Elevated frequency of p53 genetic mutations and AgNOR values in squamous cell carcinoma.

BACKGROUND: Epidermal squamous cell carcinoma (SCC) isa common malignancy in Pakistan. We hypothesize that it is characterized by higher frequency of p53 genetic mutations and increased AgNOR values compared with squamous cell papilloma(SCP) and basal cell carcinoma (BCC). EXPERIMENTAL DESIGN: To test our hypothesis, 140 skin biopsies(including 20 normal skin, 20 SCP, 20 BCC and 80 SCC samples of various grades) were examined for p53 mutations using immunohistochemistry (IHC) and polymerase chain reaction (PCR). AgNOR staining was used for histological determination of AgNORindex. RESULTS: Both markers were undetectable in normal skin and were low in SCP. They were upregulated in BCC and SCC. PCR experiments revealed p53 mutations in 70% and 96.25% of BCC and SCC, respectively. Higher AgNOR values were seen in SCC than in BCC (mean AgNOR count = 5.81 +/- 31 and 8.36 +/- 19; percentage of AgNOR was 43.5% and 53% in BCC and SCC, respectively). Finally, p53 IHC score was found to be related to the AgNOR index in the histological grading of BCC and SCC (r = 10.983, p < 0.0001). CONCLUSION: Our results suggest that a higher frequency of p53 genetic mutations and increased AgNOR values exist in SCC compared with BCC and SCP. 'Consequently, SCC patients may have poorer prognosis'.

An updated audit of fine needle aspiration cytology procedure of solitary thyroid nodule.

This study was conducted to see the sensitivity, specificity, and accuracy of fine needle aspiration cytology (FNAC) for solitary thyroid nodules and to compare our experience with that of other regions of the world. It was a prospective cross sectional study conducted on 76 thyroid samples submitted and reported at the Department of Pathology, King Edward Medical University, Lahore. There were 65 (85.5%) females and 11 (14.5%) males. Male to female ratio was 1:5.9. Ages of the patients ranged from 10 to 60 year with mean age 35.37 +/- 12.17. Thirty-three (43.42%) samples were indeterminate. There were 30 cases (39.47%) of benign lesions, comprising of colloid goiter, follicular adenoma, and diffuse hyperplasia. The final reports of these cases were almost the same. On FNAC, 13 cases were declared as malignant (6 cases) or suggestive of malignancy (3 cases) or suspicious for malignancy [4 cases (5.26%)]. Only 9 cases (11.84%) were clearly committed as malignant lesions, comprising of papillary carcinoma, anaplastic carcinoma and suggestive of follicular carcinoma. Comparison of malignant cases on histopathology (14 cases) was close to that of FNAC (13 cases). After comparison of FNAC results with histopathology, overall sensitivity of FNAC was found to be 90%, specificity 87.5%, and accuracy 87%, while positive predictive value (PPV) was 93% and negative predictive value (NPV) was 79.5%. In conclusion, we recommend this procedure in the light of views of other experts as a primary investigation of thyroid lesions. We strongly recommend the suggestion that in a patient with one or more thyroid nodule, FNAC should be advised for every patient for exclusion of cancer. We will also encourage the clinicians to embrace this procedure in the initial management of patients. As FNAC is inexpensive, sensitive, specific, and an accurate procedure it should be adapted as an initial investigation of thyroid diseases in all tertiary hospitals in developing countries like Pakistan.

Chemotherapeutic/chemopreventive role of retinoids in chemically induced skin carcinogenesis in albino mice.

OBJECTIVE: To determine the chemotherapeutic effect of retinoids on albino mouse skin. METHODS: Eighty albino mice were selected for this study and were divided into four groups (A-D, 20 mice in each group). 7,12-Dimethylbenz(a)anthracene (DMBA) and tetradecanoylphorbal-13-acetate (TPA) were given for 15 weeks to produce tumors. Retinoids were given topically and orally after the development of tumors for the following 15 weeks. RESULTS: Of the 80 mice, 69 (86.25%) developed different types of lesion and 11 (13.75%) remained lesion free. Of the 69 mice that developed lesions, 50 (62.50%) developed benign lesions and 19 (23.75%) developed malignant lesions. In all groups of mice, treatment with retinoids was effective against all benign lesions and the early stages of carcinogenesis of the skin. The chemotherapeutic effect against malignant tumors was not satisfactory. CONCLUSION: This study demonstrates that retinoids are effective as chemopreventive agents in premalignant lesions of the skin, but have a very weak chemotherapeutic role in malignant neoplasms. If retinoids are given at an early stage, they can cause regression of premalignant lesions of the skin. They are best administered both orally and parenterally. These agents should be recommended as they reduce the potential effects of carcinogenesis.

Modified method of AgNOR staining for tissue and interpretation in histopathology.

This study was conducted in the department of Pathology King Edward Medical University, from June to December 2002 to introduce the new method of AgNOR staining and its interpretation to increase its reliability. A total of 60 brain specimens were stained with modified AgNOR technique. The diagnosis of malignancy was made on H & E staining. AgNOR counts, variation in size and dispersion of AgNOR dots in cells were graded and compared in malignant and non-malignant lesions. Modified method of AgNOR staining and interpretation was an easy, reliable and reproducible alternative to traditional AgNOR techniques for evaluating proliferation activity of cells in malignant and benign brain lesions. mAgNOR counts of different grades of astrocytoma (2.97+/-0.96, 3.97+/-0.43, 6.01+/-2.74 and 8.01+/-3.56) were significantly (P<0.01) greater when compared with counts of normal brain (0.40+/-0.01), and reactive gliosis (0.60+/-0.01). AgNOR size and dispersion were of higher grade in a significantly greater proportion of malignancy when compared with benign conditions (P<0.05). The AgNOR dots were brighter and more clear with modified staining when compared with previous studies. We conclude that modified AgNOR staining technique is simple, quick and reliable to evaluate cell proliferation by detecting AgNORs size and dispersion. In future, AgNOR size and dispersion should be considered rather than the count only. We recommend the use of morphometry for AgNOR size in future. We also recommend the use of modified AgNOR staining for obtaining sound and confidant results in routine paraffin sections.