Coexpression of cholesterol sulfate and cytokeratin as tumor markers in well-differentiated squamous cell carcinoma of the human uterine cervix

The expression of cholesterol sulfate (CS) is known to increase during squa mous differentiation of keratinocytes and to activate the epsilon, eta, and zeta forms of protein kinase C as a signal transduction molecule for the s ubsequent expression of transglutaminase-l (TG-1) and cytokeratins. To gain further insight into the regulation of cellular differentiation and tumori genesis by CS, me examined the concentration and the potential for synthesi s of CS in seven and four surgical specimens from human ovarian and uterine cervical cancer patients, respectively, and eight cell lines established f rom human uterine cervical cancer patients and compared them for the rate o f expression of cytokeratin. CS was present in all of the uterine cervical cancer tissue specimens but only in the mucinous type of cystadenocarcinoma among ovarian cancer tissue specimens, and cytokeratin was highly expresse d in the tissues with a high concentration of CS, which were classified as well-differentiated on the basis of morphological examination. Similarly, c ells derived from a keratinizing type of well-differentiated cervical carci noma demonstrated strong potential for synthesis of CS, stained positive wi th anti-cytokeratin antibody, and exhibited a higher specific activity of T G-I, whereas the cells without CS did not stain positive with anti-cytokera tin antibody and exhibited a lower specific activity of TG-1, These finding s indicate that CS is coexpressed with TG-1 and cytokeratin in the well-dif ferentiated types of squamous cell cancers as a tumor marker.