Overexpression and amplification of Murine double minute 2 as a diagnostic tool in large lipomatous tumor and its correlation with Ki67 proliferation index: An institutional experience.

Context: Well-differentiated liposarcoma (WDLPS) is the most common type of liposarcoma and sometimes can be diffi cult to distinguish from large lipoma due to the similar morphology. Aims: This study proposed to evaluate the expression and amplifi cation of Murine double minute 2 (MDM2) gene and determine its correlation with Ki67 proliferation index. Settings and Design: This study used cross-sectional design. Materials and Methods: This study enrolled 37 cases of lipomatous tumors with >5 cm in size. Eighteen cases of WDLPS and 19 cases of lipoma were stained for MDM2 and Ki67 immunohistochemistry, followed by MDM2 in situ hybridization in 12 selected cases. Statistical Analysis Used: MDM2 overexpression and amplification status for both groups were compared using Chi-square test, with the alternative of Fisher’s exact test. Correlation test between MDM2 overexpression and clinical characteristics with the Ki67 proliferation index were performed using Pearson’s test with the alternative of Spearman’s rho test. Results: MDM2 overexpression was detected in all WDLPS cases and in 3 (16%) of lipoma cases with signifi cance difference (P = 0.000), whereas MDM2 amplifi cation was found in all WDLPS and in 1 of lipoma cases (P = 0.200). There was a strong correlation between MDM2 overexpression and higher Ki67 proliferation index (r = 0.645, P = 0.000). Conclusion: Evaluation of MDM2 overexpression can be used as a useful adjunct to differentiate WDLPS from large lipoma and seems to be related with Ki67 proliferation index.

Testosterone undecanoate and depo medroxyprogesterone acetate induced azoospermia through increased expression of spermatogenic cell caspase 3.

The administration of a combination of testosterone undecanoate (TU, a long-acting androgen) and depo-medroxyprogesterone acetate (DMPA) were investigated in term of suppression of rat sperm concentration in vivo to azoospermia through increasing activity of spermatogenic cell caspase 3. Adult Sprague Dawley rats received TU and DMPA of 2.5 mg and 1.25 mg, respectively, a regimen known to rapidly reduce intra testicular testosterone and to produce azoospermia within 12 weeks. Caspase 3 positive sperm cells increased compared with control levels during 6 weeks post-injection and increased further through 60 weeks. Immunohistochemistry for caspase 3 revealed that spermatocytes represented the predominant caspase 3 positive germ cells. Modest immunoreactivity for caspase-3 was localized to nuclear region of the germ cells of control and treated testes. Immunohistochemistry study revealed significantly increased caspase-3 expression in nuclei of germ cells during administration of TU+DMPA to rats. Additionally, the caspase 3 content was significantly increased in germ cells during rats were administered TU+DMPA (453.90±84.88 cells/200 seminiferous tubules) and caspase 3 significant increase in immunoreactivity was localized to the nuclei of spermatogonia, spermatocytes, and spermatids. Taken together, these results indicated that azoospermia due to reduced intratesticular testosterone concentration was caspase-3 activation dependent and suggested that the increase in active caspase-3 in the nucleus may be involved in the induction of decreased sperm production.