Cervical Acid Phosphatase: A Biomarker of Cervical Dysplasia and a Potential Surrogate Endpoint for Colposcopy

Abstract

Abstract.Background: In 2000, cervical acid phosphatase (CAP) has been recently described as a biomarker labeling abnormal squamous cells on Pap smears (USPTO #6,143,512). The enzyme activity is presented as a red, granular deposit on a modified Papanicolaou background. This unique property was utilized for development of MarkPap technology intended for cervical cancer screening. Material/patients & methods:We conduct a multicenter, random assignment, assessor blinded, 2-group (test and control), splitsample designed clinical trial on 1,500 subject/specimens to assess safety and efficacy of the new test, in comparison with the control, for cervical cancer screening in standard Pap test environment. Safety is measured with frequency, severity and relation of adverse events. Efficacy is measured with primary endpoints (portion of positive/abnormal specimens detected, and the false negative rate). At the end of the follow-up period (two years) when the study will be completed, other efficacy endpoints such as accuracy (sensitivity/specificity) and predictive values will be added to the method evaluation. Here we present in interim analysis. Results: In April 2003, the recruitment was completed and the first twelve hundred cases have been evaluated. There was no serious or related adverse event in both groups. Minor, unrelated adverse events were rare and insignificantly distributed in both groups. . OR = 2.26. χ 2 = 40.69101 is greater than the critical value of 3.841 (P < 0.01). Conclusion: We concluded that CAP had added to visibility of Pap test and has enabled cytoscreeners to significantly improve the detection of positive/abnormal specimens and reduce false negative rate. We discuss this unique property of CAP with emphasis on using it as a surrogate endpoint for colposcopy and eventual removal of a cervical lesion that, if untreated, could progress into cancer.

Phosphatase‐Triggered Fusogenic Liposomes for Cytoplasmic Delivery of Cell‐Impermeable Compounds

“…[8][9][10][11][12][13] Interestingly, phosphatases are overexpressed in a number of inflammatory and chronic disorders, [14][15][16] especially in tumor microenvironments. [17,18] The broad range of phosphatases in the body and their selective over-expression in diseased tissue make them an attractive enzymatic trigger for drug carriers. [13,19] As a result, phosphatases have been used for decades as a trigger mechanism for the activation of prodrugs whose water solubility is increased by the attachment of a phosphate.…”

Cervical Acid Phosphatase: Evaluation as an Adjuvant to Papanicolaou Smear Screening in Cervical Cancer Detection

“…In our study we found that the slide positive rate increased on doing CAP as compared to PAP from 4.79% to 6.16% similar results were obtained by O Markovic et al (24) from 0.049% to 0.157% in another study (25) there was doubling of positive slides from13% to 27%. In another study Markovic O et al (17) 16.6% of the slides were positive in CAP as compared to 8.2% in PAP. In order to find out if there was difference in CAP and PAP smears examined, we tested the agreement between the two.…”

“…(14,15) By using an azo dye diazonium salt technique it was observed that demonstration of acid phosphatase activity inside abnormal cervical cells could be demonstrated. (16,17,18) Many human cell types and tissues contain acid phosphatase. In humans, acid phosphatase is confined inside lysosomes.…”

Diagnostic value of acid phosphatases (ACP) in differentiating reactive mesothelial cells from cancer cells in the body fluid effusions

“…Goto et al found that the serum ACP level was increased in giant cell tumor of bone (GCT, benign) and claimed that the ACP could be used as a tumor marker for GCT (12). Markovic et al reported that the ACP was useful as a tumor marker for screening cervical intraepithelial lesions on Pap smears (13). ACP was also used as a diagnostic marker for adult-onset Pompe disease when typical vacuolated fibers were absent (14).…”