Identification of Two Molecular Groups of Seminomas by Using Expression and Tissue Microarrays

Abstract

Highly effective tailored clinical management of testicular germ cell tumors is based on the identification of two major histologic subtypes: seminomatous and nonseminomatous germ cell tumors. Expression array analysis of these two histologic subtypes using hierarchical clustering reveals two tumor groups, one composed solely of seminomas and the other containing embryonal carcinomas and seminomas. Supervised analysis between these groups identified 55 significantly dysregulated genes (false discovery rate = 2.3).The genes with the highest overexpression in the first group compared with the second included SLC43A1 (POV1), NET-7, IGF2, and JUP ; down-regulated genes included GRB7, PFKP, and CDC6. In situ hybridization of SLC43A1mRNA showed significantly increased signal intensity in the seminomas. At the protein level, expression of the immunohistochemical markers cytokeratins (pan-cytokeratin staining), placental-like alkaline phosphatase, anti-cytokeratin clone 5.2, CD30, anion exchanger 1/3, junction plakoglobulin (JUP), and POU domain, class 5, transcription factor 1 (octomer-binding transcription factor 3/4) was significantly different between seminomas and embryonal tumors. Hierarchical clustering based on a refined protein expression profile identified two groups, the first consisting solely of seminomas the other of seminomas and embryonal carcinomas. No histomorphologic differences were observed between the two seminoma groups such as the presence or absence of lymphocytes or extent of stromal elements. In summary, using independent methodologies and samples, we have identified two groups of seminomas. One group of seminomas has a molecular profile similar to embryonal carcinoma.The findings in the current study may help explain aberrant immunoprofiles seen with some seminomas.Testicular germ cell tumors (TGCT) are the most common solid tumor in young men aged between 20 and 35 years and over the last several decades their incidence has increased (1, 2). Seminomas account for f50% of all TGCT. Both seminomas and nonseminomatous tumors are believed to arise from carcinoma in situ of the testis (3) and currently there are two models that describe their further development. One model suggests that seminomas and nonseminomatous tumors are derived independently from carcinoma in situ, whereas the other model suggests a continuum with semi-

An oncofetal and developmental perspective on testicular germ cell cancer

“…Concordance rates between the allelic patterns were higher for CIS vs SE and SE vs EC than for CIS vs EC. This suggests possible progression from CIS to SE to EC [125], a rare transition in mixed tumors (SE + NS) that has also been suggested by anecdotal evidence at the RNA and protein level [126].…”

IGF2 knockdown in two colorectal cancer cell lines decreases survival, adhesion and modulates survival-associated genes

“…Previously, micro-and tissue array analysis of a group of patients with testicular tumors allowed their subdivision into two groups, seminomatous and germinal tumors [45]. Increased levels of IGF2 expression were seen in the first group and correlated with increased JUP expression.…”

Recurrent seminomas: Clinical features and biologic implications

“…We also wished to test, as a pilot study, whether these tumors express any specific biomarkers that might distinguish them as a unique subtype of seminoma. Because of their visceral metastases, and according to some intriguing findings in the literature [8], we hypothesized that some atypical seminomas are biologically related to embryonal carcinomas.…”

“…In particular, 1 report noted that some seminomas exhibit a molecular profile that is more similar to that of embryonal carcinomas than it is to that of classic seminomas [8]. The markers that were used to distinguish between the seminomas in that microarray study included CD30.…”