Correlation between responsiveness of neoadjuvant chemotherapy and apoptosis-associated proteins for cervical adenocarcinoma.
OBJECTIVE
Adenocarcinoma of the uterine cervix appears to be increasing in prevalence and it has been suggested that these tumors tend to be less sensitive to radiation therapy and to chemotherapy than squamous carcinomas. In the present study, 29 patients with locally advanced cervical adenocarcinoma (bulky IB-IVB) were treated with neoadjuvant chemotherapy (NAC) using cisplatin, aclacinomycin-A and mitomycin-C, followed by radical surgery or irradiation.


METHODS
To predict the prognosis and response to the chemotherapy, the expression of apoptosis associated-proteins, p53, p21WAF1/CIP1, Bcl-2 and activated caspase-3 was evaluated for tumor samples by immunohistochemistry.


RESULTS
Of the analyzed clinicopathological factors, the overexpression of p53 was frequently observed in endocervical-type adenocarcinoma, nonresponders to chemotherapy and the grade 0 histologic effect of the chemotherapy. Positive staining of Bcl-2 was frequently observed in the early stage and had a better prognosis than for patients with the negative staining; however, there was no correlation between responders and nonresponders to chemotherapy. The expression of p21WAF1/CIP1 and caspase-3 was not correlated to the clinicopathological factors.


CONCLUSIONS
In this study, the overexpression of p53 was found to be a factor to predict the chemoresistance and positive expression of Bcl-2 indicated as a better prognostic value. For p21WAF1/CIP1 and caspase-3, further analysis is necessary.
Saito
Tsuyoshi
T
Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, S-1, W-16, Chuo-ku, Sapporo 060-8543, Japan. tsaito@sapmed.ac.jp
Takehara
Masaki
M
Tanaka
Ryoichi
R
Lee
Rong
R
Horie
Miyabi
M
Wataba
Koya
K
Ito
Eiki
E
Kudo
Ryuichi
R
D015250:Aclarubicin / Q000008:administration & dosage; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000532:radiotherapy / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D002945:Cisplatin / Q000008:administration & dosage; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D020360:Neoadjuvant Therapy; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000532:radiotherapy / Q000601:surgery
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D016685:Mitomycin; D015250:Aclarubicin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin