ABSTRACT
BACKGROUND: There is a statistically significant association between human leukocyte antigen (HLA) Class I antigen expression and improved prognosis for some patients. This association reflects the control of tumor growth by HLA Class I antigen-restricted, tumor-associated antigen-specific cytolytic T cells. However, progression of other malignant diseases is not associated with the loss of HLA expression. These observations show that the poor prognosis of a subset of tumors, despite high HLA Class I antigen expression, may reflect the development of alternative mechanisms utilized by tumor cells to escape from immune recognition and destruction. METHODS: The authors evaluated the possible correlation between the expression of the antiapoptosis gene, Survivin, HLA Class I, and progression of tonsillar squamous cell carcinomas (TSCC) lesions. Tissue microarrays were constructed from primary TSCC, metastatically involved lymph nodes, adjacent normal mucosa, and tonsillar parenchyma excised for nonmalignant conditions. RESULTS: Immunoperoxidase staining of tissue sections demonstrated that Survivin expression is significantly higher (P < 0.001) in malignant tumors than in normal tissue samples. In addition, Survivin expression is significantly higher (P = 0.05) in metastatic than in primary lesions. Survivin expression in primary lesions correlated positively with delta (P = 0.025), tapasin (P = 0.028), and HLA Class I antigen (P = 0.006) expression. The expression patterns of delta, tapasin, HLA Class I antigen, beta-2-microglobulin, and Survivin did not demonstrate any significant association with the clinical course of disease. CONCLUSIONS: For TSCC that maintain the expression of HLA Class I antigen, overexpression of Survivin may provide an alternative explanation for tumor progression.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Histocompatibility Antigens Class I/metabolism , Microtubule-Associated Proteins/metabolism , Tonsillar Neoplasms/metabolism , Antigen Presentation/physiology , Antiporters/metabolism , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/therapy , Case-Control Studies , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/metabolism , Humans , Immunoenzyme Techniques , Immunoglobulins/metabolism , Inhibitor of Apoptosis Proteins , Intracellular Signaling Peptides and Proteins , Male , Membrane Proteins/metabolism , Membrane Transport Proteins , Middle Aged , Neoplasm Proteins , Neoplasm Staging , Survivin , Tonsillar Neoplasms/pathology , Tonsillar Neoplasms/therapy , beta 2-Microglobulin/metabolismABSTRACT
Despite advances in diagnosis and treatment, the prognosis for patients with stage III-IV laryngeal cancer is not significantly different than it was four decades ago [1]. This failure to improve survival is multifactorial and is likely linked to controversy surrounding optimal treatment regimens for a heterogeneous patient and tumor population. At the root of this controversy is a lack of randomized controlled trials that compare different therapeutic options, personal and institutional treatment philosophies, and a paucity of standardized functional and quality-of-life outcome measures for specific treatment modalities. Therapeutic decision making is further complicated by the potential use of organ preservation approaches in some patients [2**, 3*, 4**]. Clearly, quality-of-life considerations are an integral part of treatment planning and a well-informed patient is necessary to achieve an optimal result. Philosophically, it is the physician's responsibility to recommend the best treatment option and to explain the other viable treatment strategies. It is our opinion that conservation laryngeal surgery represents the mainstay of treatment for patients with advanced laryngeal carcinomas, whose tumors have characteristics amenable to these approaches and who functionally can tolerate such procedures. For those patients who would likely require a total laryngectomy or who are not suitable for surgical conservation, organ preservation should be used as a primary option in a controlled setting.
