We report a case of a 48-year-old Indian male who presented with swelling and firmness in his left upper part of the abdomen of one month duration with anorexia and weight loss. Initial examination revealed an intra abdominal mass of around 16.8x11.0x24.5cm with minimal left sided pleural effusion. A biopsy from the mass confirmed the diagnosis of gastrointestinal stromal tumour (GISTs) as supported by immmunohistochemistry results which showed strong positivity for c-kit while stains for smooth muscle actin, desmin, myoglobin, S100 Protein and cytokerstin remained negative. The patient was not suitable for surgical intervention in view of advanced tumor, and Imatinib Mesylate 400mg daily was started with the aim of making the tumor operable. Such therapy lasted for twenty months and was tolerated well by the patient. It then resulted in gradual tumor regression, following which the patient underwent successful tumor resection. Post surgical resection patient had no radiological evidence of intra abdominal tumor but mild left sided pleural effusion with left lower lobe atelectasis. The patient had uneventful post operative recovery and he is currently on Imatinib mesylate and tolerating treatment well with mild skin rash. The experience with preoperative imatinib on surgical resection rates and post operative outcomes is limited especially with primary locally advanced GISTs. In our case successful surgical resection was possible for a huge locally advanced GIST with unusually prolonged treatment of twenty months with imatinib preoperatively.
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.
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.