Cyclin D1 overexpression in primary hypopharyngeal carcinomas

• Published in: Cancer 1996-08, Vol.78 (3), p.390-395
• Main Authors: Masuda, Muneyuki, Hirakawa, Naoya, Nakashima, Torahiko, Kuratomi, Yuichiro, Komiyama, Sohtaro
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Neoplasm - analysis; Biological and medical sciences; Biomarkers, Tumor - analysis; Carcinoma, Squamous Cell - chemistry; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; cervical lymph node metastases; Cyclin D1; Cyclins - analysis; Female; Humans; Hypopharyngeal Neoplasms - chemistry; Hypopharyngeal Neoplasms - mortality; Hypopharyngeal Neoplasms - pathology; Immunohistochemistry; Ki-67 Antigen; Lymphatic Metastasis; Male; Medical sciences; MIB‐1; Middle Aged; multimodality treatment; Neoplasm Proteins - analysis; Nuclear Proteins - analysis; Oncogene Proteins - analysis; Otorhinolaryngology. Stomatology; Prognosis; prognostic factor; Survival Rate; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/(SICI)1097-0142(19960801)78:3<390::AID-CNCR2>3.0.CO;2-O

BACKGROUND Hypopharyngeal squamous cell carcinomas (HPCS) are associated with an extremely poor prognosis. Generally, conventional clinicopathologic factors have only limited value as prognostic factors for this malignancy. It is therefore clinically important to identify new prognostic factors that accurately reflect the biologic aggressiveness of this malignancy. The amplification and overexpression of the cyclin D1 protooncogene have been reported in a variety of malignancies, and are thought to be related to tumor progression. Based on this phenomenon, the authors immunohistochemically evaluated overexpression of the cyclin D1 gene in 42 cases of primary HPCS. In addition, the immunohistochemical staining of the proliferation marker MIB‐1 (Ki‐67 antibody) was also performed. METHODS Formalin fixed, paraffin embedded biopsy specimens obtained prior to treatment were examined. Cyclin D1 and Ki‐67 were detected using monoclonal antibodies by means of the streptavidin‐biotin method. The relationship between cyclin D1 overexpression and the stage, histologic grade, presence of lymph node metastases, proliferation index, and survival was then statistically analyzed. The correlation between the proliferation index, other clinicopathologic factors, and survival was also evaluated. RESULTS Twenty‐three (54.8%) HPCS specimens showed a 20% or greater immunoreactivity for cyclin D1. Cyclin D1 overexpression was related to cervical lymph node metastases (P = 0.037) but not to clinical stage, histologic grade, or the proliferation index. Cyclin D1 negative tumors were associated with a significantly better prognosis (P = 0.023), particularly in patients who underwent multimodality treatment. Finally, the MIB‐1 labeling index showed no correlation with either the clinicopathologic parameters or overall survival. CONCLUSIONS Based on these findings, cyclin D1 immunohistochemical staining is considered to be useful, not only as a prognostic factor for HPCS, but also as a means of determining the optimum treatment for each individual patient. Conversely, the MIB‐1 labeling index appears to have no clinical significance in HPCS. Cancer 1996;78:390‐5.