Immunohistochemical Differences In Patients With Or Without Gonadal Malignancy

BackgroundDisorders of sex development (DSD), which affect 1 in 4,500-5,000 live births, are uncommon but not rare. Previously referred to as intersex disorders, DSD comprise a variety of anomalies defined by congenital conditions in which chromosomal, gonadal, or anatomical sex is atypical. DSD has distinct clinicopathological characteristics and biological behavior. Young patients, good prognosis and long survival period are features pertaining to DSD. Most publications were carried out in the United States and Europe while those focusing on Chinese patients are relatively few.Objectives1. Aim to set up DSD Database in our institution and analyze clinicopathological variables.2. Aim to investigate potential molecular biomarkers through immunohistochemistry in patients with or without gonadal malignancy.Methods and Materials1. A retrospective analysis of medical records of DSD patients who did the gonadal surgery in our institution over 30 years from Oct.1984 to Oct.2014 was performed to analyze the clinicopathological features and prognosis.2. Immunohistochemistry was performed in DSD tissue with or without gonadal malignancy to investigate the expression pattern of PLAP, α-inhibin, OCT4, SOX9 and FOXL2 and to explore the possible relevance to clinicopathologic parameters and prognosis.Results1.291 patients admitted in this research have a mean of 19.1 (±6.3) years, an average height of 165cm and weight of 19.98 kg/m2. The p values between tumor group and non-tumor group of these three factors are all more than 0.05.2. Sertoli cell adenomas is only found in 46,XY DSD patients and its clinical as well as immunohistochemical features are similar to other 46,XY DSD without gonadal tumour.3. Of total patients,12.0% developed gonadal tumour which preferred to be in the left side and abdominal.4. Surgery combined with PEB (cisplatin+etoposide+bleomycin) or PVB (cisplatin+ vinblastine+bleomycin) can make a 100% CR.5.28 tumor cases have a mean of 73.5 (±73.0) follow-up months.6. Quality of life (QoL) in DSD tomour patients was compromised because of a heavier psychosocial burden.7. The p value of a-inhibin, SOX9, FOXL2, OCT4 and PLAP between tumor and non-tumor group were 0.248,0.338,0.049,0.001 and <0.001. a-inhibin expression decreased in XY tumor tissues (p=0.019). The p value of FOXL2 between tumor and non-tumor group was 0.056.ConclusionsThe percentage of gonadal tumour in DSD patients is 12.0%. Age and BMI are not the risk factors. And the tumor tissue seems more likely to be the left side and locate inside the pelvis. DSD patients have a good prognosis while a compromised QoL especially the psychosocial well-being. OCT4 and PLAP can be used as molecular biomarkers of germ cell tumors while SOX9 cannot, α-inhibin expression decreased in XY tumor tissues. And there need more researchs on FOXL2’s function as a biomarker of XY tumour patients.