Morphological alterations and the effect on tumour supressor gene expression induced by high dose rate intraluminal brachytherapy in oesophageal carcinoma

• Main Author: Sur, Monalisa
• Format: Others
• Language: en
• Published: 2014
• Online Access: http://hdl.handle.net10539/14479

1. To review the radiation changes in total oesophagectomy specimens from 10 patients with Squamous cell carcinoma [SCC], given preoperative High Dose Rate Intraluminal Brachytherapy [HDRILBT] of 20 Gy in two fractions of 10 Gy each weekly. 2. To evaluate the effect of HDR ILBT on p-glycoprotein, the MDR-1 gene product in oesophageal SCC. 3. To examine the effect of HDR ILBT in the expression of p53, bcl-2 and apoptosis in oesophageal cancer. METHODS Ten consecutive patients with a preoperative diagnosis of moderate to poorly differentiated SCC of the oesophagus were investigated in this study. 1. The post-brachytherapy oesophagectomy specimens were sampled at the resection margins, edge of irradiated length, 1 cm from edge of visible tumour proximally and distally, centre of the tumour and lymph nodes. Both pre and post HDR ILBT specimens were: 2. examined for the expression of p-glycoprotein, the MDR-1 gene product using antibody to p-glycoprotein (clone JSB-1, using the modified sandwich technique). 3. examined for the expression of p53, bcl-2 and apoptosis using immunohistochemical markers. RESULTS 1. Radiation changes in the form of fibrosis was limited to the submucosa at the resection margins, circular muscle layer at the edge of irradiated length and full thickness at 1 cm from the edge of visible tumour and centre of the tumour. Surface epithelium did not show any changes at the resection margins but showed basal cell hyperplasia at the edge of the irradiated length, and ulceration at 1 cm from the edge of visible tumour and centre of the tumour. Endarteritis obliterans in the blood vessels were seen only 1 cm from the edge of visible tumour and at the centre of tumour. Necrosis, intense keratin formation and giant cell reaction were observed at the centre of the tumour. When compared to the pre-radiotherapy biopsies, the amount of keratin in the post-radiotherapy specimens was extensive. 2. p-glycoprotein was not expressed in either the pre-brachytherapy or postbrachytherapy tumour tissue specimens. 3. In one patient there was no expression of p53 in either pre or post-brachytherapy specimens. In 8 patients, p53 staining was strongly positive (3+), with approximately 50% or more cells showing a diffuse pattern in the pre-brachytherapy biopsies. The tumour areas of the postbrachytherapy specimens of these patients showed strong 3+ positivity with p53 (10-50% positive cell count), with the pattern being focal and peripheral in the tumour islands. The centre of the tumour islands showed necrosis and/or keratinization. In one patient, the prebrachytherapy biopsy showed expression of p53, whilst the post-brachytherapy specimen was negative, bcl-2 expression was equivocal in both pre and post-brachytherapy. Apoptosis was not demonstrated in either the pre or post-brachytherapy tissue sections in the presence of positive control. CONCLUSION 1. HDRILBT may induce keratin gene in the irradiated cells to differentiate towards better differentiated cells. Preopa?,tive HDR ILBT may have a role in improving the prognosis of early oe sophageal cancer treated with a combination of radiotherapy and surgery. 2. p-glycoprotein expression is of no value in predicting the responsiveness of the tumour to radiotherapy in SCC of the oesophagus. 3. Brachytherapy does not cause cell death by apoptosis but by necrosis and maturation of the cells into better differentiated cells which is caused by OH" free radical and induction of the keratin gene respectively. It is possible that brachytherapy may cause destruction of cells producing wild type p53, while mutant p53 in cells located at the tumour periphery escapes the effect of brachytherapy. This maybe responsible for the high incidence of local recurrence and distant metastasis in oesophageal cancer treated with radiotherapy. Brachytherapy does not affect bcl-2 expression in oesophageal cancer.