VARIABLE EXPRESSION OF HST-1, INT-2, AND PARATHYROID HORMONE-RELATED PROTEIN IN DIFFERENT HISTOLOGICAL TYPES OF HUMAN TESTICULAR GERM-CELL TUMORS

Some investigators have reported that certain proto-oncogene products play an important role in normal cellular growth and/or differentiatio n and in the response to proliferative signals. We have investigated 2 4 testicular germ cell tumors for the expression of hst-1, int-2, para thyroid hormone-related protein (PTHrP), Ki-ras and N-myc at the RNA l evels using Northern blot analysis. We also investigated PTHrP express ion immunohistochemically using a monoclonal anti-PTHrP antibody. Ther e was a significant difference in hst-1 expression between seminomas a nd nonseminomas, since expression was detected in 6 out of 8 (75%) non seminomas and only 1 out of 15 (7%) seminomas. No association was foun d between tumor stage and Ki-ras or N-myc expression, and no int-2 mRN A was detected in the germ cell tumors. PTHrP is one of the main facto rs of humoral hypercalcemia of malignancy. It was also recently found in normal human tissue and has been suggested to play an important rol e in the differentiation of keratinocytes, endocrine tissue, and extra embryonic elements. The immunohistochemical localization of PTHrP corr elated well with in situ hybridization and Northern blot findings. PTH rP was detected in all seminomas and in choriocarcinoma tumor elements of the mixed type, irrespective of the serum calcium level. In semino mas, PTHrP was expressed as the common form at the transcriptional lev el (1.4 and 2.2 kb by Northern blot analysis) and was characteristical ly located in the nucleus by immunostaining. The presence of PTHrP in choriocarcinoma tumor elements might reflect their functional and phen otypic similarity to placental tissue. PTHrP expression was not detect ed in embryonal carcinomas or teratomas. Thus, the phenotypic differen tiation of embryonic and extraembryonic elements seems to be unrelated to the expression and localization of PTHrP.