Identification and Characterization of Two Novel Testicular Germ Cell Markers, Glut3 and cyclinA2.
Brooke E Lane, Sunita B Jones, James D Brooks, John Higgins. Stanford University School of Medicine, Palo Alto, CA
Background: Testicular germ cell tumors (TGCT) are the most common type of testicular tumor, and encompass different histologic types that carry great significance for prognosis and treatment. Though diagnoses are often made on hematoxylin and eosin (H&E) stained sections alone, immunohistochemical studies are often required for more accurate diagnosis and when these tumors present at extragonadal sites. Traditional markers for identifying and distinguishing testicular germ cell tumors include PLAP, CD117, AFP, and CD30. More recently, the addition of OCT4 and SALL4 have increased sensitivity on immunohistological detection of germ cell tumors. Despite these recent breakthroughs in TGCT immunohistochemistry, there is still the need for additional ancillary markers to add to the repertoire.
Design: We examined gene expression data from a previously published microarray study that compared normal testis mRNA expression to various testicular germ cell tumors. We also performed a search of the literature to identify less well characterized, putative markers. Glut3 and cyclinA2 expression was evaluated by immunohistochemistry using tissue microarrays (TMA).
Results: Of 66 seminomas included in the TMA, 64 (97%) showed positive nuclear staining for cyclinA2, and 58 (88%) were strongly positive. Strong positive staining for cyclinA2 was also seen in the spermatocytic seminoma. All twenty of the embryonal carcinomas stained positively with cyclinA2, and 19 of these (95%) displayed strong nuclear staining for cyclinA2. Twenty of 20 embryonal carcinomas stained for glut3 in a membranous pattern. Of 8 yolk sac tumors, 100% stained with glut3; and in all but one, the staining pattern was strong and diffuse. We evaluated glut3 and cyclinA2 staining on a general tumor array containing 486 samples representing 156 different tumors. CyclinA2 did stain a number of other tumor types, but the majority of these were weak or focal staining. Glut3 was positive only in a handful of other tumors, interestingly, most of these were of ovarian origin.
Conclusions: Glut3 is a sensitive (96%) and specific (92%) marker for embryonal carcinomas and yolk sac tumors. While cyclinA2 is a sensitive marker of seminomas and embryonal carcinomas (98%), its specificity is lower if focal and weak staining of non germ cell tumors is considered positive. The sensitivity and specificity of Glut3 are comparable to that seen for SALL4.
Category: Genitourinary (including renal tumors)
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 81, Tuesday Afternoon