Immunohistochemical Expression of Excision Repair Cross Complementation Group 1 (ERCC1) in Laryngeal Squamous Cell Carcinoma and Its Correlation With Response to Radiotherapy.

Overview

1. Determine the correlation between immunohistochemical expression of ERCC1 in laryngeal cancer cells with clinico-pathological variables. 2. Assess the correlation between ERCC1 expression and response to radiotherapy.

The global burden of laryngeal cancer increased during the past 3 decades. A total number of 210,606 new cases of laryngeal cancer have been diagnosed in 2017 (2.76 new cases per 100,000 inhabitants) worldwide, with a prevalence of 1.09 million cases (14.33 cases per 100,000 inhabitants), accounting for as many as 126,471 deaths (1.66 per 100,000 inhabitants). The incidence and prevalence have both increased by 12.0% and 23.8%, respectively during the past 3 decades, whilst mortality has declined by approximately 5 %. In Egypt, laryngeal cancer represents 5.7% of all body malignancies and 38.7% of the head and neck malignancies. Squamous cell carcinoma is the most common histologic variant and accounts for 85-95% of all malignant tumors of the larynx. According to World Health Organization it is the second most common malignancy of the upper aerodigestive tract. It occurs more in people above 40 years of age and more common in males. The larger number of laryngeal cancer cases originate from the glottic region (i.e., approximately two-third), followed by the supraglottic area (about 30%), whilst trans-glottic and purely subglottic tumors are generally less frequent. Excision repair cross-complementation group 1 (ERCC1) is a key DNA repair gene in the nucleotide excision repair pathway which is activated in the repair of intra- and interstrand DNA crosslink. Ionizing radiation (IR) acts directly or indirectly to cause various forms of deoxyribonucleic acid (DNA) damage in cells. DNA damage repair is initiated after the cell is genetically damaged. Nucleotide-excision repair (NER) is one of the ways of DNA repair. ERCC1 is a structure-specific endonuclease that cut DNA at single-stranded/double-stranded junctions with a specific polarity. There is some clinical evidence suggesting that ERCC1 status (ERCC1 mRNA expression, ERCC1 protein expression, and ERCC1 polymorphisms) is associated with platinum-based therapy efficacy in some kinds of cancers. In a previous meta-analysis, ERCC1 protein low expression status detected by immunohistochemical methods significantly correlated with higher response to platinum-based chemotherapy in ovarian cancers. Another meta-analysis evaluated non-small cell lung cancer patients treated with platinum-based chemoradiation showed that both low tumoral mRNA and protein levels were associated with a better response rate and overall patient survival. In head and neck squamous cell carcinomas, the available studies have a conflict in results. Of six studies evaluating the relation between ERCC1 status and outcomes of head and neck cancer patients, three showed positive and another three were with negative results.

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