Carbonic anhydrase XII expression is associated with histologic grade of cervical cancer and superior radiotherapy outcome.
BACKGROUND
To investigate whether expression of carbonic anhydrase XII (CA12) is associated with histologic grade of the tumors and radiotherapy outcomes of the patients with invasive cervical cancer.


METHODS
CA12 expression was examined by immunohistochemical stains in cervical cancer tissues from 183 radiotherapy patients. Histological grading was classified as well (WD), moderately (MD) or poorly differentiated (PD). Oligonucleotide microarray experiment was performed using seven cervical cancer samples to examine differentially expressed genes between WD and PD cervical cancers. The association between CA12 and histological grade was analyzed by chi-square test. CA12 and histological grades were analyzed individually and as combined CA12 and histologic grade categories for effects on survival outcome.


RESULTS
Immunohistochemical expression of CA12 was highly associated with the histologic grade of cervical cancer. Lack of CA12 expression was associated with PD histology, with an odds ratio of 3.9 (P = 0.01). Microarray analysis showed a fourfold reduction in CA12 gene expression in PD tumors. CA12 expression was marginally associated with superior disease-free survival. Application of the new combined categories resulted in further discrimination of the prognosis of patients with moderate and poorly differentiated tumor grade.


CONCLUSIONS
Our study indicates that CA12 may be used as a novel prognostic marker in combination with histologic grade of the tumors.
Research Institute and Hospital, National Cancer Center, Goyang, Gyeonggi, Korea.
Chong Woo
CW
Yoo
Byung-Ho
BH
Nam
Joo-Young
JY
Kim
Hye-Jin
HJ
Shin
Hyunsun
H
Lim
Sun
S
Lee
Su-Kyoung
SK
Lee
Myong-Cheol
MC
Lim
Yong-Jung
YJ
Song
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002256:Carbonic Anhydrases / Q000096:biosynthesis* / Q000235:genetics; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011878:Radiotherapy; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C483903:CA13 protein, human; D002256:Carbonic Anhydrases