A Clinical Study of Hypoxia and Metallothionein Protein Expression in Squamous Cell Carcinomas

• Published in: Clinical cancer research 2000-03, Vol.6 (3), p.855-862
• Main Authors: Raleigh, J A, Chou, S C, Calkins-Adams, D P, Ballenger, C A, Novotny, D B, Varia, M A
• Format: Article
• Language: English
• Subjects: Biomarkers - analysis; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Hypoxia; Female; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Immunohistochemistry; Metallothionein - analysis; Metallothionein - biosynthesis; Neoplasm Staging; Nitroimidazoles - administration & dosage; Nitroimidazoles - metabolism; Proliferating Cell Nuclear Antigen - analysis; Protein Precursors - analysis; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology
• ISSN: 1078-0432; 1557-3265

The objective was to discover whether the oxygen-regulated protein, metallothionein, is expressed in the hypoxic cells of squamous cell carcinomas. Twenty patients with squamous cell carcinoma of the uterine cervix or head and neck were infused with a solution of the hypoxia marker, pimonidazole hydrochloride, at a dose of 0.5 g/m 2 . The following day, biopsies were collected, formalin fixed, paraffin embedded, and sectioned at 4 μm. Sections from each biopsy were immunostained for pimonidazole binding, metallothioneins I and II, involucrin, and proliferating cell nuclear antigen. A total of 84 biopsies were analyzed. Sixty-four of 84 biopsy sections contained hypoxia. Of the hypoxia-containing sections, 43 of 64 or 67% showed no microregional overlap between hypoxia and metallothionein; 7 of 64 showed overlap; and 14 of 64 showed a combination of overlap and no overlap. On a tumor-by-tumor basis, 5 of 7 head and neck and 7 of 13 cervix tumors showed no overlap between metallothionein and hypoxia at the microregional level. Ranges for the percentage of the area of hypoxia in head and neck (