma Naila Umer, 1 Nadia Naseem, 2 Saima Chaudhry 3 Abstract Objective: To determine immunohistochemical expression of Mucin 4 in head and neck squamous cell carcinoma and its different histological grades among patients reporting to various tertiary care hospitals in an urban setting. Method: The descriptive study was conducted at the Department of Oral Pathology / Morbid Anatomy and Histopathology, University of Health Sciences, Lahore, Pakistan, from January to July 2017 and comprised cases of head and neck squamous cell carcinoma. Histological diagnosis and grading was done for each case. Haematoxylin and eosin stain followed by immunohistochemistry was done. Relation of Mucin 4 expression with tumour types was explored. SPSS 20 was used for statistical analysis. Result: Of the 63 samples, 40(63.5%) were from male patients. The overall mean age of the patients was 53±3.77 years. Mucin 4 expression was positive in 47(74.6%) cases. Of them, 16(34%) had grade 1 tumour, 28(59.6%) had grade 2 and 3(6.4%) had grade 3 tumour. There was a significant relation (p=0.03) between tumour grades and intensity of Mucin 4 expression. Conclusion: Upregulation of Mucin 4 in tumour tissue with no expression in normal epithelium was found and loss of Mucin 4 expression with increase in tumour grade was noted. Keywords: Mucin 4, MUC4, Squamous cell carcinoma of head and neck, HNSCC, Immunohistochemistry. (JPMA 70: 2178; 2020) DOI: https://doi.org/10.47391/JPMA.217 1,3 Department of Oral Pathology, 2 Department of Morbid Anatomy & Histopathology, University of Health Sciences, Lahore, Pakistan. Correspondence: Saima Chaudhry. Email: saimachaudhry@uhs.edu.pk