Altered expression of nm23-H1 and c-erbB-2 proteins have prognostic significance in adenocarcinoma but not in squamous cell carcinoma of the uterine cervix.
BACKGROUND
The reduced expression of nm23-H1 protein and/or overexpression of c-erbB-2 protein reportedly is associated with a high incidence of lymphatic metastasis or poor prognosis of the patient in a variety of human malignant tumors.


METHODS
The expression patterns of nm23-H1 and c-erbB-2 proteins were analyzed by immunohistochemical staining using formalin fixed, paraffin embedded sections of 88 cases of invasive carcinoma (39 matched pairs of adenocarcinoma and squamous cell carcinoma, 8 cases of adenosquamous carcinoma, and 2 cases of undifferentiated carcinoma) and 31 cases of preinvasive lesions of the uterine cervix.


RESULTS
Expression of nm23-H1 was detected in 46% of adenocarcinoma and in 36% of squamous cell carcinoma of the uterine cervix, whereas c-erbB-2 expression was evident in 49% and 38%, respectively. Negative expression of nm23-H1, positive expression of c-erbB-2, and a combined nm23-H1-negative and c-erbB-2-positive expression were associated with a high incidence of lymph node involvement (P = 0.36, P = 0.0015, P = 0.0055, respectively) and with poor prognosis of patients (P = 0.034, P = 0.014, P = 0.00008, respectively) with adenocarcinoma of the uterine cervix, but not in those with squamous cell carcinoma. Multivariate analysis using the Cox's proportional hazard model also revealed that these three factors significantly contributed to the prognosis of patients with cervical adenocarcinoma.


CONCLUSIONS
Reduced expression of the nm23-H1 protein, increased expression of the c-erbB-2 protein, and a combined nm23-H1-negative and c-erbB-2-positive expression have prognostic significance in patients with adenocarcinoma, whereas they may not be associated with the prognosis of squamous cell carcinoma of the uterine cervix, nm23-H1 and c-erbB-2 proteins may have different functions according to the subtype of cervical carcinoma.
Mandai
M
M
Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Japan.
Konishi
I
I
Koshiyama
M
M
Komatsu
T
T
Yamamoto
S
S
Nanbu
K
K
Mori
T
T
Fukumoto
M
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology / Q000556:secondary; D018196:Carcinoma, Adenosquamous / Q000235:genetics / Q000473:pathology / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000556:secondary*; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins; D015999:Multivariate Analysis; D054778:NM23 Nucleoside Diphosphate Kinases; D009361:Neoplasm Invasiveness; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics*; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000473:pathology
D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D018719:Erb-b2 Receptor Tyrosine Kinases; D014157:Transcription Factors; C517938:NME1 protein, human