Case Report: Madam Tan, a 71-year-old Malaysian Chinese lady, otherwise healthy, presented to her local GP with a complaint of a nodule over the left cheek that had been there for more than a decade. Her concern was that the lesion was growing and had become conspicuous. She had spent most of her life as a farmer working in her orchard.Upon examination, she had an obvious dome-shaped nodule over the left cheek measuring approximately 1.8 cm in diameter. The lesion was firm, pigmented, well-demarcated, and slightly ulcerated at the top. Clinically, she was diagnosed with a pigmented nodular basal cell carcinoma of the left cheek. Examination of the systems was unremarkable.She requested that the consulting GP remove the growth. The cost for specialist treatment and waiting time at the local hospital were her concerns.
Clinical Questions: Can the basal cell skin cancer be excised safely and effectively in the local primary care setting? What are the crucial preoperative concerns?
METHODS: Surgical samples from seven patients with a total of 17 sequential biopsies were retrieved for the study of p53 gene expression using immunohistochemical stain, and gene status by PCR-SSCP for exons 5-8. The tumours were graded according to the WHO classification criteria. P53 was distinctly over-expressed in five transformed higher grade biopsies, and all except one showed electrophoretic mobility shift in PCR-SSCP analysis. Sequencing analysis revealed single nucleotide substitutions in three of four of these high-grade transformed cases with band shift (75%), whereas some other studies reported a lower frequency of 25-30%, and mobility shift result was found to correlate with P53 expression. Lower grade tumours without P53 over-expression did not demonstrate band shift, and sequencing analysis did not reveal mutations.
CONCLUSIONS: We demonstrated the feasibility of adopting PCR-SSCP for screening of p53 mutations in archival tissue samples in this study, and there is a strong correlation of p53 gene over-expression and mutation events in high-grade transformed tumours.
METHODS: Diurnal variation of intraocular pressure was measured in 202 eyes of suspected open-angle glaucoma patients and 100 control eyes, at 4-hourly intervals for 24 hours (phasing). Based on the phasing results, optic disc changes and visual field defects, the patients were diagnosed as primary open angle glaucoma (POAG), normal tension glaucoma (NTG), ocular hypertension (OHT), or physiologic cup (PC), or still remained as glaucoma suspects due to inconclusive diagnosis. The last group (glaucoma suspects) was then followed up 6-monthly for their eventual outcome.
RESULTS: The highest percentage of suspected glaucoma patients had peak (maximum) readings in the mid-morning (10-11 A.M.) and trough (minimum) readings after midnight (2-3 A.M.); the highest percentage of control group had peak readings in the late evening (6-7 P.M.) and trough readings after midnight (2-3 A.M.). The mean amplitude of variance was 6 mm Hg in suspected glaucoma group and 4 mm Hg in the control group. After 'phasing', 18.8% of the suspected glaucoma patients were diagnosed as POAG, 16.8% as NTG, 5% as OHT, and 28.7% as physiologic cup; 30.9% remained as glaucoma suspects. After 4 years follow-up, 70% of the glaucoma suspects still remained as glaucoma suspects, 6.7% developed NTG and another 6.7% POAG; 16.6% were normal.
CONCLUSIONS: Serial measurement of IOP ( phasing) in a 24-hour period is still needed, in order not to miss the peak and the trough IOP readings in suspected open-angle glaucoma patients, which helps in better management of glaucoma. Among 30.9% of patients who remained as glaucoma suspects after the initial phasing, 13.4% developed NTG/POAG over a period of 4 years.