HNF1β is a sensitive and specific novel marker for yolk sac tumor: a tissue microarray analysis of 601 testicular germ cell tumors

Abstract

Hepatocyte Nuclear Factor 1 beta (HNF1) is a transcription factor which plays an important role during early organogenesis, especially of the pancreato-biliary and urogenital tract. Furthermore, HNF1 is an established marker in the differential diagnosis of ovarian cancer and shows a distinct nuclear expression in the clear cell carcinoma subtype. Recently, it has been described in yolk sac tumor, which represents a common component in many non-seminomatous germ cell tumors. Due to its broad histologic diversity, the diagnosis may be challenging and additional tools are very helpful in the workup of germ cell tumors. Immunohistochemistry was used to study HNF1 expression in a tissue microarray (TMA) of 601 testicular germ cell tumors including seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, germ cell neoplasia in situ (GCNIS), and normal tissue. The expression pattern was compared to glypican 3 (GPC3) and -fetoprotein (AFP), two markers currently in use for the detection of yolk sac tumor. HNF1 showed a distinct nuclear staining in comparison to the cytoplasmic pattern of GPC3 and AFP. The sensitivity and specificity of HNF1 were 85.4% and 96.5%, of GPC3 83.3% and 90.7%, of AFP 62.5% and 97.7%. We conclude that HNF1 allows a reliable distinction of yolk sac tumor from other germ cell tumor components. Therefore, we propose HNF1 as a novel and robust marker in the immunohistochemical workup of testicular germ cell tumors.

The pioneer and differentiation factor FOXA2 is a key driver of yolk‐sac tumour formation and a new biomarker for paediatric and adult yolk‐sac tumours

“…In this study, we highlight FOXA2 as a promising biomarker able to detect p/aYSTs with high specificity and to distinguish YST components from other GCT entities. Recently, another factor from the hepatocyte nuclear factor family (HNF1b) has been highlighted as a YST biomarker, further demonstrating the high similarity between YSTs and liver cells and suggesting that combining FOXA2 (HNF3b) and HNF1b to detect YSTs with high specificity in pathological routine diagnostics seems reasonable 51 . Additionally, FOXA2 was sensitive enough to detect few YST cells in bulk tumour masses, like classical seminomas with elevated serum AFP levels, which has an important implication for clinical use; i. e. if FOXA2 is detectable in a patient's tumour sample, early more aggressive treatment may be recommended before YST outgrowth renders these progressive treatment‐resistant GCTs incurable.…”

“…Recently, another factor from the hepatocyte nuclear factor family (HNF1b) has been highlighted as a YST biomarker, further demonstrating the high similarity between YSTs and liver cells and suggesting that combining FOXA2 (HNF3b) and HNF1b to detect YSTs with high specificity in pathological routine diagnostics seems reasonable. 51 Additionally, FOXA2…”

HNF-1β is a More Sensitive and Specific Marker Than C-Reactive Protein for Identifying Biliary Differentiation in Primary Hepatic Carcinomas

“…6 The same study also reported expression of HNF-1b in various carcinomas with cytoplasmic and/or nuclear expression, including cholangiocarcinomas (86.7%). 6 However, previous studies on renal clear cell carcinoma and urothelial carcinoma, 11 testicular yolk sac tumor, 17 ovarian clear cell carcinoma, 15 and colorectal carcinoma 13 showed only nuclear expression. In background liver, only the biliary epithelial cells show nuclear HNF-1b expression, whereas hepatocytes are negative.…”

“…[11][12][13][14][15][16] Recently, HNF-1b was recognized as a sensitive and specific marker for testicular yolk sac tumors with sensitivity and specificity of 85.4% and 96.5%. 17 Studies show that pancreatic ductal adenocarcinoma expresses HNF-1b in 75.6% to 84.3% of cases. 6 In the liver, HNF-1b expression in iCCAs and its correlation with expression of other biliary markers has been reported.…”

Diagnostic importance of hepatocyte nuclear factor 1 beta (HNF1β) in testicular tumors and its sensitivity for the detection of yolk sac tumors: an immunohistochemical analysis

“…In recent years, some studies have indicated that HNF1β may be useful in differentiating YSTs from other germ cell tumors [11,12]. In our study, we aimed to determine the role of the HNF1β immunomarker in the differentiation of different histological types through its expression profile in testicular tumors, and especially in pure YSTs and mixed germ cell tumors (MGCTs).…”