Prognostic significance of nuclear and cytoplasmic expression of metallothioneins as related to proliferative activity in squamous cell carcinomas of oral cavity
Jolanta Szelachowska1, Piotr Dziegiel2, Joanna Jelen-Krzeszewska3, Michal Jelen4, Radoslaw Tarkowski1, Iwona Wlodarska1, Barbara Spytkowska5, Iwona Gisterek1, Rafal Matkowski1 and Jan Kornafel1
Departments of 1Oncology, 2Histology and Embryology, 3Maxillofacial Surgery, 4Pathology, Wroclaw Medical University, and 5Department of Radiotherapy, Lower Silesian Oncology Center, Wroclaw, Poland.
Offprint requests to: Piotr Dziegiel, MD, PhD, Department of Histology and Embryology, Wroclaw Medical University, Chalubinskiego 6a, 50-368 Wroclaw, Poland. e-mail: piotr@hist.am.wroc.pl
Summary. Metallothioneins (MT) are low molecular weight proteins with high metal and cystein contents. This study was designed to test the hypothesis that cytoplasmic and nuclear MT expression are of prognostic importance in patients with squamous cell carcinomas of the oral cavity, treated by surgery with subsequent radiotherapy. The second aim of the study was to test the potential correlation between the nuclear and cytoplasmic MT expressions as compared to expression of proliferation markers and other clinicopathological variables. Material and Methods: The studies were performed on tumor samples from 50 patients with diagnosis of squamous cell carcinoma of the oral cavity floor or of oral part of the tongue. All the patients were subjected to radical surgery, accompanied by removal of lymph nodes and post-operative radiotherapy. Results: No significant correlation could be detected between percentage and intensity of MT expression on one hand and proportions of cells with Mcm-2 (minichromosome maintenance protein 2), Ki-67 expressions, nor the grade of malignancy (G) on the other. A significantly shorter survival was detected among patients with tumors of MT expression rated 9 or 12 according to the Remmele scale and among patients with a high percentage (> 50%) of nuclear MT staining. In mulivariate analyses, only OTT (Overall Treatment Time), lymph node involvement and high expression of Mcm-2 were found to be independent risk factors for decreased patient’s survival. Conclusion: This is relevant evidence that MT overexpression could be related to worse prognosis in patients with oral cancer. We have found no relationship between MT expression and proliferative activity. Histol Histopathol 23, 843-851 (2008)
Key words: Oral cancer, Squamous cell carcinoma, MT, Mcm-2, Ki-67