OCT4: biological functions and clinical applications as a marker of germ cell neoplasia

Germ cell tumours (GCTs) are a heterogeneous group of neoplasms, which develop in the
gonads as well as in extragonadal sites, that share morphological patterns and an overall
good prognosis, owing to their responsiveness to current surgical, chemotherapeutic,
and radiotherapeutic measures. GCTs demonstrate extremely interesting biological features
because of their close relationships with normal embryonal development as demonstrated
by the pluripotentiality of some undifferentiated GCT variants. The similarities between
GCTs and normal germ cell development have made it possible to identify possible pathogenetic
pathways in neoplastic transformation and progression of GCTs. Genotypic and
immunophenotypic profiles of these tumours are also useful in establishing and narrowing
the differential diagnosis in cases of suspected GCTs. Recently, OCT4 (also known as
OCT3 or POU5F1), a transcription factor that has been recognized as fundamental in the
maintenance of pluripotency in embryonic stem cells and primordial germ cells, has been
proposed as a useful marker for GCTs that exhibit features of pluripotentiality, specifically
seminoma/dysgerminoma/germinoma and embryonal carcinoma. The development
of commercially available OCT4-specific antibodies suitable for immunohistochemistry on
paraffin-embedded specimens has generated increasing numbers of reports of OCT4 expression
in a wide variety of gonadal and extragonadal GCTs. OCT4 immunostaining has been
shown to be a sensitive and specific marker for seminomatous/(dys)germinomatous tumours
and in embryonal carcinoma variants of non-seminomatous GCTs, whether in primary
gonadal or extragonadal sites or in metastatic lesions. Therefore, OCT4 immunohistochemistry
is an additional helpful marker both in the differential diagnosis of specific histological
subtypes of GCTs and in establishing a germ cell origin for some metastatic tumours of
uncertain primary. OCT4 expression has also been reported in pre-invasive conditions such
as intratubular germ cell neoplasia, unclassified (IGCNU) and the germ cell component
of gonadoblastoma. Additionally, OCT4 immunostaining shows promise as a useful tool in
managing patients known to be at high risk for the development of invasive GCTs.