Infection of human papillomavirus and overexpression of dihydrodiol dehydrogenase in uterine cervical cancer.
OBJECTIVE
To determine the association of human papillomavirus (HPV) infection with the expression of dihydrodiol dehydrogenase (DDH) in uterine cervical cancer (UCC).


METHODS
In situ hybridization (ISH) and immunohistochemistry were applied to examine pathological specimens of 145 patients with UCC.


RESULTS
By ISH, HPV16/18 DNA was detected in 108 (74.5%) UCC cases. DDH expression determined by immunohistochemistry was detected in 81 (75%) lesions among 108 HPV-positive cases. In contrast, of 37 HPV-negative cases, DDH was only detected in 16 (43.2%) of the lesions. A significant correlation was found between DDH expression and the presence of HPV (P < 0.001), FIGO stage (P = 0.004), lymph node involvement (P < 0.001), as well as patients' survival (P = 0.002). In vitro, DDH expression was also found closely associated with HPV infection, and DDH content was proportional to cell sensitivity for cisplatin and doxorubicin.


CONCLUSIONS
HPV infection provokes local inflammation, which can then induce DDH expression and drug resistance in UCC. The detailed biological relationship among HPV infection, expression of DDH and drug resistance, however, remains to be clarified.
Ueda
Masatsugu
M
Department of Obstetrics and Gynecology, Osaka Medical College, Osaka, Japan.
Hung
Yao-Ching
YC
Chen
Jin-Tang
JT
Chiou
Shiow-Her
SH
Huang
Hsuan-Hua
HH
Lin
Tze-Yi
TY
Terai
Yoshito
Y
Chow
Kuan-Chih
KC
D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004279:DNA, Viral / Q000032:analysis; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000201:enzymology / Q000821:virology; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D052161:Human papillomavirus 18 / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000821:virology; D010088:Oxidoreductases / Q000096:biosynthesis*; D030361:Papillomavirus Infections / Q000150:complications* / Q000201:enzymology* / Q000821:virology; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000821:virology*
D004279:DNA, Viral; D004317:Doxorubicin; D010088:Oxidoreductases; C048338:trans-1,2-dihydrobenzene-1,2-diol dehydrogenase; D002945:Cisplatin