Cancer Stem Cells (CD44+/CD24-), RAD6, DDB2 Immunohistochemistry Expression and IHC-UNEDO Scoring System As Predictor of Ovarian Cancer Chemoresistance.

Backgrounds: Ovarian cancer is a deadly women cancer with many chemoresistance after standard treatment. Ovarian cancer tissues' CD44+/CD24- (CSCs), RAD6 overexpression and DDB2 underexpression are associated with chemoresistance, recurrence, and poor prognosis of the disease because of the existence of cancer stem cells (CSCs). We tried to analyze the expression of those three proteins while building a predictor scoring system to predict the ovarian cancer chemoresistance from the ovarian cancer tissue immunohistochemistry. Materials and Methods: We conducted a cohort study of 64 patients divided into two groups (32 patients in each group) at the Cipto Mangunkusumo, Tarakan, Dharmais, and Fatmawati Hospital which are located in Jakarta city, Indonesia. The patients underwent cytoreductive debulking and histopathological examination continued by six series of chemotherapy followed by six months of observation. We divided the groups into chemoresistant and chemosensitive by using Response Criteria in Solid Tumors (RECIST) criteria. Ovarian cancer tissue immunohistochemistry tests were then performed to count the CSCs, RAD6 and DDB2 expressions. Results: We found relationship between increased CSCs, RAD6 and reduced DDB2 (p < 0.05) expression in ovarian cancer tissue with the chemoresistance. A possible predictor scoring system named IHC-UNEDO scoring was built to aid the ovarian cancer chemoresistance prediction. Conclusions: The conclusion is that CSCs, RAD6 and DDB2 expressions are significantly associated with ovarian cancer chemoresistance, and IHC-UNEDO scoring should be considered as a tool to predict ovarian cancer chemoresistance.

CD44+/CD24- Expression as predictors of ovarian cancer chemoresistance: immunohistochemistry and flow cytometry study.

BACKGROUND: The conventional standard treatment for ovarian cancer is not very effective, and the disease is fatal for women. Cancer Stem Cells (CSCs) that express CD44+/CD24- can contribute to chemoresistance and a poor prognosis. We seek to investigate the expression of CSCs (CD44+/CD24-) in ovarian cancer and their predictive significance. METHODS: The ambispective cohort was performed on 64 patients (32 patients in each group) at four hospitals (Cipto Mangunkusumo, Tarakan, Fatmawati, and Dharmais Hospital). Debulking surgery was performed on the patients, followed by histopathological analysis. The patients had six rounds of chemotherapy and were under monitoring for six months. The therapeutic responses were evaluated using the RECIST criteria (Response Criteria in Solid Tumors) and categorized as chemoresistant or chemosensitive. Using immunohistochemistry, we directly assess the CSCs from ovarian cancer tissue and using flow cytometry to assess the CSCs from the blood. RESULTS: High CSCs expression and ovarian cancer chemoresistance were significantly related in both trials (p 0.05). A better outcome was obtained using CD44+/CD24- immunohistochemistry. CONCLUSIONS: We conclude that there is a substantial association between high CSCs expression and chemoresistance in ovarian cancer and that CSCs immunohistochemistry has a higher predictive value.

Expression of CD44+/CD24-, RAD6 and DDB2 on chemotherapy response in ovarian Cancer: A prospective flow cytometry study.

Backgrounds: Ovarian cancer is the 8th deadliest common cancer in women around the world. Almost all ovarian cancer patients would experience chemoresistance, recurrence, and poor prognosis after cytoreductive surgery and platinum-based chemotherapy. Chemoresistant cancer cells have characteristic expressions of cancer stem cell proteins (CSCs) CD44+/CD24-, RAD6 and DDB2. The increased expression of CD44+/CD24-, RAD6, and decreased DDB2 are believed to be associated with chemoresistance, recurrence, and poor prognosis of the disease. Thus, this study's objective is to analyze the correlation between the expression of CD44+/CD24-, RAD6 and DDB2 with ovarian cancer chemoresistance. Materials and methods: This study was conducted with a prospective cohort of 64 patients who is divided into two groups (32 patients in each group) at the Obstetrics-gynecology and pathology department of Cipto Mangunkusumo, Tarakan, Dharmais, and Fatmawati Hospital. All suspected ovarian cancer patients underwent cytoreductive debulking and histopathological examination. Chemotherapy was given for six series followed by six months of observation. After the observation, we determined the therapy's response with the RECIST Criteria (Response Criteria in Solid Tumors) and then classified the results into chemoresistant or chemosensitive groups. Flow cytometry blood tests were then performed to examine the expression of CD44+/CD24-, RAD6 and DDB2. Results: There was a significant relationship between increased levels of CD44+/CD24-, and RAD6 (p < 0.05) levels with the chemoresistance of ovarian cancer. The logistic regression test showed that the CD44+/CD24- was better marker. Conclusions: These results indicate that CD44+/CD24 and RAD6 expressions are significantly associated with ovarian cancer chemoresistance, and CD44+/CD24- is the better marker to predict ovarian cancer chemoresistance.

Decidual infiltration of FoxP3⁺ regulatory T cells, CD3⁺ T cells, CD56⁺ decidual natural killer cells and Ki-67 trophoblast cells in hydatidiform mole compared to normal and ectopic pregnancies.

Hydatidiform moles are considered pre-cancerous lesions of gestational trophoblastic neoplasia and are associated with an aberrant immune response. This preliminary study aimed to evaluate the feasibility of measuring the presence of immune cells as potential prognostic markers for hydatidiform moles. Immunohistochemical staining of FoxP3⁺ regulatory T cells, CD3⁺ T cells, CD56⁺ decidual natural killer cells and Ki-67⁺ trophoblast cells was performed on 32 samples. Samples were from complete hydatidiform moles, partial hydatidiform moles, ectopic pregnancies, gestational age-matched normal elective pregnancy terminations (normal pregnancies) and gestational trophoblastic neoplasias. FoxP3⁺ regulatory T-cell infiltration was highest in the complete hydatidiform moles and lowest in the normal pregnancy samples. The normal pregnancy cases showed significantly fewer FoxP3⁺ regulatory T cells compared to the ectopic pregnancy cases (p=0.037) and compared to the combination of all of the other groups (p=0.044). Normal pregnancy samples also showed the lowest infiltration of CD3⁺ T cells and the highest number of CD56⁺ decidual natural killer cells; conversely, gestational trophoblastic neoplasias showed the highest infiltration of CD3⁺ T cells and the lowest number of CD56⁺ decidual natural killer cells. The numbers of Ki-67⁺ trophoblast cells were highest in the gestational trophoblastic neoplasias (688/1,000 trophoblast cells) and lowest in the partial moles (87/1,000 trophoblast cells). Our results suggest that regulatory T cells may be involved in the progression of complete hydatidiform moles. A larger cohort study is required to assess whether immune cells are effective prognostic markers in gestational trophoblastic diseases.