ABSTRACT
BACKGROUND: Not all patients with locally advanced rectal cancer (LARC) respond equally to neo-adjuvant radiochemotherapy (RCT). Patients with highly apoptotic less advanced rectal cancers do not benefit from short-term radiotherapy. This study investigates whether this is also the case in the setting of RCT for LARC. PATIENTS AND METHODS: Tissue microarrays were constructed of biopsy and resection specimens of 201 LARC patients. Apoptosis (M30) and several apoptosis-regulating proteins [p53, Bcl-2, Bax, cyclooxygenase-2 (Cox-2) and mamma serine protease inhibitor (maspin)] were studied with immunohistochemistry. Subsequently, predictive values for local recurrence (LR), overall survival (OS) and histological tumour regression were analysed. RESULTS: Apoptotic levels, quantified as the number of apoptotic cells/mm(2) tumour epithelium, were higher in posttherapy tissues compared with biopsies (P < 0.001). Biopsies from clinical T4 stage tumours demonstrated significantly higher levels of apoptosis than clinical T3 stage tumours (P = 0.020). Therapy-induced apoptosis was higher when the interval between the last day of irradiation and surgery increased (P < 0.001, correlation coefficient = 0.355). Pre- and posttherapy apoptosis, p53, Bcl-2, Bax and Cox-2 were not associated with LR, OS or tumour regression. Intense pretherapy cytoplasmatic staining of maspin indicated a higher risk on LR (P = 0.009) only. CONCLUSION: Combined RCT is also successful in highly apoptotic tumours and is therefore independent of intrinsic apoptosis.
Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/therapy , Neoadjuvant Therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Apoptosis/drug effects , Apoptosis/radiation effects , Cyclooxygenase 2/metabolism , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Proto-Oncogene Proteins c-bcl-2/metabolism , Radiotherapy , Rectal Neoplasms/mortality , Serpins/metabolism , Tissue Array Analysis , Tumor Suppressor Protein p53/metabolism , bcl-2-Associated X Protein/metabolismABSTRACT
Three patients, two men aged 54 and 72 years, respectively, and a woman aged 52 years, were treated successfully for (recurrence of a) keratoacanthoma with methotrexate. Since the sixties 11 patients with recurrent keratoacanthoma treated with methotrexate have been described. Dose schedules were widely different and dosages were in general high, resulting in more or less severe side effects. The patients now presented were treated according to the Weinstein schedule, with small doses and during a short period, which minimises the adverse effects.
