Negative control—how hCG, and a failed experiment, changed my life

Abstract

My scientific career was going to be in cancer immunology and modulation of MHC antigen expression in urogenital tumors. This involved attending operations, collecting fresh tissue samples, and establishing primary cultures of the tumor cells. The tumors I attempted to culture included testicular germ cell tumors. These were a mixture of seminomas and nonseminomas with trophoblast differentiation. I was successful in propagating several testicular germ cell cultures through multiple passages. Knowing that the male patients, from which the tumors had been taken, had been serum positive for “hCG,” I harvested spent culture media from these testicular germ cell cultures and sent them to our partner laboratory for hCG immunoassay. Being a vigilante and well- trained young scientist, I also took spent culture media from bladder cancers I was growing at the same time to act as a negative control. The results came back from the clinical immunoassay laboratory as negative for any hCG in my testicular germ cell tumors. However, my controls were positive with significant amounts of hCG! This observation changed my entire life. I repeated the immunoassay experiments and conducted protein chemistry and molecular characterized that showed that in fact these bladder cancers were only producing the free beta-subunit of hCG. Clinical studies showed ectopic free hCGbeta expression can be detected in 30% -50% of all patients with common epithelial cancers. Further- more, such expression is associated with highly aggressive tumors that rapidly metastasize.

keywords: Apoptosis; Autocrine; Bladder cancer; Cancer biomarker; Ectopic hCG; Free beta hCG; Growth factor; hCG; Paracrine; Testicular cancer