Predictive effect of p53 and p21 alteration on chemotherapy response and survival in locally advanced adenocarcinoma of the esophagus.
BACKGROUND
Cell cycle regulating proteins (p53/p21) and proliferation index Ki-67 have been associated with prognosis and response to chemotherapy. The aim of this study was to determine the significance of these molecular markers on tumor response and prognostic effect in a group of esophageal cancer patients treated with neoadjuvant chemotherapy.


METHODS
Immunohistochemical expression of p53/p21 and Ki-67 was examined in pre-treatment biopsy specimen of 30 patients, in phase II neoadjuvant studies for locally advanced adenocarcinoma of the esophagus, who underwent surgery. Seven patients (23%) had progressive disease. Resection was achieved in all responders (n=23; 77%) and histochemical expression of the above-mentioned proliferating markers was examined in pre-treatment and resection specimens after chemotherapy.


RESULTS
Responders had a significantly better survival compared to non-responders (p=0.001). Expression of p53, p21 and high Ki-67 in pre-treatment specimens was 73% (22/30), 63% (19/30) and 30% (10/30), respectively and was not related to response to chemotherapy. However, alteration in expression of p53-positivity in the pre-treatment specimens to p53-negativity in the resection specimens and p21-negativity to p21-positivity in 6 of the 23 (26%) resected tumors was correlated with better response and survival (p=0.011).


CONCLUSIONS
Data from this study showed that alteration of p53 and p21 expression rather than the initial expression seems to be related to chemotherapy response and overall survival in patients with esophageal adenocarcinoma.
Department of Surgical Oncology, University Hospital Groningen, Groningen, The Netherlands.
Pierre A M
PA
Heeren
Frank W H
FW
Kloppenberg
Harry
H
Hollema
Nanno H
NH
Mulder
Raoul E
RE
Nap
John Th M
JT
Plukker
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017322:Clinical Trials, Phase II as Topic; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011237:Predictive Value of Tests; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53