Abstract
BackgroundTo 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.MethodsCA12 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.ResultsImmunohistochemical 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.ConclusionsOur study indicates that CA12 may be used as a novel prognostic marker in combination with histologic grade of the tumors.
Highlights
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
Histological grading is frequently open to considerable subjectivity among the observers [6,7,8] and it is commonly known that only about 20%-30% of examined specimens are clearly classified as WD or poorly differentiated (PD), with the majority tumors being left in the MD category [6,7,8]; MD category encompasses tumors with varying clinical behaviour
When CA12 expression was introduced into the conventional histologic grading system, both the prognosis of MD and PD tumors were shown to be influenced by CA12 expression
Summary
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. CA12 is one of the tumor-associated antigens known to be overexpressed under hypoxic conditions. Overexpression of CA12 is observed in von Hippel-Lindau(VHL)defective tumor cells with CA9, and is believed to contribute in an acid extracellular PH in malignant tumors [1,2]. The conventional histological grading of epithelial carcinoma is determined by the microscopic features which represent the extent of similarity of tumor cells to normal cells. These features include mitotic activity, nuclear pleomorphism, and nucleo-cytoplasmic ratio of the cancer cells. Histological grading is frequently open to considerable subjectivity among the observers [6,7,8] and it is commonly known that only about 20%-30% of examined specimens are clearly classified as WD or PD, with the majority tumors being left in the MD category [6,7,8]; MD category encompasses tumors with varying clinical behaviour
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