Primary mediastinal germ cell tumors (GCTs) are rare and sometimes they pose diagnostic difficulty without immunohistochemical studies. Here, we investigated the diagnostic utility of 6 stem cell markers (SCMs) SALL4, OCT4, NANOG, SOX2, UTF1, and TCL1 in 16 primary mediastinal seminomas, 3 embryonal carcinomas (ECs), 10 yolk sac tumors (YSTs), 7 teratomas (4 mature, 3 immature), and 1 choriocarcinoma. The percentage of tumor cells stained was scored as: 0 (no tumor cell staining), 1+ (< or =30%), 2+ (31% to 60%), 3+ (61% to 90%), and 4+ (>90%). The staining intensity of SCMs was scored as weak, moderate, or strong. We also compared them with currently used GCT markers placental-like alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), c-KIT, CD30, and glypican-3. All 16 seminomas showed staining for SALL4 (4+ in 15, 2+ in 1) (15 strong, 1 moderate), OCT4 (4+ in 11, 3+ in 4, 2+ in 1) (13 strong, 3 moderate), and UTF1 (4+ in 13, 3+ in 2, 2+ in 1) (7 strong, 5 moderate, 4 weak). Positive staining was shown by 9/9 seminomas tested for NANOG (4+ in 7, 2+ in 2) (8 strong, 1 weak), TCL1 (4+ strong in all), c-KIT (4+ in all), and PLAP (4+ in 5, 3+ in 1, 2+ in 2, 1+ in 1), but SOX2 staining was negative in all these tumors. All 3 ECs showed 4+ strong staining for SALL4, OCT4, and UTF1 but negative for TCL1. SOX2 staining was seen in 3/3 ECs (4+ strong in 1, 3+ weak to moderate in 2) whereas NANOG staining was seen in 2/3 ECs (2+ weak, 1+ moderate). CD30 staining was seen in 3/3 ECs (1+, 2+, 4+). Strong SALL4 staining was seen in 10/10 YSTs (4+ in 9, 2+ in 1). All 10 YSTs showed AFP (1+ in 7, 2+ in 1, 3+ in 2) and glypican-3 (1+ in 3, 2+ in 1, 3+ in 5, 4+ in 1) staining but only 4/10 YSTs showed PLAP staining (1+ in all 4). The mean percentage of YST cells stained with SALL4 was 92%, whereas it was 23% for AFP, 50% for glypican-3, and 4% for PLAP (P<0.01). Focal (1+) SALL4 (weak) and SOX2 (weak to moderate) staining was seen in 2/7 and 4/7 teratomas, respectively. The choriocarcinoma was negative for all 6 SCMs. Eleven thymomas and 6 thymic carcinomas were negative for 6 SCMs. No staining of NANOG and SOX2 was seen in 20 lymphomas (5 Hodgkin, 5 large B cell, 5 lymphoblastic, 5 anaplastic large cell) (other 4 SCMs in lymphomas earlier studied). Our study indicates that SALL4, OCT4, NANOG, SOX2, UTF1, and TLC1 are novel sensitive diagnostic markers for primary mediastinal GCTs, with high specificity. Of these 6 SCMs, SALL4 is the only 1 expressed in YST. These novel SCMs are more sensitive than the currently used markers for mediastinal GCTs.
LIN28 has been shown to have an important role in primordial germ cell development and malignant transformation of germ cells in mouse. In this study, we examined the immunohistochemical profile of LIN28 in 131 primary human extragonadal germ cell tumors (central nervous system (CNS) 76, mediastinum 17, sacrococcygeal region 30, pelvis 3, vagina 2, liver 1, omentum 1, and retroperitoneum 1), including the following tumors and/or components: 57 seminomas/germinomas, 10 embryonal carcinomas, 74 yolk sac tumors, 6 choriocarcinomas, 15 mature, and 13 immature teratomas. We compared LIN28 with SALL4 to assess its diagnostic value. To determine its specificity, we examined LIN28 in 406 extragonadal-non-germ cell tumors (103 carcinomas, 91 sarcomas, 9 melanomas, 12 mesotheliomas, 83 lymphomas, 9 plasmacytomas, 82 CNS tumors, and 17 thymic epithelial tumors). The staining was semi-quantitatively scored as 0 (no cell stained), 1 þ (0-30%), 2 þ (31-60%), 3 þ (61-90%), and 4 þ (490%). LIN28 staining was seen in all seminomas/germinomas (3 þ in 1 and 4 þ in 56), embryonal carcinomas (4 þ in all 10), and yolk sac tumors (3 þ in 3 and 4 þ in 71). Variable LIN28 staining was seen in 5 of 6 choriocarcinomas (1 þ to 4 þ ), 8 of 13 immature teratomas (1 þ to 2 þ in immature elements), and in 1 of 15 mature teratomas (1 þ ). Only 11 of 406 non-germ cell tumors showed 1 þ LIN28 staining. Therefore, LIN28 is a sensitive (100% sensitivity) marker for primary extragonadal seminomas/germinomas, embryonal carcinomas, and yolk sac tumors with high specificity. Compared with SALL4, LIN28 demonstrated a similar level of diagnostic sensitivity for seminomas/ germinomas and embryonal carcinomas. For primary extragonadal yolk sac tumors, although SALL4 stained all tumors (1 þ in 1, 2 þ in 2, 3 þ in 10, and 4 þ in 61), LIN28 stained more tumor cells (mean 95 vs 90%, P ¼ 0.03) and was therefore more sensitive. For primary extragonadal yolk sac tumors, combining LIN28 and SALL4 can achieve a higher diagnostic sensitivity than either alone.
Purpose To predict miscarriage outcome within 12 weeks of gestational age by evaluating values of serum estradiol, progesterone and β-human chorionic gonadotropin (β-HCG) within 9 weeks of gestation. Methods One hundred sixty-five women with singleton pregnancies were retrospectively studied. Estradiol, progesterone and β-HCG levels were measured at 5–6 weeks of gestation and the measurements were repeated at 7–9 weeks. According to pregnancy outcome at 12 weeks of gestation, 71 cases were categorized into miscarriage group, and 94 cases into group of normal pregnancy. Each group was further divided into 5–6 and 7–9 weeks of gestation sub-group. Predictive values of estradiol, progesterone and β- HCG levels at 5–6 weeks and 7–9 weeks of gestation were analyzed with receiver operating characteristic (ROC) curves and logistic regression. Results Serum levels of estradiol at 7–9 weeks identified miscarriage with an area under the ROC curve (AUC) of 0.866 (95% CI 0. 793 ~ 0.938, P = 0.000), diagnostic cutoff value of 576 pg/ml, sensitivity of 0.804, and specificity of 0.829 respectively at the optimal threshold, according to Youden index. Progesterone levels at 7–9 weeks were with AUC of 0.766 (95% CI 0. 672 ~ 0.861, P = 0.000), cutoff value of 15.27 ng/ml, sensitivity of 0.921, and specificity of 0.558, respectively; Estradiol at 5–6 weeks were with AUC of 0.709 (95% CI 0. 616 ~ 0.801, P < 0.001), the diagnostic cutoff value of 320 pg/ml, sensitivity of 0.800, and specificity of 0.574, respectively. The performance of the dual markers of estradiol and progesterone analysis (AUC 0.871, CI 0.793–0.950), three-markers analysis (AUC 0.869, CI 0.759–0.980)were slightly better than the single marker at 7-9 weeks. β-HCG or progesterone provide additional utility of estradiol prediction at 5–6 weeks with AUC 0.770 (0.672–0.869) for β-HCG and estradiol, AUC0.768(CI 0.670–0.866) for β-HCG, estradiol and progesterone and AUC 0.739 (CI 0.651–0.827) for progesterone and estradiol. Conclusions Low serum levels such as dual of estradiol and progesterone or estradiol alone at 7–9 weeks, β-HCG or progesterone combing estradiol at 5–6 weeks of gestation can be used better to predict miscarriage in first trimester.
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