08-10-2012, 05:29 PM
Malignant laryngeal cancers
INTRODUCTION
In worldwide head and neck cancer is one of the malignant tumors. More than 90 % of head and neck cancers are squamous cell carcinomas (1). Different anatomical locations of head and neck cancers are larynx, hypopharynx , oropharynx and lip/oral cavity (2). Investigations on laryngeal carcinomas (LSCC) indicate that the patients that having lymph node metastasis as well decreases the survival rate up to 50 % (3). The present techniques for example imaging, magnetic resonance, ultrasound and computed tomography can only detect the late metastasis, but microscopic ones cannot be recognized (3). Therefore it is very crucial to utilize markers that studied on biopsy material of primary tumor to predict the metastatic behavior and further to compare between metastatic and non-metastatic patients. Definitely, one single marker is not sufficient and thus a group of them that have a role in this process is required for a precise evaluation and consequently to improve treatment methods.
One of the inhibitor of apoptosis protein (IAP) family members is survivin. Surviving expression can cause apoptosis resistance. Moreover, surviving has a significant role in stimulation of angiogenesis through vascular endothelial growth factor (VEGF), and in regulation of cell proliferation and apoptosis inhibition (4). Survivin is important for its high level of tumor-specific expression; though it cannot be detected or expressed in differentiated at very low levels (4). High surviving expression was identified in various tumors for instance in head and neck, bladder, breast and ovary cancers (5, 6, 7, 8). In previous studies such as Dong et al research high levels of surviving expression was defined in laryngeal squamous cell carcinomas (LSCC) patients, using immunohistochemistry analysis, which significantly correlated with tumor site, tumor size, poor differentiation, lymph node metastasis and advance stage (5). In tumor cells overexpression of survivin cause abnormal cell cycle and may, consequently, allow cells with spindle defects or abnormal chromosome assembly to continue cell division and blocks activation of caspase-9, the requirement of the intrinsic mitochondrial pathway initiation of apoptosis (4).
Epidemiology
Malignant laryngeal cancers are the most common malignancies of head & neck, responsible for approximately 40 % of these cancers & for 2.3 %of all malignant tumors in males & 0.4 % of all malignant tumors in females. (16, 18)
In United States, approximately 11,300 cases of laryngeal cancer were diagnosed & there will be approximately 3660 deaths. The male-to-female ratio is 3.8:1.the higher ratio in males is due to an increased exposure to risk factors rather than inheriting gender tendency, so as number of female smokers has increased over the past 60 years, the ratio has narrowed from over 15:1 to 3.8:1. Over 90 % of cancers occur in people older than 40 years old, & 85 % to 95 % of these are squamous cell carcinoma (SCC). (17)
The estimated survival rate for laryngeal cancer is 67%.This survival rate doesn’t change significantly over 20 years, but it still places laryngeal cancer as one of most curable cancers. (19)
Histologically, the most common form is SCC, compromising for 95 % of laryngeal malignancies with the glottis being the most frequently affected sub site. (19)
Risk factors
The major risk factors for laryngeal cancer are tobacco smoking and alcohol consumption. Tobacco use is a primary factor with dose-dependent relationship. Smoking up to half-a-pack per day has 4.4-fold relative risk, and smoking more than two packs per day has 10.4-fold relative risk. (19). Also smoking cessation slowly decrease risk of laryngeal cancer but it takes more than twenty years returning to its base line. Risk of glottic and subglottic tumor sites increased in both heavy and light smokers, while it increased for supraglottic tumors only in heavy smokers. (20)
Histology, sites of occurrence, and staging
Keratinized or non-keratinized squamous cell carcinomas are great majority of laryngeal cancers, which is classified to squamous cell carcinoma in situ, microinvasive SCC, Or invasive SCC. More aggressive variants of squamous cell carcinoma are rare entities of spindle cell carcinoma basaloid SCC. Verruccous carcinoma is a well-differentiated variant of squamous cell carcinoma that is locally destructive but doesn’t metastasize and will respond to complete surgical excision. Non-squamous cell carcinomas include approximately 1-5 % of carcinomas of larynx. Among these non-squamous tumors, those of salivary, cartilaginous, and neuroendocrine origin are the most common. (19, 21)