Does Human Epididymis Protein 4 (HE4) Have a Role in Prediction of Recurrent Epithelial Ovarian Cancer.

BACKGROUND: Despite the fact that ovarian cancer is the seventh most common cancer in women worldwide and the fth leading cause of cancer death, It is the most common cause of death due to reproductive cancers in Thailand where epithelial ovarian cancer (EOC) is commonly found. According to a Thai statistical analysis in 2010 by the Department of Medical Services, epithelial ovarian cancer was the sixth most common cancer in Thailand from 2001 to 2003.The incidence of 5.1 per 100,000 women per year. Human epididymis protein 4 (HE4) is a novo diagnostic tumor marker for EOC. The combination of HE4 and carcinoma antigen 125 (CA 125) is a tool for detecting epithelial ovarian cancer (EOC) better than using CA 125 alone. Therefore, the researcher is interested in HE4 does have a role to predict recurrent epithelial ovarian cancer. MATERIALS AND METHODS: The patients who had complete response after diagnosed with epithelial ovarian cancer by pathology, FIGO stage 3 or more had been treated through surgery and chemotherapy at the Sunpasitthiprasong Hospital from June 2014 until March 2016. The patients were followed up every three months, using tumor marker (CA 125, HE4,Carcinoma antigen 19-9) together with other checkup methods, such as rectovaginal examination, CXR every year and other imaging as indication. Afterwards, the data was analyzed for the ability of HE4 to detect recurrence of epithelial ovarian cancer. RESULTS: In 47 patients in this study follow-up for 22 months after complete response treatment from surgery and chemotherapy in epithelial ovarian cancer, 23 had recurrent disease and HE4 titer rising .The patients with recurrent epithelial ovarian cancer demonstrated high levels of both HE4 and CA125 with sensitivity of 91.3% and 52.7% respectively, speci city of 87.5% and 95.6% and positive predictive values of 87.5% and 85.7% . HE4 can predict recurrent epithelial ovarian cancer (p-value=0.02242). Comparing HE4 and CA125 in predicting recurrent epithelial ovarian cancer HE4 had more potential than CA125 (p-value =0.8314). CONCLUSIONS: The present study showed HE4 to have a role in predicting recurrent epithelial ovarian cancer and HE4 is potentially better than CA125 as a marker for this purpose.

Immunocytochemical staining of p16INK4a protein from conventional Pap test and its association with human papillomavirus infection.

The p16INK4a protein is immunocytochemically detected in liquid-based (LB) specimens as a diagnostic marker of cervical dysplasia and neoplasia. Its up-regulation is promoted by high-risk human papillomavirus (HR-HPV) infection. We aimed to detect p16INK4a on conventional Papanicolaou (Pap) test (CPT) slides and to determine the relationship between its overexpression and HR-HPV infection. CPT and LB Pap test (LBPT) slides (165 samples of each) were examined by immunocytochemical staining for p16INK4a. After polymerase chain reaction (PCR), HPV-DNA was genotyped by dot blot hybridization. The CPT slides displayed more numerous dispersed squamous cells and LBPT slides had a clearer background. Positive p16INK4a on CPT occurred in 0% (0/30), 52.5% (21/40), 54.3% (19/35), 100% (30/30), and 100% (30/30) in normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesions (LSILs), high-grade SILs (HSILs), and squamous cell carcinomas (SCCs) cases, respectively. LBPT slides showed comparable results but were less sensitive. HPV-DNA was detected in 86.7, 70, 45, 57.14, and 10% in SCCs, HSILs, ASCUS, LSILs, and normal cervical cells, respectively. Because HR-HPV was identified in all HPV+ samples of high-grade dysplasia (HSILs and SCCs) and all positive p16INK4a samples infected with HR-HPV, the association of p16INK4a overexpression with HR-HPV infection was confirmed. This study suggests that immunocytochemical staining of p16INK4a on CPT slides is convenient and cost-effective for cervical cancer screening by the detection of dysplastic cells infected with HR-HPV.

Usefulness of combining testing for p16 protein and human papillomavirus (HPV) in cervical carcinoma screening.

OBJECTIVE: To evaluate the value of the combination of p16 and HPV detection in the screening for cervical cancer. METHODS: 186 patients with previous abnormal cervical lesion were studied. After colposcopic examination, two conventional Pap slides were prepared: the first was Papanicolaou-stained and examined by cytologist; the second was immunocytochemically stained for p16. Cervical cells were collected by brush using for HPV detection by Hybrid Capture II. Biopsy of any colposcopically abnormal lesions was performed. RESULTS: The 186 cervical samples were classified cytologically as normal (148), ASCUS (13), low-grade (11), high-grade (12) dysplasia and squamous cell carcinoma (2). P16 and HPV were found in all high-grade dysplasia and SCC, and in 64% and 27% of low-grade dysplasia, 62% and 0% of ASCUS and 7.4% and 3.4% of normal, respectively. 18 of p16-positive cases (11%) were HPV-negative, 14 of them in the ASCUS and normal group. Compared to histological results, all of the p16-positive cases of squamous metaplasia, CIN II/III and SCC were HR-HPV-positive. Therefore, the cases that were positive for both with normal cytology (5 cases) or low-grade dysplasia (3 cases) may comprise a high-risk group for neoplastic change. CONCLUSION: The combination of p16 and HPV detection may be useful in cervical cancer screening to identify high-risk patients requiring early and proper management.