PURPOSE: To examine whether p53 tumour suppressor gene alterations can be used to predict tumour response to pre-operative chemo-radiation in locally advanced rectal cancer in terms of reduction in tumour size and local failure. METHODS: p53 alterations were studied in pre-treatment biopsy specimens of rectal carcinomas from 48 patients by immunohistochemistry (IHC) and polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) gene mutation analysis. Pre-operative pelvic radiotherapy was delivered with four fields, 45 Gy to the ICRU point in 25 fractions over 5 weeks. A radio-sensitising dose of 5-fluorouracil (500 mg/m(2)) was delivered concurrently for 6 days of the 5-week schedule (days 1, 2, 3 and days 22, 23 and 24). Total meso-rectal excision was planned 4 to 6 weeks from completion of pre-operative treatment. Response to therapy was assessed by macroscopic measurement of the surgical specimen by a pathologist who was unaware of the pre-treatment tumour size or of the p53 status. RESULTS: IHC evidence of p53 protein accumulation was found in 40% of tumours, p53 gene mutation in 35% and p53 alteration (either or both changes) in 46%. The average reduction in tumour size was 53% in the group with 'wild-type' p53 (IHC-/SSCP-) and 63% in the group with altered p53 (either IHC+ or SSCP+; P=0.18). No significant differences in tumour size reduction or local failure were observed in the groups with p53 overexpression or p53 mutation compared with normal. CONCLUSIONS: p53 alteration detected by IHC or SSCP analysis is not a clinically useful predictor of local response to pre-operative adjuvant therapy in advanced rectal carcinoma.
PURPOSE: To examine whether p53tumour suppressor gene alterations can be used to predict tumour response to pre-operative chemo-radiation in locally advanced rectal cancer in terms of reduction in tumour size and local failure. METHODS:p53 alterations were studied in pre-treatment biopsy specimens of rectal carcinomas from 48 patients by immunohistochemistry (IHC) and polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) gene mutation analysis. Pre-operative pelvic radiotherapy was delivered with four fields, 45 Gy to the ICRU point in 25 fractions over 5 weeks. A radio-sensitising dose of 5-fluorouracil (500 mg/m(2)) was delivered concurrently for 6 days of the 5-week schedule (days 1, 2, 3 and days 22, 23 and 24). Total meso-rectal excision was planned 4 to 6 weeks from completion of pre-operative treatment. Response to therapy was assessed by macroscopic measurement of the surgical specimen by a pathologist who was unaware of the pre-treatment tumour size or of the p53 status. RESULTS: IHC evidence of p53 protein accumulation was found in 40% of tumours, p53 gene mutation in 35% and p53 alteration (either or both changes) in 46%. The average reduction in tumour size was 53% in the group with 'wild-type' p53 (IHC-/SSCP-) and 63% in the group with altered p53 (either IHC+ or SSCP+; P=0.18). No significant differences in tumour size reduction or local failure were observed in the groups with p53 overexpression or p53 mutation compared with normal. CONCLUSIONS:p53 alteration detected by IHC or SSCP analysis is not a clinically useful predictor of local response to pre-operative adjuvant therapy in advanced rectal carcinoma.
Authors: B Michael Ghadimi; Marian Grade; Michael J Difilippantonio; Sudhir Varma; Richard Simon; Cristina Montagna; Laszlo Füzesi; Claus Langer; Heinz Becker; Torsten Liersch; Thomas Ried Journal: J Clin Oncol Date: 2005-03-20 Impact factor: 44.544
Authors: Marian Grade; Jochen Gaedcke; Danny Wangsa; Sudhir Varma; Jaje Beckmann; Torsten Liersch; Clemens Hess; Heinz Becker; Michael J Difilippantonio; Thomas Ried; B Michael Ghadimi Journal: Cancer Genet Cytogenet Date: 2009-08