Tumor response to neoadjuvant chemotherapy correlates with the expression of P-glycoprotein and PCNA but not GST-pi in the tumor cells of cervical carcinoma.
OBJECTIVE
To identify the clinicopathological and chemoresistant factors predicting the response to neoadjuvant chemotherapy and the patient prognosis in high-risk cervical carcinomas.


METHODS
We retrospectively reviewed 47 patients with locally advanced or bulky cervical carcinoma treated with two courses of intraarterial infusion of cisplatin, doxorubicin, mitomycin C, and 5-fluorouracil (5-FU), followed by radical hysterectomy at our hospital between 1988 and 1995. Expressions of the chemoresistance-related proteins, such as P-glycoprotein, glutathione S-transferase pi (GST-pi), and proliferating cell nuclear antigen (PCNA) in the tumor cells, were examined by immunohistochemistry using pretreatment biopsy specimens. These results were compared with the chemotherapeutic response, which was evaluated by magnetic resonance imaging (MRI) and histopathology. Outcome of the patients was also studied.


RESULTS
Chemotherapeutic effect of either complete (CR) or partial (PR) response on MRI was obtained in 36 of the 47 (86%) patients. Poor response to chemotherapy was significantly correlated with P-glycoprotein expression (P < 0.005) and low PCNA labeling (P < 0. 05), but not GST-pi expression in the tumor cells. Independent prognostic factors for patient survival were parametrial involvement and lymph node metastasis. Neither the expression of GST-pi nor PCNA was correlated with the patient survival.


CONCLUSIONS
Assessment of the expression of P-glycoprotein and PCNA is potentially useful for the prediction of tumor response to neoadjuvant chemotherapy for cervical carcinomas.
Konishi
I
I
Department of Gynecology and Obstetrics, Department of Radiology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606, Japan. konishi@kuhp.kyoto-u.ac.jp
Nanbu
K
K
Mandai
M
M
Tsuruta
Y
Y
Kataoka
N
N
Nagata
Y
Y
Mori
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007044:Hysterectomy; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007527:Isoenzymes; D018809:Proliferating Cell Nuclear Antigen; D016685:Mitomycin; D004317:Doxorubicin; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D002945:Cisplatin; D005472:Fluorouracil