JAZF1/JJAZ1 gene fusion in endometrial stromal sarcomas: molecular analysis by reverse transcriptase-polymerase chain reaction optimized for paraffin-embedded tissue.

Endometrial stromal tumors are rare uterine neoplasms including benign stromal nodules, low-grade endometrial stromal sarcomas (ESS), and undifferentiated endometrial sarcomas (UES), the latter representing the most aggressive form. Morphological characteristics and cytogenetic abnormalities are heterogeneous, making diagnosis difficult. Recently, a gene fusion on chromosome 7 that includes two zinc-finger genes (JAZF1 and JJAZ1) has been discovered in these tumors. Hitherto only 31 cases, described by three different research groups, have shown JAZF1/JJAZ1 fusion in approximately 50% of all analyzed low-grade ESSs whereas it is less frequent in UESs. In this study we analyzed 20 ESS and 2 UES cases using two-step reverse transcriptase-polymerase chain reaction optimized for formalin-fixed, paraffin-embedded tissue. In our subset of samples, the JAZF1/JJAZ1 fusion transcript occurred in 80% of analyzed ESS cases and in none of two UES cases. In comparison to published data, our results identified the JAZF1/JJAZ1 gene fusion more frequently in endometrial stromal tumors than hitherto presumed. This cytogenetic abnormality was not present in normal endometria, leiomyomas, or leiomyosarcomas or in lung, gastric, or hepatic carcinomas, indicating its specificity for endometrial stromal tumors. In combination with other established methods, accurate reverse transcriptase-polymerase chain reaction analysis of JAZF1/JJAZ1 gene fusion may be useful in diagnosing difficult or unusual ESS/UES cases.

[1]  K. Zatloukal,et al.  Inverse correlation of secreted frizzled‐related protein 4 and β‐catenin expression in endometrial stromal sarcomas , 2004, The Journal of pathology.

[2]  J. L. Mansi,et al.  Endometrial stromal sarcomas. , 1990, Gynecologic oncology.

[3]  R. Sciot,et al.  Cytogenetics revealing the diagnosis in a metastatic endometrial stromal sarcoma. , 1996, Histopathology.

[4]  H. Taylor,et al.  Mesenchymal tumors of the uterus. I. A clinical and pathological study of 53 endometrial stromal tumors , 1966, Cancer.

[5]  M. Ladanyi,et al.  Molecular Detection of JAZF1-JJAZ1 Gene Fusion in Endometrial Stromal Neoplasms with Classic and Variant Histology: Evidence for Genetic Heterogeneity , 2004, The American journal of surgical pathology.

[6]  J. Sklar,et al.  Frequent fusion of the JAZF1 and JJAZ1 genes in endometrial stromal tumors , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[7]  F. Amant,et al.  The classification of a uterine sarcoma as 'high-grade endometrial stromal sarcoma' should be abandoned. , 2004, Gynecologic oncology.

[8]  K. Chang,et al.  Primary Uterine Endometrial Stromal Neoplasms: A Clinicopathologic Study of 117 Cases , 1990, The American journal of surgical pathology.

[9]  B. Bjerkehagen,et al.  Cytogenetic and molecular genetic analyses of endometrial stromal sarcoma: nonrandom involvement of chromosome arms 6p and 7p and confirmation of JAZF1/JJAZ1 gene fusion in t(7;17). , 2003, Cancer genetics and cytogenetics.

[10]  B. Quade,et al.  h-Caldesmon Expression Effectively Distinguishes Endometrial Stromal Tumors From Uterine Smooth Muscle Tumors , 2001, The American journal of surgical pathology.

[11]  K. Chang,et al.  Utility of CD10 in Distinguishing between Endometrial Stromal Sarcoma and Uterine Smooth Muscle Tumors: An Immunohistochemical Comparison of 34 Cases , 2001, Modern Pathology.

[12]  P. Neven,et al.  THE DIAGNOSTIC PROBLEM OF ENDOMETRIAL STROMAL SARCOMA: REPORT ON SIX CASES , 2003, International Journal of Gynecologic Cancer.

[13]  R. Soslow,et al.  h-Caldesmon, a Novel Smooth Muscle-Specific Antibody, Distinguishes Between Cellular Leiomyoma and Endometrial Stromal Sarcoma , 2001, The American journal of surgical pathology.

[14]  P. Clement,et al.  Endometrial Stromal Tumors: An Update on a Group of Tumors with a Protean Phenotype , 2000, Advances in anatomic pathology.

[15]  J. Bullerdiek,et al.  A third case of a low-grade endometrial stromal sarcoma with a t(7;17)(p14∼21;q11.2∼21) , 1997 .

[16]  H. van den Berghe,et al.  Endometrial stromal sarcoma t(7;17)(p15-21;q12-21) is a nonrandom chromosome change. , 1992, Cancer genetics and cytogenetics.

[17]  P. Maxwell,et al.  CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms , 2001, Histopathology.

[18]  P. Chu,et al.  Paraffin-section detection of CD10 in 505 nonhematopoietic neoplasms. Frequent expression in renal cell carcinoma and endometrial stromal sarcoma. , 2000, American journal of clinical pathology.