The p53 gene is a tumour suppressor gene that encodes a 393-amino-acid nuclear DNA-binding phosphoprotein. The significance of p53 detection is that p53 mutation is linked with chemo-resistance and transformation to more aggressive disease in a large number of tumour types and it was confirmed that mutant p53 is involved in neoplastic transformations. In addition, the expression of p53 has been closely correlated with clinicopathological findings. Since breast cancer has been reported as one of the most frequent malignancies in women in Malaysia, the expression of p53 was studied in 382 cases of invasive ductal carcinoma of the breast, obtained from three major hospitals in the North-East States of Malaysia. The study utilized an enzyme immunohistochemistry assay for the detection of p53. It was found that p53 was expressed in 29.6% of all the study cases. Furthermore, its expression was significantly correlated with the age and the clinical grading of the disease. No significant statistical correlations were depicted with lymph node status, tumour size, side of tumour, and expression of estrogen and progesterone receptors. Nevertheless, knowledge of the p53 status may be valuable in making clinical decisions regarding diagnosis, prognosis and therapy.
Survivin is an inhibitor of apoptosis protein and regulates the cell cycle in the G2/M phase. Survivin is expressed during embryonic and fetal development, selectively over-expressed in common human cancers and completely down-regulated in normal adult tissue. This work was aimed at studying the expression of the survivin homologues and their subcellular distribution in fetal and normal adult tissues of rat. Survivin expression was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded tissue sections of fetal and normal adult tissues of rat using the polyclonal serum SUR12A-CFI. This serum demonstrated intense positive survivin staining in adult kidney, ovary and oviduct, and a variable expression in different fetal organs, with particularly intense expression detected in the adrenal gland, liver, stomach, small intestine, colon, kidney and skin. In both fetal and adult tissues, the expression was predominantly cytoplasmic. It was concluded that survivin was abundantly and prominently expressed during fetal development in rat and that the polyclonal anti-human survivin antibody SUR12A-CFI is reactive with rat survivin.
Autoantibodies to survivin have been reported in lung cancers and in gastrointestinal cancers. A few reports have also described a low prevalence of autoantibodies to survivin and at low titres in the sera of breast cancer patients with no implications for their clinical usefulness. This study was designed to re-examine the prevalence and the clinical correlations of autoantibodies to the tumour protein survivin, in the sera of patients with infiltrating ductal carcinoma of the breast using an ELISA assay. In spite of the low prevalence of autoantibodies to survivin (7%, n = 57), their presence was associated with grade III tumours, with tumour sizes exceeding 10cm, with axillary lymph nodal involvement and with metastases. Moreover, all the autoantibody-positive cases were estrogen and progesterone receptors negative. Furthermore, all the autoantibody-positive cases expressed survivin with high scores.
Survivin is a 16.5-kDa intracellular protein also known as AP14 or BIRC5. It inhibits apoptosis and regulates cell division and belongs to the inhibitors of apoptosis (IAP) gene family. In the majority of neoplasms investigated for survivin expression, high levels of the IAP proteins were predictive of tumour progression, either in terms of disease-free survival or overall survival, thus providing significant prognostic information. Hence, the prognostic value of survivin expression in tumour masses of invasive ductal carcinoma has been investigated. It was found that negative and low expression of survivin correlated significantly with favourable outcomes. Conversely, high expression correlated with unfavourable outcomes. The five-year survival rate was higher among the cases with low and negative survivin expression, compared to those with higher survivin expression. However, this correlation was found to be insignificant statistically. Furthermore, a statistical model has been devised to explain the combined effects of survivin expression and its sub-cellular localisation, p-53 expression and lymph nodal involvement, on the outcomes of these patients.
This work studied the correlations between survivin, bcl-2 and p53 in infiltrating ductal carcinoma of the breast. A total number of 382 cases were collected from 3 hospitals in northeastern Malaysia. Survivin, bcl-2 and p53 were detected by immunohistochemistry on samples prepared from tissue blocks. Significant correlations were found between tumor histological grades and tumor size and lymph node involvement. Highly significant statistical correlations (p<0.001) were found in expression of the markers under study. It is concluded that such significant correlations may imply that the alterations in the expression take place in a concerted fashion, implying that many of these cases may share common abnormalities.
A significant difference in the levels of thyroxine (T4), thyroid stimulating hormone (TSH) and thyroid volume among settlements at various selected Orang Asli locations is reported. The levels improved according to the level of socio-economic development. No significant difference was found in mental performance by location.
In order to study the effect of levothyroxine in the treatment of endemic goitre, a longitudinal study was conducted among the Aborigines in Lanai Post and Sinderut Post, situated in an iodine-deficient area located in the district of Kuala Lipis, Pahang. All subjects in the treatment group (Lanai Post) were given 100 µg of levothyroxine per day and were followed for 1 1/2 years. A total of 311 subjects were examined at baseline, 323 on the first, 256 on the second, 239 on the third and 184 on the fourth visit following levothyroxine supplementation. Goitre prevalence, thyroid hormones, thyroid volume, nutritional status, urinary iodine levels, arterial blood pressure and mental performance were determined. Following the intervention, goitre prevalence was significantly reduced in the treatment group (baseline 42.8% vs final visit 13.0%, p<0.0001); however, no significant difference was noted in the control group. Total T4 levels were increased in the treatment group (p<0.0001), while a significant reduction was noted in the control group (p<0.0001). Thyroid-stimulating hormone levels increased significantly in the treatment group following 1 year of intervention, while no significant changes were observed in the control group. As for the thyroid volume, both groups showed a significant increment following the intervention (p<0.0001). With respect to the nutritional status, the treatment group showed a significant increase in body weight following the intervention (p<0.05). In addition, the mid-arm circumference and body mass index also increased after 1 year of intervention. However, the control group showed a reduction in the waist-hip ratio (p<0.0001). Although there was no statistical difference in the waist-hip ratio in the treatment group, there has been a significant reduction observed after 1 year of intervention. At 1 year, a reduction in skinfold thickness was noted in the treatment group while only the triceps and subscapular were increased in the control group. The body fat was decreased in the treatment group following 1 year of intervention (p<0.0001). No particular trend was noted in the urinary iodine excretion in the treatment group, but surprisingly, the levels were increased in the control group (p<0.0001). A significant increase in both systolic and diastolic blood pressures was observed in the treatment group following 1 year of intervention, but the controls showed a reduction in the systolic blood pressure (p<0.0001). Both groups showed a remarkable increase in mental performance, with a more pronounced effect in the treatment group (p<0.05). The correction of iodine deficiency by levothyroxine supplementation has a short-term beneficial effect in reducing the prevalence of goitre and improving the mental ability among the Aborigines in endemic areas; however, proper monitoring and close supervision are needed to maintain compliance.
INTRODUCTION: Survivin is a 16.5-kDa intracellular protein that inhibits apoptosis and regulates cell division, and belongs to the inhibitors of apoptosis gene family. It appears to have an important role in regulating apoptosis at the cell cycle checkpoints. Survivin has been found to have a differential distribution in cancer compared to normal tissue, as it is over-expressed in malignant tumours.
METHODS: In addition to the demographical analysis of the disease, data from 382 women with invasive ductal carcinoma of the breast were collected from three hospitals in Northeast Malaysia, and analysed for survivin expression by immunohistochemistry.
RESULTS: Invasive ductal carcinoma of the breast was found to be the most prevalent breast cancer type. Survivin was detected in 260 (68.1 percent) study cases. In addition, significant correlations have been shown between survivin expression on one hand, and tumour size and lymph node involvement on the other hand (p-value is less than 0.05). However, no significant correlations were found with other clinicopathological factors, such as tumour histological grade, tumour side, oestrogen and progesterone receptors. Nuclear expression of survivin was detected in 16.5 percent of the study cases, cytoplasmic expression was detected in 24.1 percent, and 27.5 percent of the cases expressed survivin in both nuclear and cytoplasmic locations simultaneously. The subcellular localisation of survivin was significantly correlated (p is less than 0.001) with the lymph node involvement indicating its value in predicting the aggressiveness of tumour cells, since it increases the resistance to apoptosis and promotes cell proliferation.
CONCLUSION: This is the fi rst known report on survivin expression in cancer in West Malaysia and Southeast Asia. It emphasises the importance of the detection of survivin in breast cancer to aid in diagnosis, confirm malignancy, and to assess the disease progress and response to therapy.