RAD6 Overexpression and Ovarian Cancer Chemo-Resistance: Flow Cytometry and Immunohistochemistry

Objective: Ovarian cancer is one of the deadliest women’s cancers in the world. Nearly all the patients have poor prognosis and recurrence after standard therapy because of chemo-resistance. The standard therapy is cytoreductive debulking surgery followed by platinum-based chemotherapy. RAD6 has an important role in chemo-resistance. RAD6 is an E2 Ubiquitin-Conjugating Enzymes (UBE2) enzyme required for DNA repair, cell proliferation, and cell mutagenesis. Increased expression of RAD6 is believed to be associated with chemoresistance, recurrence, and poor prognosis of the disease. We aimed to study RAD6 relationship with ovarian cancer chemo-resistance and its ability to predict chemo-resistance.

Methods: This study is an ambispective cohort study of 32 people in each group at the obstetrics-gynecology and pathology Department of Cipto Mangunkusumo, Tarakan, Dharmais, and Fatmawati Hospital. All patients will undergo standard cytoreductive debulking and histopathological examination followed by six series of chemotherapy followed by six months of observation. After the observation, we determine therapy response with the RECIST Criteria (Response Criteria in Solid Tumors). The chemo-resistance and chemo sensitive groups will be analyzed according to the therapy response. Our study is the first study examining RAD6 in ovarian cancer from flow cytometry blood test and directly from ovarian cancer tissue by double immunohistochemistry.

Results: We found a significant relationship between increased levels of RAD6 expression (p<0,05) with chemoresistance of ovarian cancer in both studies while immunohistochemistry has a better multivariate analysis result.

Conclusion: Both studies indicate that RAD6 is a significantly correlated and good chemo-resistance predictor for ovarian cancer chemo-resistance while RAD6 immunohistochemistry is a better predictor.