Spontaneous and inducible apoptosis in oesophageal adenocarcinoma.
The use of neoadjuvant chemoradiotherapy prior to surgery in the treatment of oesophageal adenocarcinoma has increased in recent years, and up to 25% of patients will have a complete pathological response to the neoadjuvant therapy. Many patients will not respond, however, and the knowledge of molecular factors predicting response or resistance to chemoradiotherapy is required to enhance treatment results. An understanding of apoptosis and cell proliferation may be relevant and this study focused on apoptotic indices and cell-cycle related (Ki-67, p53 and bcl-2) protein expression in a cohort of 42 patients with primary oesophageal adenocarcinoma. We documented that apoptosis occurs among viable (proliferating) tumour cells in all adenocarcinoma cases examined in this study. Pre-operative chemoradiotherapy significantly increased apoptosis and significantly decreased cell proliferation (estimated by Ki-67 expression). Immunohistochemically detected p53 and bcl-2 gene products had no regulatory role in the apoptotic process. The cumulative expression of p53 protein is significantly associated with increasing proliferation activity. Evaluation of apoptosis in pre-treatment specimens may have potential utility in predicting the efficacy of treatment. Assessment of the tumours proliferation activity by Ki-67 expression might identify patients who are at risk of developing metastatic disease.
Raouf
A
A
The Department of Clinical Surgery, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
Evoy
D
D
Carton
E
E
Mulligan
E
E
Griffin
M
M
Sweeney
E
E
Reynolds
J V
JV
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000378:metabolism / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D011878:Radiotherapy; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin; D005472:Fluorouracil