Germline epimutations of <i>APC</i> are not associated with inherited colorectal polyposis: Figure 1

GIST, first operated on 13 years earlier, and who now presented with four adjacent masses located in the rectovaginal septum and no distant metastasis.Molecular analysis identified a 6 bp deletion in exon 11 of the ckit proto-oncogene.As curative surgery would have implied abdominoperineal resection with permanent colostomy, treatment with imatinib at a standard dose (400 mg/ day) was started.Response to treatment was evaluated using endorectal ultrasound and magnetic resonance imaging every three months.Quantification of tumour mass was obtained by adding the products of two perpendicular axes of the two major lesions.Maximal response was obtained at nine months, which was maintained after 12 months of treatment.At that time, total tumour mass reduction was 83%, which was enough to allow rectal resection with a coloanal anastomosis (fig 1A, B).Pathological analysis of the surgical specimen identified four white firm masses with diameters ranging from 1 to 2 cm.These lesions were composed of hyaline connective tissue, which did not stain with either CD34 or CD117, and no viable tumour cells were identified in the whole specimens (fig 1C-E).Imatinib was suspended and after 24 months of follow up there is no evidence of local or distant recurrence.This is, to our knowledge, the first report of a complete pathological response of a GIST treated with imatinib.Most GISTs have been shown to have activating mutations of the c-KIT or PDGF receptor alpha (PDGFRA) proto-oncogenes which result in constitutive activation of a tyrosine kinase.2 3 The main treatment for GIST is, whenever possible, based on surgical resection, as these tumours are resistant to chemotherapy and radiation therapy.For tumours which are not amenable to surgical resection, a selective tyrosine kinase inhibitor, imatinib (Glivec; Novartis, Basel, Switzerland), is actually the firstline treatment as it specifically inhibits most c-KIT and PDGFRA activated proteins.Preliminary results using imatinib treatment were very satisfactory, with greater than 50% reduction of tumour mass reported in 54% of cases.4 Although to date no data support the use of imatinib as neoadjuvant therapy, the last consensus meeting for the management of GISTs 5 suggests that this form of therapy may be used for tumours with certain locations (for example, rectum, or oesophagus), when function sparing surgery is the goal.Our case report is consistent with a recently published multicentre randomised trial involving 946 patients who received imatinib for local, advanced, or metastatic GIST.6 In this study, the authors observed that the time needed to achieve maximal response was 4-6 months, thereby recommending that studies on neoadjuvant therapy should be designed with a duration of treatment ranging from 4 to 6 months, which could be extended up to one year.The present report further supports these recommendations, mainly in cases with typical activating mutations and in those in whom surgery would lead to a marked loss of organ function.

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